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Monkeypox has spread unprecedentedly to nearly 100 countries and infected more than 51,000 people since 1 May 2022. This large-scale outbreak constituted a public health emergency of international concern (PHEIC), as declared by the World Health Organization. To better recognize and control this outbreak, we explore here through phylogenetic analysis the origins of MPXVs and their strains circulating in 2022, which remain unclear so far. Our results suggest that MPXVs possibly originated from some cowpox viruses and three lineages of MPXVs within Clade IIb circulated in 2022. Our results also suggest that two MPXVs respectively similar to the two MPXVs exported from Nigeria to the USA in 2021, ON676708/USA/2021 and ON676707/USA/2021, evolved into two lineages and sparked the large-scale outbreak in 2022, after their unknown evolutionary and epidemiological journeys possibly in Nigeria, the USA, or other countries before May 2022. This view does not stigmatize any country, because monkeypox is an endemic zoonosis in west Africa with wildlife reservoirs, and its large-scale outbreak in 2022 also resulted from the global decline of population immunity against smallpox due to the cease of vaccination against smallpox decades ago.

Recently, several clinical studies have evaluated the first-line use of immune checkpoint inhibitors (ICIs) combined with platinum-doublet chemotherapy in patients with non-squamous non-small cell lung cancer (NSCLC), however, the differences in safety and efficacy between the various types of ICIs still require investigation. In this study, we evaluated the efficacy and safety of the first-line use of ICIs combined with platinum-doublet chemotherapy in patients with non-squamous NSCLC by meta-analysis and indirect comparison.Literature searches were performed using PubMed, the Cochrane Library, Embase, China Knowledge Resource Integrated Database, and Wanfang Data to identify all relevant randomized clinical trials for non-squamous NSCLC after 2010. Overall survival (OS), progression-free survival (PFS), and adverse effects (AEs) were pooled for meta-analysis and indirect comparison. Subgroup analyses were conducted to examine the factors associated with PFS.The meta-analysis showed that the additional use of ICIs could significantly improve PFS and OS. The indirect comparison showed no significant difference in pembrolizumab + chemotherapy and atezolizumab + chemotherapy in the reducing of disease progression, while a significant difference in restricted mean survival time (RMST) was found between pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy. A significant increase in grade ≥3 AEs was observed with the additional use of atezolizumab combined with chemotherapy. Subgroups including PD-1 status [high (50%), intermediate (1-49%), and negative (1%) expression], sex (male and female), smoking status (current or former smoker, and never smoked), liver metastases (with and without), age (65 and ≤65) and Eastern Cooperative Oncology Group (ECOG) score (ECOG=0 and ECOG=1) were all associated with better PFS.This meta-analysis confirmed the treatment effects of ICIs combined with chemotherapy for non-squamous NSCLC. The pembrolizumab combination group had a greater RMST benefit compared with the atezolizumab combination group. Furthermore, our study also demonstrated a PFS advantage for non-squamous NSCLC using ICIs combined with chemotherapy irrespective of programmed death-ligand 1 (PD-L1) expression level, smoking status, liver metastasis status, sex, age and ECOG score. Due to the significant increase in AEs (grade 3), more attention should be paid to the additional use of atezolizumab.

Objectives Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20 ins) mutations are generally associated with de novo resistance to first- or second-generation EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the real efficacy of osimertinib for this subset remains elusive. We performed this study to investigate the real efficacy of osimertinib for Chinese advanced NSCLC patients harboring EGFR ex20 ins mutations. Materials and methods We retrospectively collected data of metastatic NSCLC patients with EGFR ex20 ins mutations who were treated with osimertinib 80 mg or 160 mg once daily in our center from June 2017 to May 2020. Progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed. Results A total of 62 cases with EGFR ex20 ins mutations were included, and the major insertion variant was D770_N771insSVD and V769_D770insASV (45.1 %). Concurrent TP53 mutation was most commonly observed (59.7 %). Four patients showed partial response, 29 cases with stable disease and 29 showed progressive disease as best response to osimertinib (ORR: 6.5 %, DCR: 53.2 %). The median PFS (mPFS) in total patients was 2.3 (95 %CI, 1.5–3.1) months. Patients harboring A763_Y764insFQEA/D770delinsGY variants showed numerically longer mPFS than those with other variants (4.2 vs. 2.2 months, P = 0.164). Patients who failed to osimertinib and occurred extracranial progression showed similar mPFS to those with intracranial progression (2.3 vs. 1.9 months, P = 0.142). Median PFS was not significantly different between patients who received osimertinib 80mg or 160mg once daily (2.5 vs. 1.3 months, P = 0.161), either with no significance when it used in fist-line setteing or bove (3.0 vs. 2.2 months, P = 0.639). Conclusion The unique insertion variant A763_Y764insFQEA and D770delinsGY might better respond to osimertinib than other ex20 ins subtypes. Osimertinib either 80 mg or 160 mg once daily showed less activity in Chinese NSCLC patients harboring diverse EGFR ex20 ins mutations.

Some nucleotide insertions or deletions (indels) in open reading frames of virus genes lead to frameshift mutations (FSMs), which can drastically change amino acid sequences. Most FSMs are deleterious and inhibited by natural selection, but some FSMs could aid viruses in adapting to new hosts, escaping immunity, or changing viral pathogenicity or transmissibility. Surprisingly, various fundamental aspects of FSMs in virus evolution remain unknown. In this report, we identified 679 FSMs in the genomes of viruses from 13 randomly selected animal virus families using randomly selected sequences. The 679 FSMs were formed with 1−5 indels, and most (89.4%) FSMs were fixed through the compensatory mechanism with two indels. Each FSM changed 3−209 (mean=15.4, median=13) amino acid residues. FSM frequencies were usually higher in viral sequences with lower sequence identities and steeply increased when sequence identities declined to 60.0%−69.9% or 70.0%−79.9%. This suggests that FSMs are more important to the macroevolution (i.e., inter-species evolution, including speciation) than to the microevolution (i.e., intra-species evolution) of viruses. This study provided novel evidence for the hopeful monster hypothesis in evolutionary biology. Furthermore, we found that FSMs occurred at different frequencies among genes in the same virus genomes and among virus families. Collectively, this study revealed multiple fundamental features of FSMs in virus evolution for the first time and provided novel insights into the mechanisms of macroevolution and speciation.

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to be at least equally effective to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% v 97%, and 95% v 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% v 87%, and 85% v 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.

To investigate the characteristics of gene mutation in elderly patients with acute myeloid leukemia (AML) and its effect on prognosis.The clinical and laboratorial characteristics of 54 AML patients (≥60 years old) in Department of Hematology, Tangdu Hospital were analyzed retrospectively during April 2016 to October 2019. Thirty-four AML/myelodysplastic syndrome/myeloproliferative neoplasm related mutant genes were detected by second-generation sequencing technology, and their clinical characteristics, treatment effect, and influence on prognosis were analyzed.All the patients received DAC+CAG induction treatment, after 1-2 couses of treatment, 36 cases (66.7%) achieved complete response, with a total effective rate of 75.9%, and the median survival time was 17 months. The most frequent mutant genes were TET2 (33.3%), CEBPA (31.5%), DNMT3A (18.5%), ASXL1 (16.7%), NRAS (14.8%), RUNX1 (14.8%), FLT3-ITD (12.9%), TP53 (12.9%), NPM1 (12.9%), and IDH2 (12.9%). Among 7 patients with TP53 mutation, 6 cases obtained complete response after 1-2 courses of induction treatment, but there was no statistically significant difference in the effect on prognosis. Patients with FLT3-ITD and NRAS mutations had shorter overall survival time compared with who had no mutation (P=0.47, P=0.48). Multivariate analysis showed that FLT3-ITD and NRAS mutations were poor prognostic factors.The incidence of TET2 gene mutation is high in elderly AML patients. AML patients with TET2 and TP53 mutations may benefit from Decitabine-based chemotherapy. However, patients with FLT3-ITD and NRAS mutations have a short survival time, and may have a poor prognosis.老年急性髓系白血病患者的基因突变特征及预后分析.探讨老年急性髓系白血病患者的基因突变特征及对预后的影响.回顾性分析2016年4月至2019年10月在空军军医大学唐都医院血液科接受治疗的54例年龄≥60岁初治急性髓系白血病患者的临床资料，采用二代测序技术检测34个急性髓系白血病/骨髓增生异常综合征/骨髓增殖性肿瘤相关突变基因，分析其临床特征、治疗效果及对预后的影响.54例患者均采用DAC+CAG方案诱导治疗，经过1-2个疗程治疗达完全缓解者36例（66.7%），总有效率75.9%，中位生存时间为17个月。突变频率较高的基因依次为TET2（33.3%）、CEBPA（31.5%）、DNMT3A （18.5%）、ASXL1（16.7%）、NRAS（14.8%）、RUNX1（14.8%）、FLT3-ITD（12.9%）、TP53（12.9%）、NPM1（12.9%）、 IDH2（12.9%）。7例伴TP53突变的患者中6例经1-2个疗程诱导治疗获得完全缓解，但对预后的影响无统计学差异。伴FLT3-ITD和NRAS基因突变患者的总生存时间均短于无突变的患者（P=0.47，P=0.48）。多因素分析显示，FLT3-ITD及NRAS基因突变是预后不良因素.老年急性髓系白血病患者TET2基因突变发生率高。伴TET2和TP53基因突变的老年急性髓系白血病患者可从地西他滨中获益，而伴FLT3-ITD、NRAS基因突变的患者生存时间短，可能预后不良.

Food safety and quality issues are becoming increasingly important and attract much attention, requiring the development of better analytical platforms. For example, high-resolution (especially Orbitrap) mass spectrometry simultaneously offers versatile functions such as targeted/non-targeted screening while providing qualitative and quantitative information on an almost unlimited number of analytes to facilitate routine analysis and even allows for official surveillance in the food field. This review covers the current state of Orbitrap mass spectrometry (OMS) usage in food analysis based on research reported in 2012-2019, particularly highlighting the technical aspects of OMS application and the achievement of OMS-based screening and quantitative analysis in the food field. The gained insights enhance our understanding of state-of-the-art high-resolution mass spectrometry and highlight the challenges and directions of future research.

Flavonoids, among the major bioactive ingredients in many traditional Chinese medicines, have been widely considered due to their pharmacological and biochemical effects: antioxidant, anti-vascular...

There are two contrary opinions regarding the risk if mainland China (MC) moves away from its zero-COVID policy. Some experts think the risk shall be much lower than influenza as per MC’s own COVID-19 case fatality rate (CFR), while some other experts think the risk shall be much higher than influenza as per the COVID-19 CFRs of other regions. We elucidate here that this and multiple other striking differences in the CFR between various scenarios all support and substantially resulted from the view that good IDM is highly powerful to mitigate COVID-19, where IDM (isolation-disinfection-maintenance) means isolation of COVID-19 cases from other people, disinfection of their living environments, and health maintenance (e.g., rest, nutrition, breathing). The high effect of good IDM is also supported by the theoretic functions of IDM in minimizing co-infections and maintaining body functions, and the fact that all the 505 COVID-19 deaths reported in MC in 2022 before May 5 died directly of severe underlying diseases with COVID-19. Although it is tough for people in poverty to obtain good IDM, good IDM can be feasible at home for the most mild cases and in hospitals for the most severe cases. Therefore, good IDM can be crucial to mitigating COVID-19 worldwide. It also suggests that the risk for China to end its zero-COVID policy depends on China’s control policies or measures. Based on the effect of IDM, the cautious co-existence policy was proposed for COVID-19 control. This policy could reduce the whole death toll in MC because good IDM is non-specific and can reduce deaths of various other diseases. The cautious co-existence policy (non-specific) and the vaccination policy (specific) aid each other to mitigate COVID-19, and they cannot replace each other. Those who are qualified in health for vaccination should be vaccinated against COVID-19 timely.

In recent years, the taxonomy of the families of Phenuiviridae, Nairoviridae, and Peribunyavidae in Bunyavirales was updated frequently, because many novel viruses in these families have been identified and the species demarcation criteria of these families have been changed. As per these criteria and sequence analysis, we found that the taxonomy of 19 species in these families should be revised. We presented six proposals for optimizing virus species taxonomy using the examples from these families. First, the species demarcation criteria for the same family (e.g., Peribunyavidae) should be unified. Second, the methods and parameters for the taxonomic calculation in the same order (e.g., Bunyavirales) should be unified. Third, virus species taxonomy should be based on phylogenetic relationships, rather than a cutoff value of sequence identities that is a self-contradictory demarcation criterion, although sequence identities aid virus taxonomy greatly. Fourth, virus species taxonomy should be based on the phylogenetic relationship of a key viral gene (e.g., the RdRp gene of Bunyavirales), which is important for the taxonomy of virus recombinants or reassortants. Fifth, a virus can be demarcated without a species before its biomedical significance has been revealed. Sixth, names of all viruses and virus species should be constituted exclusively with common characters (English letters and Arab numbers), to minimize difficulty in spelling and communication. These proposals are rational, flexible, and can accommodate all known viruses. They can also bridge the taxonomy history and the future demands due to their flexibility.

ObjectivesThis study aimed to determine the changing prevalence of clustering of cardiovascular disease (CVD) risk factors across socioeconomic spectra in rural southwest China.DesignData were collected from two waves of cross-sectional health interviews and examinations among individuals aged ≥35 years in rural China. Anthropometric measurements, blood pressure and fasting blood sugar levels were recorded for each participant.SettingThis study was conducted in rural Yunnan Province of China.Participants8187 individuals in 2011 and 7572 in 2021 consented to participate in this study.ResultsFrom 2011 to 2021, prevalence increased of hypertension (26.1% vs 41.6%), diabetes mellitus (5.9% vs 9.8%), obesity (5.9% vs 12.0%) and central obesity (50.0% vs 58.3%) (pConclusionThe prevalence of clustering of CVD risk factors increased substantially across all socioeconomic spectra in rural southwest China from 2011 to 2021. Future efforts to implement comprehensive lifestyle interventions to promote the prevention and control of CVD should in particular focus on men, those of Han ethnicity and those with low socioeconomic status.

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuivirid species, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and research on phenuiviruses has made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and important virus family and conduct relevant risk analysis.

To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML) patients with ASXL1 mutation.The clinical data of 229 newly diagnosed AML patients treated in our hospital from April 2016 to October 2019 were analyzed retrospectively. The next-generation sequencing technology was used to detect gene mutations in all the patients, the clinical characteristics of the patients with ASXL1 mutation were analyzed.ASXL1 gene mutation was detected out in 45 patients(19.6%). Among these patients, the frameshift mutation (n=22,48.9%) was most common, followed by missense mutation (n=15, 33.3%) and nonsense mutation (n=8,17.8%), respectively, all of them were located at exon 12. The median mutation rate was 32.47%(range, 2.74%-53.50%). The median age of the patients with ASXL1 mutation was 54(range, 14-74) years old, and most of the patients were male, and most of them with the history of MDS or MPN, and low white blood cell count at the initial diagnosed (P0.05). Patients with ASXL1 mutation showed a lower CR rate than that of without ASXL1 mutation. Patients with or without ASXL1 mutation showed a statistically significant difference in survival at 20 months (P=0.042), while there was no significant difference between the patients in the two groups over 20 months (P=0.505). All the 6 patients with ASXL1 mutation in low-risk group were survived, while the median OS time was 16 months in the high-risk group(P=0.034). Multivariate analysis showed that the history of MDS or MPN and CR rate from induction therapy were the independent risk factors affecting survival of the patients.Frameshift mutation is commonly in AML patients with ASXL1 gene mutation, and ASXL1 mutation were more often in men, the history of MDS or MPN, and low white blood cell count. The CR rate of the patients with ASXL1 mutation was lower than that of the AML patients without ASXL1 mutations, AML patients with ASXL1 mutation showed poor short-term efficacy, but there was no significant difference between the two groups in long-term survival over 20 months.伴ASXL1基因突变的急性髓系白血病患者的临床特征及预后分析.探讨伴有ASXL1基因突变的急性髓系白血病（AML）患者的临床特征及预后.回顾性分析2016年4月至2019年10月就诊于空军军医大学唐都医院血液科的初诊AML患者229例的临床资料，采用二代测序技术进行基因突变检测，分析ASXL1基因突变患者的临床特征并进行预后分析.共45例（19.6%）患者检测到ASXL1基因突变，移码突变22例（48.9%），错义突变15例（33.3%），无义突变8例（17.8%），均位于12号外显子。中位突变比例为32.47%（2.74%-53.50%）。伴有ASXL1基因突变的患者中位年龄为54（14-74）岁，以男性患者多见、且前期多有MDS或MPN病史、初诊时外周血白细胞数不高。伴有ASXL1突变组的患者诱导化疗完全缓解率低于无ASXL1突变的患者。伴或不伴ASXL1突变的患者在20个月内的生存具有统计学差异（P=0.042），而20个月以上的两组患者OS时间无差异（P=0.505）。伴ASXL1基因突变患者中，预后良好者6例全部存活，预后不良组中位OS时间16个月（P＝0.034）。多因素分析显示，前期血液病史及诱导治疗是否获得CR是影响预后的独立不良因素.伴ASXL1突变的AML患者中以移码突变常见。ASXL1突变多见于男性，起病白细胞不高，且易存在前期血液病史。伴ASXL1突变AML患者的CR率低于无ASXL1突变组，且短期疗效更差（≤20个月），但20个月以上的长期生存无显著差异.

Background: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been the major bottleneck that limits the long-term clinical efficacy. Therefore, the exploration of novel strategies for the treatment of non-small cell lung cancer (NSCLC) is urgent. Sijunzi Tang (SJZ) has been usually used as a complementary therapy for cancer patients that can prolong their overall life. Nevertheless, its underlying mechanism when combined with EGFR-TKIs is not clear. Methods: Here, the anti-tumor activity was evaluated by determining cell viability by using the Cell Counting Kit-8 (CCK-8). A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to simultaneously quantify nine metabolites in the glutamine metabolic pathway, such as glutamine, glutamate, αketoglutaric acid, fumarate, succinate, citrate, cis-aconitate, alanine, and malate in PC-9/GR cells. Results: The results showed that SJZ could enhance the sensitivity of lung cancer cells to gefitinib. The content of glutamine and glutamate in the SJZ/gefitinib group was significantly lower than that in the gefitinib group, while the concentration of other metabolites did not change significantly. Conclusion: In summary, SJZ can reverse gefitinib resistance by modulating glutamine metabolism. Our results suggested that SJZ might be a potential resistance reversal herbal medicine and combined with gefitinib might be a promising strategy for the therapy of lung cancer. Also, the research will provide novel insights for the study of the mechanisms on Traditional Chinese medicine (TCM) prescriptions-reversed resistance of EGFR-TKIs, and scientific basis for the combined treatment of lung cancer with TCM and EGFR-TKIs.

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuiviruses, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and researches on phenuiviruses have made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and very important virus family.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Lung cancer ranks as a leading cause of death. Although targeted therapies usually trigger profound initial patient responses, these effects are transient due to drug resistance and severe side effects. Xihuang Pill (XHW) is a popular Chinese medicine formula that might benefit cancer patients when used as a complementary therapy. However, its underlying mechanism when combined with anticancer drugs is not clearly understood. Here, we used an integrated strategy to reveal the regulatory properties of XHW in increasing the antitumor activity of anlotinib in lung cancer. We evaluated the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung carcinoma (LLC). We applied untargeted metabolomics to identify the differences metabolism and found that XHW improved the effects of anlotinib on lung cancer. The components and targets related to the effects of XHW treatment on lung cancer were obtained through network pharmacology. Then, by integrating the biologically active components of XHW and anlotinib as well as the treatment-responsive metabolites and their related targets, an interaction network was constructed to evaluate the combination therapy. Finally, important protein candidates for this response were verified by immunohistochemistry of tumor tissues. The results showed that XHW significantly improved the inhibitory effect of anlotinib on tumor growth in LLC-bearing mice. Additionally, 12 differentially-abundant metabolites were identified by untargeted metabolomics in the XHW/anlotinib group compared with the XHW or anlotinib groups, and they were mainly enriched in fatty acid metabolism, lipid metabolism and amino acid metabolism pathways. Anlotinib, 23 components in Shexiang, 2 components in Niuhuang, 30 components in Ruxiang and 60 components in Moyao work together to act on 30 targets to regulate hexadecanoic acid (also named palmitic acid), linoleic acid, lactosylceramide, adrenaline, arachidonic acid and lysoPC(18:1(9Z)). The results of immunohistochemistry showed that XHW combined with anlotinib reduced the expression of PDGFRA in tumors. Overall, the key metabolites of XHW that enhances the efficacy of anlotinib were regulated by a multicomponent and multitarget interaction network. Our results suggested that anlotinib combined with XHW may be a promising strategy for the treatment of lung cancer.

Exogenous toxicants (e.g. arsenic, cigarette smoke), trigger oxidative stress, and initiate the pathogenesis of many human diseases. Induction of nuclear factor E2-related factor 2 (Nrf2) counteracts exogenous toxicant-induced oxidative insults. Using a high-throughput screen, we firstly identified a citrus polymethoxyflavone, (2S)-5,6,7,3′,4′-pentamethoxyflavanone (PMF), to be an Nrf2 activator, and an investigation targeting Nrf2 pathway was performed. Our study indicated that: (i) PMF activated Nrf2 and its downstream genes, NQO1 and γ-GCS, and enhanced the stabilization of Nrf2 through inhibiting Nrf2 ubiquitination. (ii) Inhibition of PI3K, p38 MAPK, PKC and PERK by specific kinase inhibitors suppressed PMF-induced activation of Nrf2. (iii) PMF conferred Nrf2-dependent protection against sodium arsenite- and cigarette smoke extract- induced cytotoxicity in lung epithelial cells. Collectively, our data demonstrate that PMF is a novel Nrf2 activator with potential prevention against oxidative insults. The diverse pharmacological functions of citrus polymethoxyflavone might be related to their ability of activating Nrf2 pathway.

Background Oxidative stress contributes to the pathogenesis of many human diseases. Cinnamon is a worldwide used spice, dietary supplement and traditional medicine, and is used for the therapy of oxidative stress related diseases. A well-established concept is that the functions of cinnamon preventing oxidative stress-induced diseases are attributed to the occurrence of cinnamaldehyde and its analogues. Hypothesis In our continuous searching of natural molecules with antioxidant capacity, we have found that cinnamaldehyde and its analogues in cinnamon are weak inhibitors of oxidative stress, and thus we speculate that there are novel and/or potent molecules inhibiting oxidative stress in cinnamon. Study design and methods A systemic phytochemical investigation of cinnamon using column chromatography was performed to identify the chemical constituents of cinnamon, and then their capacity of inhibiting oxidative stress and action of mechanism targeting Nrf2 pathway were investigated using diverse bioassay, including NAD(P)H: quinone reductase (QR) assay, immunoblot analysis, luciferase reporter gene assay, immunofluorescence and flow cytometry. Results Cinnamon improved the intracellular antioxidant capacity. A systemic phytochemical investigation of cinnamon gave the isolation of twenty-two chemical ingredients. The purified constituents were tested for their potential inhibitory effects against oxidative stress. Besides cinnamaldehyde analogues, a lignan pinoresinol (PRO) and a flavonol (-)-(2R,3R)-5,7-dimethoxy-3′, 4′-methylenedioxy-flavan-3-ol (MFO) were firstly identified to be inhibitors of oxidative stress. Further study indicated that PRO and MFO activated Nrf2-mediated antioxidant response, and protected human lung epithelial cells against sodium arsenite [As(III)]-induced oxidative insults. Conclusion The lignan PRO and the flavonoid MFO are two novel Nrf2 activators protecting tissues against oxidative insults, and these two constituents support the application of cinnamon as an agent against oxidative stress related diseases.

Increasing evidence demonstrated that alternative splicing (AS) plays a vital role in tumorigenesis and clinical outcome of patient. However, systematical analysis of AS in lung squamous cell carcinoma (LUSC) is lacking and greatly necessary. Thus, this study was to systematically estimate the function of AS events served as prognostic indicators in LUSC. Among 31,345 mRNA AS events in 9633 genes, we detected 1996 AS in 1409 genes which have significant connection with overall survival (OS) of LUSC patients. Then, prognostic model based on seven types of AS events was established and we further constructed a combined prognostic model. The Kaplan–Meier curve results suggested that seven types of AS signatures and the combined prognostic model could exhibit robust performance in predicting prognosis. Patients in the high-risk group had significantly shorter OS than those in the low-risk group. The ROC showed all prognostic models had high accuracy and powerful predictive performance with different AUC ranging from 0.837 to 0.978. Moreover, the combined prognostic model had highest performance in risk stratification and predictive accuracy than single prognostic models and had higher accuracy than other mRNA model. Finally, a significant correlation network between survival-related AS genes and prognostic splicing factors (SFs) was established. In conclusion, our study provided several potential prognostic AS models and constructed splicing network between AS and SFs in LUSC, which could be used as potential indicators and treatment targets for LUSC patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12032-021-01490-1.

Profound understanding of the luminescence mechanism and structure-property relationship is vital for Cu(I) thermally activated delayed fluorescence (TADF) emitters. Herein, we theoretically simulated luminescent behavior in both solution and solid phases for two Cu(I) complexes and found the following: (i) The strengthened spin-orbit coupling (SOC) effect by more d

Several secure image encryption systems have been researched and formed by chaotic mechanisms in current decades. This work recommends an innovative quantum color image encryption method focused on the Lucas series-based substitution box to enhance the competence of encryption. The suggested encryption technique has more excellent key space and significant confidentiality. The chaotic system, along with the substitution box, exhibits additional complicated dynamical behavior, sufficient arbitrariness, and uncertainty than all others focused on just chaotic models. Theoretical and simulation assessments show that the offered image encryption performs admirably, its traditional equivalents in terms by efficiency in terms of statistical analysis.

Background To investigate the reference value of blood gas analysis and related factors in healthy adults in Diqing Tibetan Autonomous Prefecture in Yunnan Province. Methods From August 24, 2018 to August 11, 2020, healthy people between the ages of 18 and 70 years were observed at the Physical Examination Center of People's Hospital of Diqing Tibetan Autonomous Prefecture in Yunnan province. Participant information and clinical characteristics were collected. Blood gas analyzer was used to measure PH value, arterial partial oxygen pressure (PaO2), arterial partial pressure of carbon dioxide (PaCO2), arterial oxygen saturation (SaO2), acidity (pH), actual bicarbonate (AB) and residual base (BE). The participants' basic and blood gas indicator data were analyzed, and the blood gas reference values and related factors were analyzed using chi-squared tests, Mann-Whitney-Wilcoxon Test, and Spearman's correlation analysis. Results A total of 1,218 eligible health examination participants were included. They had an average age of 40 [31-47] years, and males accounted for 51.0%. In terms of blood gas reference values, the average pH value was moderate, and the values of PaO2, SaO2, PaCO2, AB, and BE were low. PaO2 was basically matched with the estimated value of the domestic model formula. These indexes were found to be correlated with social demographic characteristics such as sex, age, and smoking history. Conclusions The correlations between the indexes and social demographic characteristics may be helpful in the prediction of blood gas analysis results in clinical practice. For men, middle-aged and elderly people, or adults with a history of active smoking/biofuel exposure, blood gas PaO2 and PaCO2 should be monitored to facilitate the early intervention of respiratory failure. The PaO2 data basically matched the estimated values of the domestic model formula, suggesting that other regions in the Prefecture could use comprehensive epidemiological data and model methods to guide clinical work.

Ethnopharmacological relevance Thesium chinense Turcz. has been used to treat mastitis, pulmonitis, tonsillitis, iaryngopharyngitis and upper respiratory tract infections in the indigenous medicine of China for a long history. Presently, several pharmaceutics prepared by this medical herb have been clinically used for the therapy of infectious diseases. Aim of the review This review aims to comprehensively summarize the current researches on the ethnomedical, phytochemical and pharmacological aspects of T. chinense, and discuss their possible opportunities for the future research. Materials and methods Extensive database searches, including Web of Science, SciFinder, Google Scholar and China Knowledge Resource Integrated, were performed using keywords such as ‘Thesium chinense’, ‘Bai Rui Cao’, and their chemical constituents. In addition, local classic herbal literature on ethnopharmacology and relevant textbooks were consulted to provide a comprehensive survey of this ethnomedicine. Results Thirty four chemical constituents, including flavonoids, alkaloids, and terpenoids, have been identified from T. chinense. Of which, flavonoids are the predominant and characteristic constituents. The crude extracts, the purified constituents, and commercial available pharmaceutics have displayed diverse in vitro and in vivo pharmacological functions (e.g. anti-inflammation, antimicrobial activity, analgesic effect, hepaprotection), and are particularly useful as a potential therapeutic agent against inflammation-related diseases. Conclusions T. chinense is an important ethnomedical medicine and possesses a satisfying effect for treating inflammation, microbial infection, and upper respiratory diseases. It has received plenty of researches on its phytochemical and pharmacological aspects since 1970s. These findings definitely establish the link between chemical composition and pharmacological application, and support the ethnomedical use of T. chinense in the indigenous medicine of China. However, chemical composition of this plant and the molecular mechanisms of purified constituents have not been comprehensively investigated, and thus the trace constituents and the therapeutic targets of bioactive constituents deserve a further exploration. Collectively, the researchers should pay more attention to a better understanding and application of this ethnomedical plant.

Organic acids, as an important component of food, have great influence on the flavor, texture, freshness of food. By lowering the pH of food to bacteriostatic acidity, organic acids are also used as additives and preservatives. Because organic acids are crucial to predict and evaluate food maturity, production and quality control, the rapid and sensitive determination methods of organic acids are necessary. This review aims to summarize and update the progress of the determination of organic acids in food samples. Pretreatment methods include simple steps (e.g., "dilute and shoot," protein precipitation, filtration, and centrifugation) and advanced microextraction methods (e.g., hollow fiber liquid phase microextraction, stir bar sorptive extraction and dispersive micro-solid phase extraction). Advances in novel materials (nanomaterial), solvents (ionic liquids and supercritical fluids) and hybrid methods are clearly displayed in detail. Continuous progress which has been made in electrochemical method, two-dimensional chromatography, high resolution mass is thoroughly illustrated.

Benzimidazoles, commonly used as pesticides and veterinary drugs, have posed a threat to human health and the environment due to unreasonable use and lack of valid regulation. Therefore, an up-to-date and comprehensive summary of the pretreatment and analytical approaches in different substrates is urgently needed. The present review consequently updates and covers various newly developed pretreatment methods (e.g., cationic micellar precipitation, magnetic-solid phase extraction, hollow fiber liquid phase microextraction, disperse liquid-liquid microextraction-solidified floating organic drop, stir cake sorptive extraction, solid phase microextraction method, QuEChERS, and molecular imprinted polymer-based methods) since 2005. The review also elaborates and discusses different determination methods (e.g., newly developed HPLC and related methods, improved spectrofluorimetry methods, capillary electrophoresis, and the electrochemical sensor). Furthermore, some critical points and prospects are highlighted, to describe the trends in this area.

As highly toxic substances, N-nitrosamines (NAs) have been proved to cause carcinogenesis and mutagenesis in humans. Therefore, to carefully monitor safety and preserve human health, the development of rapid, accurate, and high-sensitivity determination methods of NAs is of substantial importance. This review provides a current-status comprehensive summary of the pretreatment and determination methods of NAs in various samples since 2010. Common pretreatment methods that have been used to extract and purify targets include solid-phase extraction, liquid-liquid extraction and various microextraction methods, such as solid-phase microextraction and liquid-phase microextraction, among others. Determination methods include liquid chromatography, gas chromatography, supercritical fluid chromatography and electrochemical methods, among others. In addition, we discuss and compare the advantages and disadvantages of various pretreatment and analytical methods and examine the prospects in this area.