Search

Background: Anorectal malformations (ARMs) are common neonatal congenital anomalies. The prognosis of ARM patients is highly variable, and the condition itself can exert substantial psychological burdens on the parents. Thus, it is of paramount importance to raise awareness about the disease and appropriate management. Objectives: To characterize the spectrum of clinical presentation and outcome of ARMs. Methods: The present retrospective study retrieved the records of patients with ARMs admitted at a teaching hospital in Taichung City, Taiwan, between January 1, 2010, and December 31, 2019. Results: Seven children (two were males [28.57%]) with ARMs were included. Of them, three and four patients had high (42.86%) and low (57.14%) defects, respectively. Four patients (57%) had associated congenital heart disease and urogenital anomalies, and two patients (28.57%) had developmental delays. Constipation was the main clinical presentation (100%). Overall, there were no associations between gestational age, delivery modes, birth weight, associated cardiac and urogenital anomalies, constipation, body weight

ObjectiveTo examine the status and influencing factors of accessibility to immediate reimbursement for cross-provincial healthcare among rural residents and to provide evidence for improving related policies. Methods With simple random sampling, a nationwide online questionnaire survey was conducted among 2 497 rural residents having cross-provincial hospitalization during past one year in 100 designated hospitals providing healthcare service to non-local residents and with leading amount of immediate reimbursement for the services from September 2019 through September 2020. Macro- and micro-factors affecting the accessibility of immediate reimbursement for cross-provincial healthcare of rural residents were analyzed using hierarchical model. Results Of the 2 363 participants with valid responses, only 19.2% (n = 454) received cross-provincial immediate reimbursement for their out-of-pocket medical costs; the ratio of receiving cross-provincial immediate reimbursement was the highest among the participants with severe disease referrals (31.7% [152/480]) and cross-provincial medication in tertiary hospitals (21.0% [351/1 674]). For the participants with long-term living/working in non-home provinces, the probability of receiving immediate reimbursement for cross-provincial healthcare was only 25.4%/54.5% of that for the participants with severe disease referrals; for the participants having the cross-provincial healthcare in secondary hospitals, the probability was 64.4% of that for the participants having the healthcare in tertiary hospitals. Each 1% increase in the proportion of designated hospitals with immediate reimbursement for cross-provincial healthcare against all hospitals in a region is associated with a 36.8% increase in the probability of immediate reimbursement for cross-provincial healthcare among rural residents. Conclusion The accessibility to immediate reimbursement for cross-provincial healthcare among rural residents is poor probably due to the gap between cross-provincial healthcare and the coverage of immediate reimbursement network and due to the restriction of the rural residents' migration. The results suggest that targeted strategies need to be developed to increase the accessibility.

Abstract Background Major depressive disorder is characterized by not only monoamine neurotransmitters deficiencies but also persistent neuroinflammation. The complement system is an attractive therapeutic target for various inflammation-related diseases due to its early activation in inflammatory processes. Results In the present study, the dynamic alteration of complement C3 and its receptor C3aR during the occurrence of depression and the mechanism of astrocyte-microglia IL-1R/C3/C3aR on synaptic pruning were investigated. The proteomic analysis firstly showed that chronic stress caused an elevation of C3. GO analysis indicated that complement system-mediated synaptic pruning signaling was involved in depression. The dynamic observation indicated that C3/C3aR was activated in the early onset and throughout the course of depression induced by lipopolysaccharide (LPS) and chronic stress. In contrast, C3aR blockade inhibited the hyperactivation of microglial APT2/DHHC7 palmitoylation cycle, which mediated the translocation of STAT3 and the expression of proinflammatory cytokines. Meanwhile, C3aR blockade also attenuated the synaptic pruning and enhanced the synaptogenesis in the prefrontal cortex of mice. Moreover, the blockade of IL-1R/NF-κB signaling pathway reduced the release of C3 from astrocyte. Conclusions The current study demonstrates that astrocyte-microglia IL-1R/C3/C3aR activation causes the abnormal synaptic pruning in depression, and suggests that the activation of complement C3/C3aR may be particularly helpful in predicting the onset stage of depression.

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

Lagotis brachystachya Maxim, a common herb in Tibetan medicine, is mainly used to treat pneumonia, hepatitis, yellow water disease (gouty arthritis). Since long-term heavy drinking is also a risk factor for gouty arthritis, the present study aimed to evaluate the underlying protective role and mechanism of extracts of Lagotis brachystachya (ELB) in chronic alcoholic liver injury combined with gouty arthritis. The rat chronic alcoholic liver injury combined with gouty arthritis model was established by long-term alcohol consumption and monosodium urate (MSU) injection. The therapeutical action of ELB was then evaluated by biochemical measurement, histopathological examination, ankle swelling assessment, and protein detection. According to biochemical measurements and histopathological evaluation, ELB could alleviate the symptoms of alcoholic liver injury combined with gouty arthritis. In addition, chronic alcohol consumption and MSU activated inflammatory-related signaling such as TLR4/MyD88/NF-κB, NLRP3, and JAK2/STAT3 pathways in the liver and synovial tissues, while ELB significantly inhibited the activation of the inflammatory signaling pathway. In conclusion, ELB is protective in rats with chronic alcoholic liver injury and gouty arthritis, possibly mediated by the inhibition of TLR4/MyD88/NF-κB, NLRP3, and JAK2-STAT3 signaling pathways in both the hepatic and synovial tissues.

Recent studies have shown that Nogo-A and the Nogo-A receptor affect β-amyloid metabolism and the downstream Rho GTP enzyme signaling pathway, which may affect the levels of β-amyloid and tau. Nogo-A may play a key role in the pathogenesis of Alzheimer's disease. However, the underlying molecular mechanisms of Fasudil treatment in Alzheimer's disease are not yet clear. Our results have found that Fasudil treatment for two months substantially ameliorated behavioral deficits, diminished β-amyloid plaque and tau protein pathology, and alleviated neuronal apoptosis in APP/PS1 transgenic mice. More importantly, two well-established markers for synaptic function, growth-associated protein 43 and synaptophysin, were upregulated after Fasudil treatment. Finally, the levels of Nogo-A, Nogo-A receptor complex NgR/p75NTR/LINGO-1 and the downstream Rho/Rho kinase signaling pathway were significantly reduced. These findings suggest that Fasudil exerts its neuroprotective function in Alzheimer's disease by inhibiting the Nogo-A/NgR1/RhoA signaling pathway.

Gut microbiota is a large number of microorganisms that colonized in human intestinal tract. The “gut lung” axis is a two-way axis connecting the intestine and the lung. Gut microbiota and “gut lung” axis are involved in the occurrence and development of sepsis. When sepsis occurs, the gut mucosal barrier is damaged, the gut microbiota is imbalance, and bacterial translocation occurs. The lung is the first organ to be effected, and the pulmonary infection may lead to intestinal dysfunction.

Lagotis brachystachya Maxim is a characteristic herb commonly used in Tibetan medicine. Tibetan medicine records it as an important medicine for the clinical treatment of “Yellow Water Disease,” the symptoms of which are similar to that of arthritis. Our previous study showed that the flavonoid fraction extracted from L. brachystachya could attenuate hyperuricemia. However, the effects of the active flavonoids on gouty arthritis remain elusive, and the underlying mechanism is not understood. In the present study, the effects of the active flavonoids were evaluated in rats or Raw264.7 cells with gouty arthritis induced by monosodium urate (MSU) crystal, followed by the detection of TLR4, MyD88, pNF-κB, and NLR family pyrin domain-containing 3 (NLRP3) expression. The swelling of the ankle joint induced by MSU crystal began to be relieved 6 h post the administration with the active flavonoids. In addition, the active flavonoids not only alleviated MSU crystal-induced inflammation in synovial tissues by histopathological examination but also reduced tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the joint tissue fluid of MSU crystal-induced rats. Furthermore, Western blot analysis indicated that the active flavonoids reduced the production of these cytokines by inhibiting the TLR4/MyD88/NF-κB pathway and decreasing NLRP3 expression in synovial tissues of rats. More importantly, the inhibition of TLR4/MyD88/NF-κB pathway and NLRP3 expression was also confirmed in MSU-induced Raw264.7 cells. In conclusion, these results indicated that the active flavonoids from L. brachystachya could effectively attenuate gouty arthritis induced by MSU crystal through the TLR4/MyD88/NF-κB pathway and NLRP3 expression in vivo and in vitro, suggesting several potential candidates for the treatment of gouty arthritis.

Background: The COVID-19 pandemic has been an emergency worldwide. Web-based physical education is a choice for college students to keep on their study. The aim of this study was to compare the data of physical fitness of college students before and after web-based physical education.Methods: All the students of 2018 and 2019 in Wuhan University of Technology who had taken the web-based physical education class in 2020 were included in this study. The records of annual physical fitness tests of all the subjects in 2019 and 2020 which were carried out in September were reviewed, including weight, height, body mass index (BMI), vital capacity (VC), 50-m dash, sit-and-reach, standing long jump, male-specific pull-ups and 1,000-m race, and female-specific sit-ups and 800-m race.Results: There were 24,112 male and 9,690 female records of physical fitness tests included in our study. The results of 11,219 male and 4,651 female students who completed both physical fitness tests in 2019 and 2020 were employed for Wilcoxon signed-rank test. Declined performance was observed on male 50-m dash by 0.1 s, male 1,000-m race by 14 s, and female 800-m race by 11 s. Notably, the percentage of male obesity, based on BMI, rose from 10.6 to 15.2% and 17.1 to 21.8% for male overweight; correspondingly, the percentage of male normal weight declined from 55.9 to 51.9% and 16.4 to 11.1% for male thinness. The trend of increasing BMI in males should be paid attention to. Improved results on vital capacity, sit-and-reach, standing long jump for both males and females, female 50-m dash, female sit-ups, and male pull-ups were observed in 2020. All the results of physical fitness tests were significantly different between 2019 and 2020 (p < 0.01) by Wilcoxon signed-rank test.Conclusions: The changes of physical fitness tests before and after web-based physical education suggested that the focus should be placed on improvement for running tests through appropriate alternatives, such as fast running in place and shuttle run. In addition, the simple, convenient, and practical sport that require available equipment and little field should be considered for web-based physical education.

We have previously shown that biochanin A exhibits neuroprotective properties in the context of cerebral ischemia/reperfusion (I/R) injury. The mechanistic basis for such properties, however, remains poorly understood. This study was therefore designed to explore the manner whereby biochanin A controls endoplasmic reticulum (ER) stress, apoptosis, and inflammation within fetal rat primary cortical neurons in response to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, and in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R) injury. For the OGD/R in vitro model system, cells were evaluated after a 2 h OGD following a 24 h reoxygenation period, whereas in vivo neurological deficits were evaluated following 2 h of ischemia and 24 h of reperfusion. The expression of proteins associated with apoptosis, ER stress (ERS), and p38 MAPK phosphorylation was evaluated in these samples. Rats treated with biochanin A exhibited reduced neurological deficits relative to control rats following MCAO/R injury. Additionally, GRP78 and CHOP levels rose following I/R modeling both in vitro and in vivo, whereas biochanin A treatment was associated with reductions in CHOP levels but further increases in GRP78 levels. In addition, OGD/R or MCAO/R were associated with markedly enhanced p38 MAPK phosphorylation that was alleviated by biochanin A treatment. Similarly, OGD/R or MCAO/R injury resulted in increases in caspase-3, caspase-12, and Bax levels as well as decreases in Bcl-2 levels, whereas biochanin A treatment was sufficient to reverse these phenotypes. Together, these findings thus demonstrate that biochanin A can alleviate cerebral I/R-induced damage at least in part via suppressing apoptosis, ER stress, and p38 MAPK signaling, thereby serving as a potent neuroprotective agent.

Abstract Background Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied. Methods We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined. Results Mdivi-1 effectively suppressed EAE severity by reducing demyelination and cellular infiltration in the CNS. Mdivi-1 treatment decreased the phosphorylation of Drp1 (ser616) on CD4+ T cells, reduced the numbers of Th1 and Th17 cells, and increased Foxp3+ regulatory T cells in the CNS. Moreover, Mdivi-1 treatment effectively inhibited IFN-γ+, IL-17+, and GM-CSF+ CD4+ T cells, while it induced CD4+ Foxp3+ regulatory T cells in splenocytes by flow cytometry. Conclusions Together, our results demonstrate that Mdivi-1 has therapeutic potential in EAE by modulating the balance between Th1/Th17 and regulatory T cells.

Gynostemma pentaphyllum is a herbal medicine widely used in Asian countries, and its saponin extracts have been shown to possess potent anti-inflammatory effects. Gypenoside XVII, an active ingredient isolated from Gynostemma pentaphyllum, has been found to alleviate the inflammation induced by LPS in the BV2 microglia, according to our preliminary study. This study aims to evaluate whether Gypenoside XVII could attenuate depression-like symptoms in vivo and tries to demonstrate the involvement of the complement regulation in its antidepressant-like effect. The results showed that Gypenoside XVII significantly attenuated depression-like behaviors in the forced swimming test, tail suspension test and sucrose preference test. It also alleviated the acute stress-induced hyperactivity of serum corticosterone levels. Additionally, Gypenoside XVII significantly inhibited the activation of microglia and the expression of C3 in mice exposed to chronic unpredictable mild stress (CUMS). Meanwhile, the activation of C3aR/STAT3 signaling and the expression of proinflammatory cytokines was reversed by Gypenoside XVII. Moreover, CUMS induced excessive synaptic pruning by activating microglia, while Gypenoside XVII restored it in the prefrontal cortex. Our data demonstrated that Gypenoside XVII, the active ingredient of Gynostemma pentaphyllum, produced the antidepressant-like effects in mice, which was mediated by the inhibition of complement C3/C3aR/STAT3/cytokine signaling in the prefrontal cortex.

We wished to investigate the role of a tilapia skin collagen polypeptide (TSCP; molecular weight

Abstract A Gram‐staining positive facultative anaerobic, non‐motile strain, sk1b4T, was isolated from canker of symptomatic bark tissue of a Populus × euramericana. 16S rRNA gene sequence analyses showed that strain sk1b4T shared the highest similarity with Arcanobacterium phocisimile (94.1%). Within the phylogenetic tree, the novel isolate formed a distinct branch from Actinobaculum, Arcanobacterium, and Trueperella. The percentage of conserved proteins calculated from genomic sequence indicated a low level of relatedness between the novel strain and its phylogenetic neighbors. Growth of the novel strain occurred at temperatures between 10 and 41°C, and within a pH range of 6.0–9.0; optimal growth occurred at 30°C and at pH 6.0–9.0. Growth also occurred within a NaCl concentration of 1%–5% (w/v). The major fatty acids of the strain were C14:0, C16:0, and C18:1 ω9c, and major polar lipids were glycolipid, phosphatidylinositol mannoside, phospholipid, diphosphatidylglycerol, and phosphatidylglycerol. Respiratory quinone was absent. On the basis of phenotypic and genotypic characteristics, we propose that the novel isolate should be classified as a novel species in a new genus: Ancrocorticia populi gen. nov., sp. nov. The type strain is sk1b4T (=CFCC 14564T= KCTC 39919T).

The herbal pair of Coptidis Rhizoma (CR) and Euodiae Fructus (EF) is a classical traditional Chinese medicine formula used for treating gastro-intestinal disorders. In this study, we established a systematic method for chemical profiling and quantification analysis of the major constituents in the CR-EF herbal pair. A method of ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) for qualitative analysis was developed. Sixty-five compounds, including alkaloids, phenolics, and limonoids, were identified or tentatively assigned by comparison with reference standards or literature data. The UHPLC fingerprints of 19 batches of the CR-EF herbal pair samples were obtained and the reference fingerprint chromatograms were established. Furthermore, nine compounds among 24 common peaks of fingerprints were considered as marker components, which either had high contents or significant bioactivities, were applied to quality control of the CR-EF herbal pair by quantitative analysis. This UHPLC-DAD analysis method was validated by precision, linearity, repeatability, stability, recovery, and so on. The method was simple and sensitive, and thus reliable for quantitative and chemical fingerprint analysis for the quality evaluation and control of the CR-EF herbal pair and related traditional Chinese medicines.

Cadmium (Cd) is a developmental toxicant that induces fetal growth restriction (FGR). Placental endoplasmic reticulum (ER) stress is associated with FGR. This study investigated the effects of N-acetylcysteine (NAC) on Cd-induced placental ER stress and FGR. Pregnant mice were intraperitoneally injected with CdCl2 daily from gestational day (GD)13 to GD17. As expected, Cd reduced fetal weight and crown-rump length. Cd decreased the internal space of blood vessels in the placental labyrinth layer and inhibited placental cell proliferation. Several genes of growth factors, such as Vegf-a, placental growth factor, Igf1 and Igf1r, and several genes of nutrient transport pumps, such as Glut1, Fatp1 and Snat2, were down-regulated in placenta of Cd-treated mice. Moreover, Cd evoked placental ER stress. Of interest, NAC alleviated Cd-induced FGR. Additional experiment showed that NAC inhibited Cd-induced impairment of placental development and placental ER stress. Therefore, NAC may be exploited for prevention of Cd-induced placental insufficiency and FGR.

Peripheral nerve injury has been shown to result in ectopic spontaneous discharges on soma and injured sites of sensory neurons, thereby inducing neuropathic pain. With the increase of membrane proteins on soma and injured site neurons, the negatively charged sialic acids bind to the external domains of membrane proteins, resulting in an increase of this charge. We therefore speculate that the electrophoretic velocity of injured neurons may be faster than non-injured neurons. The present study established rat models of neuropathic pain via chronic constriction injury. Results of the cell electrophoresis test revealed that the electrophoretic velocity of injured neuronal cells was faster than that of non-injured (control) cells. We then treated cells with divalent cations of Ca 2+ and organic compounds with positive charges, polylysine to counteract the negatively charged sialic acids, or neuraminidase to specifically remove sialic acids from the membrane surface of injured neurons. All three treatments significantly reduced the electrophoretic velocity of injured neuronal cells. These findings suggest that enhanced sialic acids on injured neurons may accelerate the electrophoretic velocity of injured neurons.

Chitosan oligosaccharide (COS), a natural polysaccharide with good antioxidant and anti-inflammatory properties, is the depolymerized product of chitosan possessing various biological activities. The present study was designed to investigate the possible anti-aging effect of COS on the aging model mouse induced by d-galactose (d-gal) and explore the underlying mechanism. In the experiment, 48 male Kunming mice (KM mice) were randomly divided into the normal group, model group, positive group, and low-medium-high dose polysaccharide groups (300, 600, 1200 mg/kg/day). The results showed that COS, by intragastric gavage after subcutaneous injection of d-gal (250 mg/kg/day) into the neck of mice consecutively for eight weeks, gradually recovered the body weight, the activity of daily living, and organ indices of mice, as well as effectively ameliorated the histological deterioration of the liver and kidney in mice triggered by d-gal. To be specific, COS obviously improved the activities of antioxidant enzymes in liver and kidney of KM mice, including catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), as well as decreased malondialdehyde (MDA) levels when compared with those in model group mice. Furthermore, COS not only elevated the diminished levels of serum immunoglobulin G (IgG) and IgM induced by d-gal, but also significantly inhibited the d-gal-caused upregulation of serum alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid (UA) and creatinine (CREA) levels as compared with those of mice in the model group. These results demonstrate that COS has an obvious anti-aging activity in d-gal-induced subacute aging mice, the mechanism of which, to some extent, is associated with enhancing the antioxidant defenses, reducing oxidative stress, and improving the immune function of aging model mice.