Research progress of cGAS-STING signaling pathway in intestinal diseases.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signal has drawn much consideration due to its sensitivity to DNA in innate immune mechanisms. Activation of the cGAS-STIN signaling pathway induces the production of interferon and inflammatory cytokines, resulting in immune responses, or inflammatory diseases. The intestinal tract is a vital organ for the body's nutrition absorption, recent studies have had various points of view on the job of cGAS-STING pathway in various intestinal sicknesses. Therefore, understanding its role and mechanism in the intestinal environment can help to develop new strategies for the treatment of intestinal diseases. This article examines the mechanism of the cGAS-STING pathway and its function in inflammatory bowel disease, intestinal cancer, and long-injury ischemia-reperfusion, lists the current medications that target it for the treatment of intestinal diseases, and discusses the impact of intestinal flora on this signaling pathway, to offer a theoretical and scientific foundation for upcoming targeted therapies for intestinal disorders via the cGAS-STING pathway.

LncRNA XIST modulates miR-328-3p ectopic expression in lung injury induced by tobacco-specific lung carcinogen NNK both in vitro and in vivo.

BACKGROUND AND PURPOSE: It is well acknowledged that tobacco-derived lung carcinogens can induce lung injury and even lung cancer through a complex mechanism. MicroRNAs (MiRNAs) are differentially expressed in tobacco-derived carcinogen nicotine-derived nitrosamine ketone (NNK)-treated A/J mice. EXPERIMENTAL APPROACH: RNA sequencing was used to detect the level of long non-coding RNAs (lncRNAs). Murine and human lung normal and cancer cells were used to evaluate the function of lncRNA XIST and miR-328-3p in vitro, and NNK-treated A/J mice were used to test their function in vivo. In vivo levels of miR-328-3p and lncRNA XIST were analysed, using in situ hybridization. miR-328-3p agomir and lncRNA XIST-specific siRNA were used to manipulate in vivo levels of miR-328-3p and lncRNA XIST in A/J mice. KEY RESULTS: LncRNA XIST was up-regulated in NNK-induced lung injury and dominated the NNK-induced ectopic miRNA expression in NNK-induced lung injury both in vitro and in vivo. Either lncRNA XIST silencing or miR-328-3p overexpression exerted opposing effects in lung normal and cancer cells regarding cell migration. LncRNA XIST down-regulated miR-328-3p levels as a miRNA sponge, and miR-328-3p targeted the 3'-UTR of FZD7 mRNA, which is ectopically overexpressed in lung cancer patients. Both in vivo lncRNA XIST silencing and miR-328 overexpression could rescue NNK-induced lung injury and aberrant overexpression of the lung cancer biomarker CK19 in NNK-treated A/J mice. CONCLUSIONS AND IMPLICATIONS: Our results highlight the promotive effect of lncRNA XIST in NNK-induced lung injury and elucidate its post-transcriptional mechanisms, indicating that targeting lncRNA XIST/miR-328-3p could be a potential therapeutic strategy to prevent tobacco carcinogen-induced lung injury in vivo.

Efficacy and safety of hyperbaric oxygen therapy in acute ischaemic stroke: a systematic review and meta-analysis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of adjunctive hyperbaric oxygen therapy (HBOT) in acute ischaemic stroke (AIS) based on existing evidence. METHODS: We conducted a comprehensive search through April 15, 2023, of seven major databases for randomized controlled trials (RCTs) comparing adjunctive hyperbaric HBOT with non-HBOT (no HBOT or sham HBOT) treatments for AIS. Data extraction and assessment were independently performed by two researchers. The quality of included studies was evaluated using the tool provided by the Cochrane Collaboration. Meta-analysis was conducted using Rev Man 5.3. RESULTS: A total of 8 studies involving 493 patients were included. The meta-analysis showed no statistically significant differences between HBOT and the control group in terms of NIHSS score (MD = -1.41, 95%CI = -7.41 to 4.58), Barthel index (MD = 8.85, 95%CI = -5.84 to 23.54), TNF-α (MD = -5.78, 95%CI = -19.93 to 8.36), sICAM (MD = -308.47, 95%CI = -844.13 to 13227.19), sVCAM (MD = -122.84, 95%CI = -728.26 to 482.58), sE-selectin (MD = 0.11, 95%CI = -21.86 to 22.08), CRP (MD = -5.76, 95%CI = -15.02 to 3.51), adverse event incidence within ≤ 6 months of follow-up (OR = 0.98, 95%CI = 0.25 to 3.79). However, HBOT showed significant improvement in modified Rankin score (MD = 0.10, 95%CI = 0.03 to 0.17), and adverse event incidence at the end of treatment (OR = 0.42, 95%CI = 0.19 to 0.94) compared to the control group. CONCLUSION: While our findings do not support the routine use of HBOT for improving clinical outcomes in AIS, further research is needed to explore its potential efficacy within specific therapeutic windows and for different cerebral occlusion scenarios. Therefore, the possibility of HBOT offering clinical benefits for AIS cannot be entirely ruled out.

Transcriptome analysis of axillary buds in low phosphorus stress and functional analysis of TaWRKY74s in wheat.

BACKGROUND: Wheat is one of the main grain crops in the world, and the tiller number is a key factor affecting the yield of wheat. Phosphorus is an essential element for tiller development in wheat. However, due to decreasing phosphorus content in soil, there has been increasing use of phosphorus fertilizer, while imposing risk of soil and water pollution. Hence, it is important to identify low phosphorus tolerance genes and utilize them for stress resistance breeding in wheat. RESULTS: We subjected the wheat variety Kenong 199 (KN199) to low phosphorus stress and observed a reduced tiller number. Using transcriptome analysis, we identified 1651 upregulated genes and 827 downregulated of genes after low phosphorus stress. The differentially expressed genes were found to be enriched in the enzyme activity regulation related to phosphorus, hormone signal transduction, and ion transmembrane transport. Furthermore, the transcription factor analysis revealed that TaWRKY74s were important for low phosphorus tolerance. TaWRKY74s have three alleles: TaWRKY74-A, TaWRKY74-B, and TaWRKY74-D, and they all belong to the WRKY family with conserved WRKYGQK motifs. These proteins were found to be located in the nucleus, and they were expressed in axillary meristem, shoot apical meristem(SAM), young leaves, leaf primordium, and spikelet primordium. The evolutionary tree showed that TaWRKY74s were closely related to OsWRKY74s in rice. Moreover, TaWRKY74s-RNAi transgenic plants displayed significantly fewer tillers compared to wild-type plants under normal conditions. Additionally, the tiller numebr of the RNAi transgenic plants was also significantly lower than that of the wild-type plants under low-phosphorus stress, and increased the decrease amplitude. This suggestd that TaWRKY74s are related to phosphorus response and can affect the tiller number of wheat. CONCLUSIONS: The results of this research showed that TaWRKY74s were key genes in wheat response to low phosphorus stress, which might regulate wheat tiller number through abscisic acid (ABA) and auxin signal transduction pathways. This research lays the foundation for further investigating the mechanism of TaWRKY74s in the low phosphorus environments and is significant for wheat stress resistance breeding.

Systematic review and meta-analysis of the efficacy and safety of electroacupuncture for poststroke dysphagia.

Introduction: Optimal treatment strategies for post-stroke dysphagia (PSD) remain to be explored. Electroacupuncture (EA) has attracted widespread attention due to its simplicity, cheapness, and safety. However, the efficacy of EA in the treatment of PSD lacks high-level evidence-based medical support. This study aimed to systematically evaluate the clinical value of EA in the treatment of PSD. Methods: A total of seven databases were searched for relevant literature. All randomized controlled trials (RCTs) on EA alone or EA combined with other interventions for the treatment of PSD were assessed using the modified Jadad scale. The studies with a score of ≥4 were included. The quality of the included studies was then assessed using the Cochrane Collaboration's tool. The meta-analysis was performed using Rev. Man 5.3 software. Results: Twelve studies involving 1,358 patients were included in the meta-analysis. Meta-analysis results showed that the EA group was superior to the control group in terms of clinical response rate (OR = 2.63, 95% CI = 1.97 to 3.53) and videofluoroscopic swallowing study (VFSS) score (MD = 0.73, 95% CI = 0.29 to 1.16). There was no significant difference between the two groups in the standardized swallowing assessment (SSA) score (MD = -3.11, 95% CI = -6.45 to 0.23), Rosenbek penetration-aspiration scale (PAS) score (MD = -0.68, 95% CI = -2.78 to 1.41), Swallowing Quality of Life (SWAL-QOL) score (MD = 13.24, 95% CI = -7.74 to 34.21), or incidence of adverse events (OR = 1.58, 95% CI = 0.73 to 3.38). Conclusion: This study shows that EA combined with conventional treatment or other interventions can significantly improve the clinical response rate and VFSS score in patients with PSD without increasing adverse reactions.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=396840.

Electroacupuncture at HT5 + GB20 promotes brain remodeling and significantly improves swallowing function in patients with stroke.

Background: This study compared the differences in the degree of brain activation, and swallowing function scales in patients with post-stroke dysphagia after treatment. We explored the mechanism of cortical remodeling and the improvement effect of electroacupuncture on swallowing function in patients and provided a theoretical basis for the clinical application of electroacupuncture. Methods: Fifty patients with post-stroke dysphagia were randomized to the control or electroacupuncture group. The control group underwent conventional swallowing rehabilitation for 30 min each time for 12 sessions. In the electroacupuncture group, electroacupuncture was performed based on conventional swallowing rehabilitation for 30 min each time for 12 sessions. Cortical activation tests and swallowing function assessments were performed before and after treatment. Statistical analyses were used to investigate the differences within and between the two groups to explore the treatment effects. Results: There were no statistical differences in clinical characteristics and baseline data between the two groups before treatment. Cortical activation and swallowing function were improved to different degrees in both groups after treatment compared with before treatment. After treatment, the electroacupuncture group showed higher LPM (t = 4.0780, p < 0.001) and RPM (t = 4.4026, p < 0.0001) cortical activation and tighter functional connectivity between RS1 and LM1 (t = 2.5336, p < 0.05), RM1 and LPM (t = 3.5339, p < 0.001), RPM and LM1 (t = 2.5302, p < 0.05), and LM1 and LPM (t = 2.9254, p < 0.01) compared with the control group. Correspondingly, the improvement in swallowing function was stronger in the electroacupuncture group than in the control group (p < 0.05). Conclusion: This study demonstrated that electroacupuncture based on conventional treatment activated more of the cerebral cortex associated with swallowing and promoted functional connectivity and remodeling of the brain. Accompanying the brain remodeling, patients in the electroacupuncture group also showed greater improvement in swallowing function. Clinical trial registration: ClinicalTrials.gov, ChiCTR2300067457.

Angelica acutiloba Kitagawa flower induces A549 cell pyroptosis via the NF-κB/NLRP3 pathway for anti-lung cancer effects.

Angelica acutiloba Kitagawa, a traditional medicinal herb of the Umbelliferae family, has been demonstrated to have anticancer activity. In this study, we investigated the anti-lung cancer effects of two compounds extracted from A. acutiloba flowers: kaempferol-3-O-α-L-(4″-E-p-coumaroyl)-rhamnoside (KAE) and platanoside (PLA). MTT, cell colony formation, and cell migration (scratch) assays revealed that both KAE (100 µM) and PLA (50 µM and 100 µM) inhibited the viability, proliferation, and migration of A549 cells. Dichlorodihydrofluorescein diacetate assays showed that KAE and PLA also induced the generation of reactive oxygen species in A549 cells. Morphologically, A549 cells swelled and grew larger under treatment with KAE and PLA, with the most significant changes at 100 µM PLA. Fluorescence staining and measurement of lactate dehydrogenase release showed that the cells underwent pyroptosis with concomitant upregulation of interleukin (IL)-1ß and IL-18. Furthermore, both KAE and PLA induced upregulation of NF-κB, PARP, NLRP3, ASC, cleaved-caspase-1, and GSDMD expression in A549 cells. Subsequent investigations unveiled that these compounds interact with NLRP3, augment NLRP3's binding affinity with ASC, and stimulate the assembly of the inflammasome, thereby inducing pyroptosis. In conclusion, KAE and PLA, two active components of A. acutiloba flower extract, had significant anti-lung cancer activities exerted through regulation of proteins related to the NLRP3 inflammasome pathway.

Electroacupuncture at HT5 + GB20 produces stronger activation effect on swallowing cortex and muscle than single points.

Introduction: This study aimed to investigate the effects of electroacupuncture on cortical activation and swallowing muscle groups. The study examined brain activation in healthy subjects performing swallowing tasks during electroacupuncture. Additionally, the study analyzed electromyographic signals of swallowing muscle groups after electroacupuncture. Methods: Twenty-seven healthy subjects were randomly separated into three groups. They underwent electroacupuncture at HT5 acupoint (HT5 group), or GB20 acupoint (GB20 group), or HT5 + GB20 acupoint (HT5 + GB20 group) for 30 min of intervention. Subjects performed a swallowing task while receiving electroacupuncture. Functional near-infrared spectroscopy (fNIRS) was used to detect cortical activation and functional connectivity (FC). The mean amplitude values of the swallowing muscle groups after electroacupuncture were also measured. Statistical analysis was used to investigate the differences between the three groups. The protocol was registered with the China Clinical Trials Registry with the registration number ChiCTR2300067457. Results: Compared with the HT5 group, the HT5 + GB20 group showed higher cortical activation in the LM1 (t = 2.842, P < 0.05) and a tighter FC in the RM1 and LM1 (t = 2.4629, P < 0.05) with considerably increased mean amplitude values of the swallowing muscle groups (t = 5.2474, P < 0.0001). Increased FC was found in the HT5 + GB20 group compared to the GB20 group between the RM1 and RS1 (t = 2.9997, P < 0.01), RM1 and RPM (t = 2.2116, P < 0.05), RM1 and LM1 (t = 3.2078, P < 0.01), RPM and LM1 (t = 2.7440, P < 0.05). However, there were no statistically significant differences in cortical activation or mean amplitude values of swallowing muscle groups. Conclusion: This study showed that electroacupuncture at HT5 + GB20 acupoints particularly engaged the cerebral cortex related to swallowing, resulting in tighter functional connectivity and higher amplitude values of swallowing muscle groups than electroacupuncture at single acupoints. The results may reveal the mechanism of electroacupuncture for post-stroke swallowing dysphagia.

Role of mitochondrial stress and the NLRP3 inflammasome in lung diseases.

BACKGROUND: As an organelle essential for intracellular energy supply, mitochondria are involved in intracellular metabolism and inflammation, and cell death. The interaction of mitochondria with the NLRP3 inflammasome in the development of lung diseases has been extensively studied. However, the exact mechanism by which mitochondria mediate the activation of the NLRP3 inflammasome and trigger lung disease is still unclear. METHODS: The literatures related to mitochondrial stress, NLRP3 inflammasome and lung diseases were searched in PubMed. RESULTS: This review aims to provide new insights into the recently discovered mitochondrial regulation of the NLRP3 inflammasome in lung diseases. It also describes the crucial roles of mitochondrial autophagy, long noncoding RNA, micro RNA, altered mitochondrial membrane potential, cell membrane receptors, and ion channels in mitochondrial stress and regulation of the NLRP3 inflammasome, in addition to the reduction of mitochondrial stress by nuclear factor erythroid 2-related factor 2 (Nrf2). The effective components of potential drugs for the treatment of lung diseases under this mechanism are also summarized. CONCLUSION: This review provides a resource for the discovery of new therapeutic mechanisms and suggests ideas for the development of new therapeutic drugs, thus promoting the rapid treatment of lung diseases.

Corrigendum: Systematic review and meta-analysis of the efficacy and safety of electroacupuncture for poststroke dysphagia.

[This corrects the article DOI: 10.3389/fneur.2023.1270624.].

Severe Acute Hepatitis Outbreaks Associated with a Novel Hepacivirus in Rhizomys pruinosus in Hainan, China.

Members of the genus Hepacivirus have a broad range of hosts, with at least 14 species identified. To date, a highly pathogenic hepacivirus causing severe disease in animals has not been found. Here, by using high-throughput sequencing, a new hepacivirus was identified as the dominant and highly pathogenic virus in severe acute hepatitis outbreaks in bamboo rats (Rhizomys pruinosus), with ≈80% mortality; this virus emerged in February 2020 in two bamboo rat farms in China. Hepaciviral genome copies in bamboo rat liver were significantly higher than in other organs. Genomic sequences of hepacivirus strains from 12 sick bamboo rats were found to share 85.3 to 100% nucleotide (nt) identity and 94.9 to 100% amino acid (aa) identity and to share 79.7 to 87.8% nt and 90.4 to 97.8% aa identities with previously reported bamboo rat hepaciviruses of Vietnam and China. Sequence analysis further revealed the simultaneous circulation of genetically divergent hepacivirus variants within the two outbreaks. Phylogenetic analysis showed that hepacivirus strains from the present and previous studies formed an independent clade comprised of at least two genotypes, clearly different from all other known species, suggesting a novel species within the genus Hepacivirus. This is the first report of a non-human-infecting hepacivirus causing potentially fatal infection of bamboo rats, and the associated hepatitis in the animals potentially can be used to develop a surrogate model for the study of hepatitis C virus infection in humans and for the development of therapeutic strategies. IMPORTANCE Members of the genus Hepacivirus have a broad host range, with at least 14 species identified, but none is highly pathogenic to its host except for hepatitis C virus, which causes severe liver diseases in humans. In this study, a new liver-tropic hepacivirus species was identified by high-throughput sequencing as the pathogen associated with two outbreaks of severely acute hepatitis in hoary bamboo rats (Rhizomys pruinosus) on two farms in Hainan Province, China; this is the first reported highly pathogenic animal hepacivirus to our knowledge. Further phylogenetic analysis suggested that the hepaciviruses derived from hoary bamboo rats in either the current or previous studies represent a novel species within the genus Hepacivirus. This finding is a breakthrough that has significantly updated our understanding about the pathogenicity of animal hepaciviruses, and the hepacivirus-associated hepatitis in bamboo rats may have a use as an animal infection model to understand HCV infection and develop therapeutic strategies.

Grounded Theory and Social Psychology Approach to Investigating the Formation of Construction Workers' Unsafe Behaviour.

There have been limited studies analyzing the causes of construction workers' unsafe behaviour from the social psychology perspective. Based on a Grounded Theory approach, this study first identified and defined seven coded categories related to workers' dangerous behaviour on construction sites. The original qualitative data were obtained from individual site interviews conducted with 35 construction professionals. These main categories were found connected to workers' status of safety awareness and sense of danger, which affected the type of unsafe behaviours, i.e., proactive, passive, or reactive behaviour. By further integrating social cognitive psychology theories into workers' behavioural decision-making process, the formation mechanism framework and diagram were developed to describe construction workers' unsafe behaviours based on the dynamic process of balancing the individual desires and perceived safety risks. This study advances the body of knowledge in construction safety behavioural management by performing in-depth theoretical analysis regarding workers' internal desires, activated by external scenarios and intervened by a personal safety cognition system, which could result in different motivations and various behavioural outcomes. It is argued that safety cognition serves as a mediated moderation system affecting behavioural performance. Practical suggestions on developing a proper safety management system incorporating safety education in guiding construction workers' site behaviours are presented.

Apigenin exerts chemopreventive effects on lung injury induced by SiO2 nanoparticles through the activation of Nrf2.

Apigenin (APG) is a flavonoid widely distributed in fruits, vegetables, and herbs, with comprehensive pharmacological effects. In this paper, we report that APG can elicit a protective effect, which is comparable to those induced by gymnoside II/n-BuOH extracts of Bletilla striata, on SiO2-induced lung injury in vitro and in vivo. In vitro experiments showed that APG (25 µM) could restore the SiO2-decreased A549 cell viability and lower the apoptotic rate and the production of intracellular reactive oxygen species (ROS) in A549 cells treated with nm SiO2. Western blot results showed that APG (25 µM) could increase the level of Nuclear factor E2-related factor 2 (Nrf2) and its downstream proteins. In vivo experiments showed that APG (20 mg/kg) could potently alleviate the SiO2-elicited lung injury by enhancing the Nrf2 expression and thereby suppressing Bax/Bcl-2 pathway. The present study suggests that APG can significantly alleviate the SiO2-induced lung injury both in vitro and in vivo through, at least partially, activating Nrf2 expression.

Pregnane glycosides from Adonis amurensis and their bioactivity.

Seven undescribed pregnane glycosides named amurensides A-G and two known aglycones were isolated from the whole herb of Adonis amurensis Regel & Radde. Their structures were established based on 1D and 2D NMR spectroscopic analyses, high-resolution mass spectrometry, and acid hydrolysis. The cytotoxicity of all compounds against three tumor cell lines (HepG2, Caco-2, and A549) were evaluated. Among them, amurensides A-C and E showed moderate inhibitory effects on the growth of HepG2 cells, with IC50 values ranging from 15.6 to 48.7 µM (sorafenib, 7.5 ± 1.9 µM). Amurensides A、D and F displayed inhibitory effects on the growth of A549 cells with IC50 values of 18.8 ± 1.2, 12.4 ± 0.6, and 30.4 ± 0.1 µM (cis-platinum, 6.1 ± 0.1 µM), respectively.

Nontuberculous mycobacterial pulmonary disease and associated risk factors in China: A prospective surveillance study.

BACKGROUND: We aimed to address the knowledge gap that exists regarding the epidemiological, demographic, and clinical characteristics of nontuberculous mycobacterial pulmonary diseases (NTM-PDs) among smear-positive patients with symptoms suggestive of pulmonary tuberculosis (PTB) in China. METHODS: Prospective and national surveillance of NTM-PD was performed from 17 hospitals within the China Nontuberculous Mycobacteria Surveillance Study (CNTMS). Patients were eligible for inclusion if they had positive smears during hospitalization. Sputum specimens were collected for molecular species identification. RESULTS: 6,766 patients with valid results were included, consisting of 6,236 (92.2%) with PTB, 458 (6.8%) with NTM-PD, and 72 (1.0%) with colonization. The proportion of NTM-PD in PTB patients exhibited significant geographic diversity, ranging from 3.2% in the northwest to 9.2% in the south. The most prevalent species was Mycobacterium intracellulare, followed by Mycobacterium abscessus complex. Females, elderly people, and patients with bronchiectasis or COPD are at high risk for developing NTM-PD, while patients with diabetes have a lower risk of NTM-PD when compared with non-diabetic patients. Regarding clinical symptoms, lower rates of persistent cough and weight loss were noted in NTM-PD patients than in PTB patients. CONCLUSIONS: Approximately one-fifteenth of PTB patients are afflicted with nontuberculous mycobacterial infections in China. The prevalence of NTM shows geographic diversity across the country, and it showed a gradual increase from north to south and from west to east. NTM-PD patients are prone to exhibit less severe clinical symptoms than PTB patients, highlighting the importance of raising awareness of NTM diseases to improve decision making on how to best screen, diagnose, and treat NTM in TB-endemic settings.

Performance verification of a new fibrinogen assay.

BACKGROUND: Plasma fibrinogen (FIB), also known as factor I, plays a key role in the coagulation process. FIB testing in a clinical laboratory is crucial for coagulation screening and thrombolytic therapy. Here, we assessed the performance of a new, Chinese-made coagulation analyzer in the detection of FIB by comparing its precision and clinical feasibility with that of an imported system. METHODS: Blood samples were collected and plasmas were separated. The precision, linearity, reference interval, carryover rate, clinically reportable range, and clinical applicability of the domestic coagulation analyzer for FIB assay were assessed and validated based on the documents or industry standards issued by the United States Clinical and Laboratory Standards Institute (CLSI). RESULTS: The within-batch precision CVs (coefficient of variation) for the low- and high-level specimens were 2.92% and 0.24%, respectively, while the total precision CVs were 3.05% and 1.81%, respectively; all of them met the experimental requirements. The linear range was validated to cover 1.0-6.5 g/L, and a good linear relationship was obtained within the measurement range (R2=0.9998). The reference interval was verified for adults and the carryover rate was also evaluated to be 0.68%. The clinically reportable range was 0.33-13.0 g/L. With a sample size of 180 cases, the methodological comparison showed a correlation coefficient (r) of 0.9886 between Mindray ExC810 and Sysmex CS5100. Furthermore, when the level of FIB was higher than 4.0 g/L or lower than 1.0 g/L, the 2 systems had an agreement rate of 100%. CONCLUSIONS: Mindray ExC810 has a good performance for FIB assay in terms of precision, linearity, reference interval, carryover rate, and clinically reportable range. Methodological study showed that Mindray ExC810 has good agreement with Sysmex CS5100 and meets the requirements of laboratory testing. Therefore, Mindray ExC810 is suitable for FIB assay in clinical laboratory.

n-BuOH extract of Bletilla striata exerts chemopreventive effects on lung against SiO2 nanoparticles through activation of Nrf2 pathway.

BACKGROUND: SiO2 nanoparticles (nm SiO2) are ubiquitous in daily life and are acknowledged to be detrimental to human health. Bletilla striata is a traditional medicine used for generations in China and its polysaccharide has the anti-pulmonary fibrosis effect. PURPOSE: To investigate the lung protective effect of the small molecules (n-BuOH extract) of B. striata and clarify the underlying mechanism. STUDY DESIGN AND METHODS: C57BL/6 mice were subjected to intratracheal instillation with nm SiO2 nanoparticle suspension (7 mg/kg) to construct the in vivo model of nm SiO2-induced lung injury. The chemical profile of the n-BuOH extract of B. striata was investigated by HPLC analysis using authentic samples isolated from B. striata. Gymnoside II with the most potent chemoprotective capacity in the n-BuOH extract was used to clarify the potential bio-active molecular basis of the n-BuOH extract using in vitro experiments. The cytotoxicity, apoptosis, oxidative stress, and the Nrf2 signaling pathway were examined in SiO2-induced A549 cells. ML385 was adopted to down-regulate the Nrf2 expression. RESULTS: The n-BuOH extract of B. striata (40 mg/kg) could alleviate the SiO2-induced lung injury by increasing Nrf2 expression and thereby suppressing Bax/Bcl-2 pathway in the nm SiO2-induced mice model. The chemical profile study showed that militarine, gymnoside II, and 4-allyl-2, 6-dimethoxyphenol glucoside were the main constituents of n-BuOH extract. Studies on gymnoside II revealed that it could partially restore the SiO2-induced decline in cell viability while did not affect the growth of normal A549 cells within the concentration range of 1-50 µM, suggesting a protective effect against nm SiO2 in lung A549 cells. The hoechst 33258 staining, flow cytometry, and western blot experiments demonstrated that gymnoside II (25 µM) could partially reverse the SiO2-induced cell apoptosis and ROS production by enhancing Nrf2, HO-1, and γ-GCSc expressions and Nrf2 silencing by ML385 abrogated the effects of gymnoside II (25 µM) on apoptosis and ROS production in A549 cells. CONCLUSION: The present study suggests that in addition to the polysaccharide, small molecules (n-BuOH extract) of B. striata can also elicit a protective effect on lung injuries through the Nrf2-dependent mechanism and gymnoside II is one of the main bio-active constituents contributing to the n-BuOH extract-elicited lung protective effect against nm SiO2.

Predicting factors of tumor progression in adult patients with low-grade glioma within five years after surgery.

BACKGROUND: Glioma is the most common primary intracranial tumor with the worst prognosis whose 5-year mortality rate is second only to pancreatic cancer and lung cancer among systemic tumors. WHO divides gliomas into grades I to IV, with grades I and II as low grades. Low-grade gliomas tend to occur in people between the ages of 30 and 40, who usually have the characteristics of well-differentiated, slow growth, and low invasiveness. Timely diagnosis and surgery are the main treatment strategies for low-grade gliomas. The current ideal treatment represents the MST reaching average seven years. However, many patients relapse with adverse outcomes. It's important to identify high-risk patients by predicting factors in adult patients with low-grade glioma. METHODS: A total of 287 patients who were treated in our hospital from February 2011 to May 2015 were included in the final analysis according to the inclusion and exclusion criteria. The patients were divided into progression-free groups and progression groups according to the results of 5-year follow-up after surgery by information like patients' baseline data, surgical data, postoperative follow-up data. The ROC was used to analyze the greatest quantitative treatment boundary value and distinguish high and low risk. Kaplan-Meier survival curve was used to analyze risk factors' predictive value for patients' postoperative results. RESULTS: The results of 5-year follow-up showed 122 cases (42.5%) had no progression (progression-free group), 165 cases (57.5%) had progression (progression group). Univariate and multivariate analysis showed that age older than 50 (OR =1.42, P=0.013), partial resection of tumor (OR =1.86, P=0.027), tumor diameter larger than 5 cm (OR =1.85, P=0.022) and long-term statins treatment before surgery (OR =0.36, P=0.036) were closely associated with tumor progression. The Kaplan-Meier survival curve showed patients aged older than 50, partial resection of the tumor, a tumor diameter larger than 5 cm whose results were poor, while long-term statins treatment before surgery had a better prognosis within the 5-year follow-up. CONCLUSIONS: Patients aged older than 50, partial resection of the tumor, tumor diameter larger than 5 cm and long-term statins treatment before surgery were closely related to the prognosis after surgery.

Treatment of coronavirus disease 2019 in Shandong, China: a cost and affordability analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is now a global public threat. Given the pandemic of COVID-19, the economic impact of COVID-19 is essential to add value to the policy-making process. We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China, and also assess the factors affecting their costs. METHODS: This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020. The total direct medical expenditures were analyzed by cost factors. We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income. Differences between groups were tested by student t test and Mann-Whitney test when appropriate. A multiple logistic regression model was built to determine the risk factors associated with high cost. RESULTS: A total of 70 COVID-19 patients were included in the analysis. The overall mean cost was USD 6827 per treated episode. The highest mean cost was observed in drug acquisition, accounting for 45.1% of the overall cost. Total mean cost was significantly higher in patients with pre-existing diseases compared to those without pre-existing diseases. Pre-existing diseases and the advanced disease severity were strongly associated with higher cost. Around USD 0.49 billion were expected for clinical manage of COVID-19 in China. Among rural households, the proportions of health insurance coverage should be increased to 70% for severe cases, and 80% for critically ill cases to avoid catastrophic health expenditure. CONCLUSIONS: Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance. The cost for drug acquisition is the major contributor to the medical cost, whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19. Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.

Triterpenoids from Liquidambar Fructus induced cell apoptosis via a PI3K-AKT related signal pathway in SMMC7721 cancer cells.

A previously undescribed taraxerene-type triterpenoid possessing a class of rare natural taraxerene triterpenoid possessing skeleton with 14, 28-lactone, two undescribed oleane-type triterpenoids, and twenty-five known triterpenoids were isolated from Liquidambar formosana (Hamamelidaceae). The structures of undescribed compounds were determined on the basis of 1D and 2D NMR spectroscopic, HR-ESI-MS, and X-ray crystallographic data analysis. Among the isolates, ursolic acid, 3,6-dion-20(29)-lupen-28-oic acid, and 3-oxo-12α-hydroxyoleanan-28,13ß-olide induced a significant apoptosis in SMMC7721 cells in the flow cytometer experiment with apoptosis rates of 94.5%, 57.3% and 89.9% at 8.0 µM, respectively, exhibiting near equivalent apoptosis-inducing abilities to that positive drug taxol (apoptotic rate of 71.2% at 1.4 µM). Mechanism studies suggested that these three compounds could regulate the mitochondrial pathway by up-regulating the expressions of pro-apoptotic factors (Bad and Bax) and activating caspase-3 and caspase-9 to induce apoptosis. Further studies indicated that the pro-apoptotic effects of these three compounds were associated with PI3K-AKT pathway inhibition. Taken together, these studies provide evidence that triterpenoids from L. Fructus are promising candidates for the hepatocellular carcinoma therapy.