Naringin exerts antiarrhythmic effects by inhibiting channel currents in mouse cardiomyocytes.

INTRODUCTION: Naringin, a flavonoid extracted from citrus plants, has a variety of biological effects. Studies have shown that increasing the consumption of flavonoid-rich foods can reduce the incidence of cardiac arrhythmia. Naringin has been reported to have beneficial cardiovascular effects and thus can be used to prevent cardiovascular diseases, but the electrophysiological mechanism through which it prevents arrhythmias has not been elucidated. This study was conducted to investigate the effect of naringin on the transmembrane ion channel currents in mouse ventricular myocytes and the antiarrhythmic effect of this compound on Langendorff-perfused mouse hearts. METHODS: Action potentials (APs) and ionic currents were recorded in isolated ventricular myocytes using the whole-cell patch-clamp technique. Anemone toxin II (ATX II) and CaCl2 were used to induce early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs), respectively. Electrocardiogram (ECG) recordings were conducted in Langendorff-perfused mouse hearts with a BL-420F biological signal acquisition and analysis system. RESULTS: At the cellular level, naringin shortened the action potential duration (APD) of ventricular myocytes and decreased the maximum depolarization velocity (Vmax) of APs.Naringin inhibited the L-type calcium current (ICa.L) and ATX II enhanced the late sodium current (INa.L) in a concentration-dependent manner with IC50 values of 508.5 µmol/L (n = 9) and 311.6 µmol/L (n = 10), respectively. In addition, naringin also inhibited the peak sodium current (INa·P) and delayed the rectifier potassium current (IK) and the transient outward potassium current (Ito). Moreover, naringin reduced ATX II-induced APD prolongation and EADs and had a significant inhibitory effect on CaCl2-induced DADs as well. At the organ level, naringin reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) induced by ATX II and shortened the duration of both in isolated hearts. CONCLUSION: Naringin can inhibit the occurrence of EADs and DADs at the cellular level; furthermore, it can inhibit INa.L, ICa.L, INa·P, IK, and Ito in ventricular myocytes. Naringin also inhibits arrhythmias induced by ATX II in hearts. By investigating naringin with this electrophysiological method for the first time, we determined that this flavonoid may be a multichannel blocker with antiarrhythmic effects.

Fibrous hamartoma of infancy with bone destruction of the tibia: A case report.

BACKGROUND: Fibrous hamartoma of infancy (FHI) is a rare disease of infancy with unknown etiology. The disease mainly involves soft tissue, has no specific clinical manifestations, and is difficult to diagnose. At present, the diagnosis is mainly confirmed by histopathological examination, and the main treatment is surgical resection of the pathological tissue, which is prone to recurrence. CASE SUMMARY: A five-month-old female patient was admitted to our hospital with swelling in the right calf. Two biopsies were performed in our hospital and another hospital, respectively, confirming the diagnosis as fibrous hamartoma. After exclusion of surgical contraindications, resection was performed with clear margins of 1 cm. Radiographic examination showed tumor recurrence more than four months after the operation, and surgery was performed again to extend the resection margins to 1.5 cm. The patient is recovering well, and after a follow-up of 36 mo, shows no signs of recurrence. CONCLUSION: Our case report demonstrates that FHI should be considered in the differential diagnosis for a lower extremity mass with bone destruction. For FHI with bone destruction and unclear boundaries, excision margins of 1.5 cm could be superior to margins of 1 cm.

[Pollution Characteristics and Emission Factors of PCDD/Fs from Iron and Steel Industry].

The pollution level, emission characteristics, and emission factors of PCDD/Fs from a number of steel plants were investigated in a particular province of China. The results showed that the concentration of PCDD/Fs was at a low level and decreased by 1-2 orders of magnitude compared with that in 2005-2019. In detail, the concentrations of PCDD/Fs ranged from 0.003-0.557 ng·m-3(I-TEQ), and the mean value was 0.165 ng·m-3 for the sintering process. Moreover, the concentrations of PCDD/Fs ranged from 0.006 to 0.057 ng·m-3, and the mean value was 0.025 ng·m-3 for the electric furnace process. In addition, the concentration of PCDD/Fs in the iron and steel industry from 2005 to 2020 increased first and then decreased, especially after the implementation of the new emission standard and the ultra-low emission control of conventional pollutants such as smoke, showing a significant decline. The results of fingerprint analysis showed that 2,3,7,8-TCDF was the largest congener contributing to the mass concentration, and lower chlorinated PCDFs were increased. This result differed from those of previous studies in which highly chlorinated PCDFs and PCDDs dominated, indicating that the generation source of PCDD/Fs had changed. The congener and isomer profiles of PCDD/Fs in flue gas from the sintering process were similar to those in the flue gas from the electric furnace process. Additionally, showing the characteristics of the typical high-temperature thermal process, the de novo synthesis may be the dominant mechanism of formation of PCDD/Fs in the sintering process and electric furnace process. The emission factor was 0.003-0.5 µg·t-1 (I-TEQ), and the average emission factor was (0.18±0.22) µg·t-1 for the sintering process. The emission factor was 0.04-0.5 µg·t-1, and the average emission factor was (0.27±0.23) µg·t-1 for the electric furnace process. These values were far lower than those of the standard toolkit for identification and quantification of dioxin and furan emissions released by UNEP in 2013 and the emission factors in the dioxin emission inventory of China in 2004. It is suggested that the emission factors of PCDD/Fs in the iron and steel industry of China should be studied and updated.

ED50 and ED95 of propofol combined with different doses of esketamine for children undergoing upper gastrointestinal endoscopy: A prospective dose-finding study using up-and-down sequential allocation method.

WHAT IS KNOWN AND OBJECTIVE: Propofol and esketamine are routine anaesthetics used in sedation or general anaesthesia for paediatric procedures. Coadministration could reduce the dose of either propofol or esketamine required and lower the incidence of drug-related adverse events. We designed a four-arm randomized controlled trial in children undergoing diagnostic upper gastrointestinal endoscopy to investigate the dose of propofol with different doses of esketamine inducing appropriate depth of anaesthesia in 50% patients (median effective dose, ED50 ). METHODS: After getting the approval of the research ethics committee and informed consent, 92 paediatric patients planning for upper gastrointestinal endoscopy were divided into four groups randomly: esketamine 0, 0.25, 0.5 and 1 mg/kg groups (n = 23/group). Propofol doses followed the Dixon and Massey up-and-down method with different starting and interval doses between groups. During the first attempt of endoscope insertion, if patients' reactions prevented the insertion, it would be considered as a failure. The awakening time, total propofol doses, as well as the perioperative and post-procedure adverse events were evaluated and recorded for each patient. RESULTS AND DISCUSSION: The ED50 (median, 95% confidence interval) of propofol was significantly greater in esketamine 0 and 0.25 mg/kg groups in comparison with the esketamine 0.5 and 1 mg/kg groups (4.1 [3.3-4.9]; 3.1 [2.5-3.8] mg/kg vs. 1.8 [1.1-2.4]; 0.8 [0.2-1.3] mg/kg, respectively, p < .05). The total doses of propofol in esketamine 0.5 and 1 mg/kg groups were statistically lower than these in esketamine 0 and 0.25 mg/kg group (p < .01). The mean blood pressure was lower in the esketamine 0 mg/kg group than that in 1 mg/kg group after administration and during the procedure (p < .01). The esketamine 1 mg/kg group showed a higher incidence of vomiting and visual disturbances than the other three groups (p < .001). WHAT IS NEW AND CONCLUSION: In children who accomplished diagnostic paediatric upper gastrointestinal endoscopy under deep sedation/anaesthesia, the total dosage of propofol needed was reduced significantly in esketamine 0.5 and 1 mg/kg groups with a corresponding reduce in propofol-related hemodynamic changes. However, a higher incidence of esketamine-related adverse effects was found in esketamine 1 mg/kg group.

Inhibition of Ca2+-dependent protein kinase C rescues high calcium-induced pro-arrhythmogenic cardiac alternans in rabbit hearts.

Cardiac alternans closely linked to calcium dysregulation is a crucial risk factor for fatal arrhythmia causing especially sudden death. Calcium overload is well-known to activate Ca2+-dependent protein kinase C (PKC); however, the effects of PKC on arrhythmogenic cardiac alternans have not yet been investigated. This study aimed to determine the contributions of PKC activities in cardiac alternans associated with calcium cycling disturbances. In the present study, action potential duration alternans (APD-ALT) induced by high free intracellular calcium ([Ca2+]i) exerted not only in a calcium concentration-dependent manner but also in a frequency-dependent manner. High [Ca2+]i-induced APD-ALT was suppressed by not only BAPTA-AM but also nifedipine. On the other hand, PKC inhibitors BIM and Gö 6976 eliminated high [Ca2+]i-induced APD-ALT, and PKC activator PMA was found to induce APD-ALT at normal [Ca2+]i condition. Furthermore, BIM effectively prevented calcium transient alternans (CaT-ALT) and even CaT disorders caused by calcium overload. Moreover, BIM not only eliminated electrocardiographic T-wave alternans (TWA) caused by calcium dysregulation, but also lowered the incidence of ventricular arrhythmias in isolated hearts. What's more, BIM prevented the expression of PKC α upregulated by calcium overload in high calcium-perfused hearts. We firstly found that pharmacologically inhibiting Ca2+-dependent PKC over-activation suppressed high [Ca2+]i-induced cardiac alternans. This recognition indicates that inhibition of PKC activities may become a therapeutic target for the prevention of pro-arrhythmogenic cardiac alternans associated with calcium dysregulation.

Ketogenic diet-mediated steroid metabolism reprogramming improves the immune microenvironment and myelin growth in spinal cord injury rats according to gene and co-expression network analyses.

The ketogenic diet has been widely used in the treatment of various nervous system and metabolic-related diseases. Our previous research found that a ketogenic diet exerts a protective effect and promotes functional recovery after spinal cord injury. However, the mechanism of action is still unclear. In this study, different dietary feeding methods were used, and myelin expression and gene level changes were detected among different groups. We established 15 RNA-seq cDNA libraries from among 4 different groups. First, KEGG pathway enrichment of upregulated differentially expressed genes and gene set enrichment analysis of the ketogenic diet and normal diet groups indicated that a ketogenic diet significantly improved the steroid anabolic pathway in rats with spinal cord injury. Through cluster analysis, protein-protein interaction analysis and visualization of iPath metabolic pathways, it was determined that Sqle, Sc5d, Cyp51, Dhcr24, Msmo1, Hsd17b7, and Fdft1 expression changed significantly. Second, through weighted gene co-expression network analysis showed that rats fed a ketogenic diet showed a significant reduction in the expression of genes involved in immune-related pathways, including those associated with immunity and infectious diseases. A ketogenic diet may improve the immune microenvironment and myelin growth in rats with spinal cord injury through reprogramming of steroid metabolism.

Relationships Between Anxiety Symptoms, Hopelessness and Suicidal Ideation Among Parental Caregivers of Mandarin-Speaking Children With Speech Impairment: The Mediating Effect of Depressive Symptoms.

Background: Determining the mental health status of parents who chronically care for a child with speech impairment is important for developing appropriate interventions to improve both parents' and children's health and achieve a win-win situation. Unfortunately, no study in China has explored this issue. This study investigated the differences in four aspects of mental health between maternal and paternal caregivers for the Mandarin-speaking children with speech impairment and determine whether depressive symptoms mediate the relationships between anxiety symptoms and suicidal ideation, hopelessness and suicidal ideation. Methods: This cross-sectional questionnaire survey was conducted in February 2020 by sending a link to the predesigned electronic questionnaire in WeChat. Standardized assessment tools were employed. Hierarchical multiple logistic regression was conducted to examine the associations between various factors and suicidal ideation, and two separate structural equation models were performed to evaluate the mediating effects of depressive symptoms in the relationship between anxiety symptoms and suicidal ideation as well as between hopelessness and suicidal ideation. Results: This study included 446 parental caregivers of Mandarin-speaking children with speech impairment. Paternal caregivers had greater score than maternal caregivers on loss of motivation (one of the subdomains of hopelessness). Somatic complications of the child (OR = 2.73, 95% CI: 1.09-6.67) and depressive symptoms (OR = 3.38, 95% CI: 1.83-6.30) were positively associated with caregivers' suicidal ideation. Having speech therapy of child (OR = 0.54, 95% CI: 0.29-0.98) was negatively correlated with caregivers' suicidal ideation. There was direct effect of depressive symptoms on suicidal ideation. Depressive symptoms play mediating roles on the relationships between anxiety symptoms (ß = 0.171, p < 0.001) as well as between hopelessness and suicidal ideation (ß = 0.187, p < 0.001). Conclusions: Paternal and maternal caregivers of Mandarin-speaking children with speech impairment suffered from mental health problems. Preventive strategies and interventions to ameliorate parental psychological well-being, and health care policies to increase the accessibility to speech therapy care of children with speech impairment are imperative.

[Characteristics of Sludge and Associated Risk Assessment of Urban Sewage Treatment Plants].

In urban solid waste management, the scientific and reasonable disposal and utilization of sewage sludge is becoming more and more important. It can be said that the pollution status and chemical properties of sewage sludge in urban sewage treatment plants can provide a basis for the scientific disposal and utilization of sludge. In this study, the characteristics of pH, moisture content, Cd, Cr, Cu, Zn, Pb, As, Hg, Ni, mineral oil, volatile phenol, PAHs, organic matter, nitrogen, phosphorus, and potassium were evaluated in sewage sludge collected from 49 sewage treatment plants in a certain city. The pollution status of heavy metals and organic pollutants, the frequency distribution of pollutant concentrations, and changes in the nutrient content were analyzed. The Nemero index and Hakanson potential ecological hazard index were used to assess the potential ecological risks of heavy metals in the agricultural utilization process of sludge. The results showed that under the condition of neutral pH values and high moisture content, the order of heavy metal content was Zn > Cu > Cr > Pb > Ni > As > Hg > Cd. The principal component analysis (PCA) results indicated that Cd, Pb, Hg, Ni, and As constituted the main load factors of the first main component of heavy metal sources. The most concentrated contents of 8 heavy metal frequency distributions among the 49 samples were 38.9-1380.0, 62.6-182.7, 63.6-181.3, 0.0-97.8, 19.3-68.4, 0.8-29.2, 0.3-8.7, and 0.01-0.96 mg·kg-1. In addition, the most concentrated frequency distribution of mineral oil, volatile phenol, and PAH concentration were 87.0%, 87.9%, and 77.6%, respectively. Moreover, the nutrient content of sludge was higher than the average level in China, and the organic matter content was 67.4%, 75.9%, and 92.5% of that of pig manure, cow dung, and chicken manure, while the content of nitrogen, phosphorus, and potassium was not very different. The Nemero index and Hakanson ecological hazard index results showed that the sludge of urban sewage treatment plant in the city has certain ecological risks. However, four sewage treatment plants were heavily polluted or highly ecologically hazardous among the 44 plants in this study, which were in line with the Standards for pollutant control of agricultural sludge. In summary, there are certain potential ecological risks for the agricultural utilization of sludge in the city, and it is necessary to reduce the heavy metal content before resourcing. More importantly, on the premise that the sludge meets the agricultural standards, a comprehensive ecological risk assessment is required to select a reasonable sludge recycling method.

[VOCs Removal and Emission Monitoring of Beijing Bulk Gasoline Terminals in 2012-2019].

Bulk gasoline terminals are an important emission source of volatile organic compounds (VOCs) in cities. Beijing started to promote the installation of oil and gas recovery devices at oil storage terminals in 2006 to reduce VOCs emissions, since then VOCs emissions from the terminals have been monitored by the municipal government every year. This paper analyzes the VOCs emission characteristics of oil storage terminals in Beijing from 2012 to 2019. We found that the VOCs import concentration was 165.3 g·m-3 in 2019 and had experienced a decline-rise-decline pattern during 2012-2019. The emission concentration was 7.3 g·m-3 in 2019 and had declined continuously during the preceding eight years. The removal efficiency of VOCs of the gas recovery devices tended to be stable and ranged from 45.5% to 100%. Although the emission concentration had decreased significantly, the removal efficiency of the recovery unit at the oil storage terminals had decreased. Therefore, this paper proposed to strengthen process management, the inspection of the service life of the oil and gas recovery units, and check and maintain records. In addition, the removal efficiency index should be included in the scope of law enforcement and "double index" requirements should be implemented This paper will provide a scientific basis for the future development of atmospheric improvement measures.

Reprogramming immunosuppressive myeloid cells by activated T cells promotes the response to anti-PD-1 therapy in colorectal cancer.

Overcoming local immunosuppression is critical for immunotherapy to produce robust anti-tumor responses. Myeloid-derived suppressor cells (MDSCs) are key regulators of immunosuppressive networks and promote tumor progression. However, it remains unclear whether and how tumor-infiltrating MDSCs are shaped in response to anti-PD-1 treatment and what their impact on therapeutic efficacy is in colorectal cancer (CRC). In this study, the levels of infiltrating MDSCs were significantly higher in the non-responding organoids and were selectively reduced in the responding group, with MDSCs showing increased apoptosis and attenuated functional activity after anti-PD-1 treatment. A negative correlation between T-cell activation and MDSC function was also observed in fresh human CRC tissues. Mechanistic studies revealed that autocrine IFN-α/ß upregulated TRAIL expression on activated T cells to elicit MDSC apoptosis via the TRAIL-DR5 interaction and acted synergistically with TNF-α to inhibit MDSC function of suppressing the T-cell response through the JNK-NMDAR-ARG-1 pathway. Moreover, blockade of IFN-α/ß and TNF-α abolished the therapeutic efficacy of anti-PD-1 treatment by preserving the frequency and suppressive activity of infiltrating MDSCs in a CRC mouse model. This result suggested that reprogramming MDSCs by IFN-α/ß and TNF-α from activated T cells was necessary for successful anti-PD-1 treatment and might serve as a novel strategy to improve the response and efficacy of anticancer therapy.

Metabolites in the TCA Cycle Promote Resistance to Chloramphenicol of Edwardsiella tarda.

Antibiotic-resistant bacteria are a serious threat to human and animal health. Metabolite-enabled eradication of drug-resistant pathogens is an attractive strategy, and metabolite adjuvants, such as fumarate, are used for restoring the bactericidal ability of antibiotics. However, we show that metabolites in the TCA cycle increase the viability of Edwardsiella tarda against chloramphenicol (CAP), based on the survival assay of differential metabolites identified by LC-MS/MS. Furthermore, NADPH promotes CAP resistance in the CAP-resistant strain, while oxidants restore the bactericidal ability. Finally, we show that the intracellular redox state determines the sensitivity to CAP, and the total antioxidative capacity is decreased significantly in the antibiotic-resistant strain. Considering that the metabolites promote CAP resistance, metabolite adjuvants should be applied very cautiously. Overall, our research expands on the knowledge that the redox state is related to the bactericidal ability of CAP.

Retinoic Acid Synthesis Deficiency Fosters the Generation of Polymorphonuclear Myeloid-Derived Suppressor Cells in Colorectal Cancer.

Metabolism is reprogrammed in cancer to fulfill the demands of malignant cells for cancer initiation and progression. Apart from its effects within cancer cells, little is known about whether and how reprogramed metabolism regulates the surrounding tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSC) are key regulators of the TME and greatly affect tumor progression and therapeutic responses. In this study, our results revealed that retinol metabolism-related genes and enzymes were significantly downregulated in human colorectal cancer compared with adjacent colonic tissues, and tumors exhibited a defect in retinoic acid (RA) synthesis. Reduced ADH1-mediated retinol metabolism was associated with attenuated RA signaling and accumulated MDSCs in colorectal cancer tumors. Using an in vitro model, generating MDSCs from CD34+ myeloid precursors, we found that exogenous RA could abrogate the generation of polymorphonuclear MDSCs (PMN-MDSC) with negligible impact on myeloid differentiation. Mechanistically, RA could restrain the glycolytic capacity of myeloid cells, which in turn activated the AMP-activated protein kinase (AMPK) pathway, further impairing the suppressive capacity of myeloid cells. Supplementation with RA could significantly delay tumor growth, with reduced arginase-1-expressing myeloid cells and increased CD8+ and granzyme B+ T cells in both colitis-associated and implanted MC38 mouse colorectal cancer models. Our results indicated that the defect in ADH1-mediated RA synthesis could provide a possible mechanism that fosters the generation of PMN-MDSCs in colorectal cancer and that restoring RA signaling in the TME could serve as a promising therapeutic strategy to abrogate the generation of PMN-MDSCs.

α-Synuclein in traumatic and vascular diseases of the central nervous system.

α-Synuclein (α-Syn) is a small, soluble, disordered protein that is widely expressed in the nervous system. Although its physiological functions are not yet fully understood, it is mainly involved in synaptic vesicle transport, neurotransmitter synthesis and release, cell membrane homeostasis, lipid synthesis, mitochondrial and lysosomal activities, and heavy metal removal. The complex and inconsistent pathological manifestations of α-Syn are attributed to its structural instability, mutational complexity, misfolding, and diverse posttranslational modifications. These effects trigger mitochondrial dysfunction, oxidative stress, and neuroinflammatory responses, resulting in neuronal death and neurodegeneration. Several recent studies have discovered the pathogenic roles of α-Syn in traumatic and vascular central nervous system diseases, such as traumatic spinal cord injury, brain injury, and stroke, and in aggravating the processes of neurodegeneration. This review aims to highlight the structural and pathophysiological changes in α-Syn and its mechanism of action in traumatic and vascular diseases of the central nervous system.

Effect of recorded maternal voice on emergence agitation in children undergoing bilateral ophthalmic surgery: A randomised controlled trial.

AIM: This study was designed to investigate whether the playing-back of the recorded maternal voice through the headphones to children undergoing bilateral ophthalmic surgery has clinical effects on the incidence of emergence agitation, and the anaesthesia recovery course. METHODS: In this prospective, blinded and randomised study, 127 children, aged 2-8 years and undergoing bilateral ophthalmic surgery were randomly allocated to one of the two groups: group T (treatment group, listening to recorded mother's voice via headphones) or group C (control group, wearing headphones without auditory stimuli). The primary outcome was the incidence of emergence agitation, and the secondary outcomes were the awakening time, and the post-anaesthesia care unit (PACU) stay time. RESULTS: Children in the group of listening recorded mother's voice exhibited significantly low incidence of emergence agitation compared with those in the control group (32.8 vs. 55.6%; odds ratio (95% confidence interval): 0.39(0.19-0.80); P = 0.010). The awakening time was shorter in group T as compared to that in group C (22.9 (10.4) vs. 27.3 (13.7); P = 0.048). As results, the group T had significantly less PACU stay time with early discharge than the group C did (29.7 (12.1) vs. 34.8 (14.1); P = 0.031). CONCLUSIONS: Recorded mother's voice is an efficient method to reduce emergence agitation in children undergoing bilateral ophthalmic surgery with sevoflurane anaesthesia. Also, patients woke faster and PACU stay time was shorter in the mother's voice group as compared with the control group.

Osteocyte-derived exosomes induced by mechanical strain promote human periodontal ligament stem cell proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway.

BACKGROUND: The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal tissue homeostasis, and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells play crucial roles in responding to these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a means of cell-cell and cell-matrix communication in biological processes. METHODS: Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red, and ALP staining to evaluate the functions of exosomes induced by a mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, real-time PCR, FISH, luciferase reporter assay, and western blotting assay were used to investigate the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway. RESULTS: In this study, the exosomes secreted by MLO-Y4 cells exposed to mechanical strain (Exosome-MS) contributed to HPDLSC proliferation and osteogenic differentiation. High-throughput miRNA sequencing showed that miR181b-5p was upregulated in Exosome-MS compared to the exosomes derived from MLO-Y4 cells lacking mechanical strain. The luciferase reporter assay demonstrated that miR-181b-5p may target phosphatase tension homolog deletion (PTEN). In addition, PTEN was negatively regulated by overexpressing miR-181b-5p. Real-time PCR and western blotting assay verified that miR-181b-5p enhanced the protein kinase B (PKB, also known as AKT) activity and improved downstream factor transcription. Furthermore, miR-181b-5p effectively ameliorated the inhibition of HPDLSC proliferation and promoted HPDLSC induced by inflammation. CONCLUSIONS: This study concluded that exosomes induced by mechanical strain promote HPDLSC proliferation via the miR-181b-5p/PTEN/AKT signaling pathway and promote HPDLSC osteogenic differentiation by BMP2/Runx2, suggesting a potential mechanism for maintaining periodontal homeostasis.

Receptive and Expressive Vocabulary Skills and Their Correlates in Mandarin-Speaking Infants with Unrepaired Cleft Lip and/or Palate.

BACKGROUND: Vocabulary skills in infants with cleft lip and/or palate (CL/P) are related to various factors. They remain underexplored among Mandarin-speaking infants with CL/P. This study identified receptive and expressive vocabulary skills among Mandarin-speaking infants with unrepaired CL/P prior to cleft palate surgery and their associated factors. METHODS: This is a cross-sectional study involving patients at the Cleft Lip and Palate Center of the Stomatological Hospital of Xi'an Jiaotong University between July 2017 and December 2018. The Putonghua Communicative Development Inventories-Short Form (PCDI-SF) was used to assess early vocabulary skills. RESULTS: A total of 134 children aged 9-16 months prior to cleft palate surgery were included in the study. The prevalences of delays in receptive and expressive vocabulary skills were 72.39% (95% CI: 64.00-79.76%) and 85.07% (95% CI: 77.89-90.64%), respectively. Multiple logistic regression identified that children aged 11-13 months (OR = 6.46, 95% CI: 1.76-23.76) and 14-16 months (OR = 24.32, 95% CI: 3.86-153.05), and those with hard/soft cleft palate and soft cleft palate (HSCP/SCP) (OR = 5.63, 95% CI: 1.02-31.01) were more likely to be delayed in receptive vocabulary skills. CONCLUSIONS: Delays in vocabulary skills were common among Mandarin-speaking CL/P infants, and age was positively associated with impaired and lagging vocabulary skills. The findings suggest the necessity and importance of early and effective identification of CL/P, and early intervention programs and effective treatment are recommended for Chinese CL/P infants.

Conventional Ultrasound and Contrast-Enhanced Ultrasound in the Diagnosis of Splenic Diseases: A Systematic Review and Meta-analysis.

Accurate diagnosis of splenic diseases is important for timely and accurate treatment. The objective of this study was to compare the accuracy of contrast-enhanced ultrasound (CEUS) and conventional ultrasound (US) in detecting splenic lesions. A systematic literature search was undertaken, and 8 studies met the inclusion criteria. The sensitivity and specificity of the consolidated results of CEUS were 0.95 (95% confidence interval [CI], 0.92-0.97) and 0.97 (95% CI, 0.90-0.99), respectively (I2 = 27.4%; area under the curve [AUC] from a summary receiver operating characteristic curve = 0.97). The sensitivity and specificity of the consolidated results of conventional US were 0.70 (95% CI, 0.56-0.80) and 0.96 (95% CI, 0.76-0.99; I2 = 83.4%; AUC = 0.84). In this systematic review and meta-analysis, the sensitivity and specificity of CEUS were higher than those of conventional US in diagnosing splenic lesions. Contrast-enhanced US is a promising method for accurately diagnosing splenic lesions.

Glutamine Deprivation Promotes the Generation and Mobilization of MDSCs by Enhancing Expression of G-CSF and GM-CSF.

Solid tumors are often challenged by hypoxic and nutrient-deprived tumor microenvironments (TME) as tumors progress, due to limited perfusion and rapid nutrient consumption. While cancer cells can demonstrate the ability to survive in nutrient-deprived conditions through multiple intrinsic alterations, it is poorly understood how nutrient-deprived cancer cells co-opt the TME to promote cancer cell survival and tumor progression. In the present study, we found that glutamine deprivation markedly potentiated the expression of G-CSF and GM-CSF in mouse mammary cancer cells. The IRE1α-JNK pathway, which is activated by glutamine starvation, was found to be important for the upregulation of these cytokines. G-CSF and GM-CSF are well-known facilitators of myelopoiesis and mobilization of hematopoietic progenitor cells (HPC). Consistently, as tumors progressed, we found that several myeloid HPC compartments were gradually decreased in the bone marrow but were significantly increased in the spleen. Mechanistically, the HPC-maintaining capacity of the bone marrow was significantly impaired in tumor-bearing mice, with lower expression of HPC maintaining genes (i.e., CXCL12, SCF, ANGPT1, and VCAM1), and reduced levels of mesenchymal stem cells and CXCL12-producing cells. Furthermore, the mobilized HPCs that displayed the capacity for myelopoiesis were also found to accumulate in tumor tissue. Tumor-infiltrating HPCs were highly proliferative and served as important sources of immunosuppressive myeloid-derived suppressor cells (MDSCs) in the TME. Our work has identified an important role for glutamine starvation in regulating the expression of G-CSF and GM-CSF, and in facilitating the generation of immunosuppressive MDSCs in breast cancer.

Transcriptomic analysis of α-synuclein knockdown after T3 spinal cord injury in rats.

BACKGROUND: Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. RESULT: The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion (LV_SCI group). The results of the RNA-seq analysis showed that there were 337 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 153 DEGs specific to LV_SCI between the (SCI vs LV_SCI) and (SCI vs CON) comparisons. The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly upregulated the cholinergic synaptic & nicotine addiction and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis and RT-qPCR results showed that Chrm2 and Chrnb2 together significantly in both pathways. The proliferation of muscarinic cholinergic receptor subtype 2 (Chrm2) and nicotinic cholinergic receptor subtype ß2 (Chrnb2), and the neurogenesis were elevated in the injury site of LV_SCI group by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane. CONCLUSION: Knockdown of α-Syn after SCI enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-Syn on SCI but also helps to guide the treatment strategy for SCI.

miR­128 is upregulated in epilepsy and promotes apoptosis through the SIRT1 cascade.

The present study aimed to examine the functional and molecular effects of miR­128 in epilepsy, in order to investigate its potential protective mechanisms. Firstly, miR­128 expression in rats with lithium chloride­induced epilepsy was demonstrated to be increased compared with the control rats. Subsequently, results from an in vitro epilepsy model demonstrated that overexpression of miR­128 promoted nerve cell apoptosis, increased the protein expression of tumor protein p53, BCL2 associated X (Bax) and Cytochrome c, and enhanced caspase­3/9 activity, whereas it suppressed the protein expression of sirtuin 1 (SIRT1). In addition, these alterations may be reversed by the downregulation of miR­128. Furthermore, treatment with CAY10602, a SIRT1 agonist, reduced the effects of miR­128 on nerve cells in vitro. Treatment with pifithrin­ß hydrobromide, a p53 inhibitor, was additionally able to mitigate the effects of miR­128 in vitro. In conclusion, the present findings indicated that anti­miR­128 may exert neuroprotective effects in epilepsy, through the SIRT1/p53/Bax/Cytochrome c/caspase signaling pathway.