In vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli in the mammalian gut.

The widespread sulfonamide resistance genes sul1, sul2, and sul3 in food and gut bacteria have attracted considerable attention. In this study, we assessed the in vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli, using a murine model. High fitness costs were incurred for sul1 and sul3 gene-dependent E. coli strains in vivo. A fitness advantage was found in three of the eight mice after intragastric administration of sul2 gene-dependent E. coli strains. We isolated three compensatory mutant strains (CMSs) independently from three mice that outcompeted the parent strain P2 in vivo. Whole-genome sequencing revealed seven identical single nucleotide polymorphism (SNP) mutations in the three CMSs compared with strain P2, an additional SNP mutation in strain S2-2, and two additional SNP mutations in strain S2-3. Furthermore, tandem mass tag-based quantitative proteomic analysis revealed abundant differentially expressed proteins (DEPs) in the CMSs compared with P2. Of these, seven key fitness-related DEPs distributed in two-component systems, galactose and tryptophan metabolism pathways, were verified using parallel reaction monitoring analysis. The DEPs in the CMSs influenced bacterial motility, environmental stress tolerance, colonization ability, carbohydrate utilization, cell morphology maintenance, and chemotaxis to restore fitness costs and adapt to the mammalian gut environment.IMPORTANCESulfonamides are traditional synthetic antimicrobial agents used in clinical and veterinary medical settings. Their long-term excessive overuse has resulted in widespread microbial resistance, limiting their application for medical interventions. Resistance to sulfonamides is primarily conferred by the alternative genes sul1, sul2, and sul3 encoding dihydropteroate synthase in bacteria. Studying the potential fitness cost of these sul genes is crucial for understanding the evolution and transmission of sulfonamide-resistant bacteria. In vitro studies have been conducted on the fitness cost of sul genes in bacteria. In this study, we provide critical insights into bacterial adaptation and transmission using an in vivo approach.

Reverse genetics construction and pathogenicity of a novel recombinant NADC30-like PRRSV isolated in China.

China has the largest pig herd in the world which accounts for more than 50% of the global pig population. Over the past three decades, the porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic loss to the Chinese swine industry. Currently, the prevalent PRRSV strains in the field are extremely complicated, and the NADC30-like strains, NADC34-like strains, and novel recombinant viruses have become a great concern to PRRS control in China. In this study, a novel NADC30-like PRRSV, named GS2022, was isolated from the lung of a dead pig collected from a farm that experienced a PRRS outbreak. The complete genome of GS2022 shares the highest identity with the NADC30 strain and contains a discontinuous deletion of 131 aa in nsp2. Novel deletion and insertion have been identified in ORF7 and 3'UTR. Recombination analysis revealed that the GS2022 is a potential recombinant of NADC30-like and JXA1-like strains. Both inter-lineage and intra-lineage recombination events were predicted to be involved in the generation of the GS2022. An infectious cDNA clone of GS2022 was assembled to generate the isogenic GS2022 (rGS2022). The growth kinetics of rGS2022 were almost identical to those of GS2022. The pathogenicity of the GS2022 and rGS2022 was evaluated using a nursery piglet model. In the infection groups, the piglets exhibited mild clinical symptoms, including short periods of fever and respiratory diseases. Both gross lesions and histopathological lesions were observed in the lungs and lymph nodes of the infected piglets. Therefore, we reported a novel recombinant NADC30-like PRRSV strain with moderate pathogenicity in piglets. These results provide new information on the genomic characteristics and pathogenicity of the NADC30-like PRRSV in China.

Vaginal microbiome differences between patients with adenomyosis with different menstrual cycles and healthy controls.

BACKGROUND: Adenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles. RESULTS: Differences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse. CONCLUSIONS: The vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.

Long COVID and its association with neurodegenerative diseases: pathogenesis, neuroimaging, and treatment.

Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca2+.

Initial study and phylogenetic analysis of hard ticks (Acari: Ixodidae) in Nantong, China along the route of avian migration.

The growing concern about migratory birds potentially spreading ticks due to global warming has become a significant issue. The city of Nantong in this study is situated along the East Asia-Australasian Flyway (EAAF), with numerous wetlands serving as roosting sites for migratory birds. We conducted an investigation of hard ticks and determined the phylogenetic characteristics of tick species in this city. We utilized three different genes for our study: the mitochondrial cytochrome oxidase subunit 1 (COX1) gene, the second internal transcribed spacer (ITS2), and the mitochondrial small subunit rRNA (12 S rRNA) gene. The predominant tick species were Haemaphysalis flava (H. flava) and Haemaphysalis longicornis (H. longicornis). Additionally, specimens of Haemaphysalis campanulata (H. campanulata) and Rhipicephalus sanguineus (R. sanguineus) were collected. The H. flava specimens in this study showed a close genetic relationship with those from inland provinces of China, as well as South Korea and Japan. Furthermore, samples of H. longicornis exhibited a close genetic relationship with those from South Korea, Japan, Australia, and the USA, as well as specific provinces in China. Furthermore, R. sanguineus specimens captured in Nantong showed genetic similarities with specimens from Egypt, Nigeria, and Argentina.

Serum Metabolites as Diagnostic Biomarkers in Patients with Endometriosis.

Endometriosis diagnosis is usually delayed. The gold standard for diagnosing endometriosis is laparoscopy, which is invasive and accompanied by several risks. Currently, there are no effective non-invasive biomarkers for diagnosing endometriosis. Here, we investigated whether metabolites whose levels are altered in patients with endometriosis hold potential as diagnostic biomarkers for the disease. This case-control study involved 32 patients with endometriosis and 29 patients with other benign gynecological disease. The diagnosis of all patients was confirmed through postoperative histopathological examination, and the patients were divided into two groups: an endometriosis group (EM) and a control group. Fasting blood was collected and used for non-targeted metabolomic-based detection. The data were processed through principal component analysis, orthogonal partial least squares discriminant analysis, and significance analysis of microarrays. A univariate receiver operating characteristic curve was used to evaluate the diagnostic value of the metabolites. The metabolite profiles of patients with endometriosis were markedly different compared with those of the controls. In addition, several metabolic pathways, including biosynthesis of unsaturated fatty acids, arginine biosynthesis, and glutathione metabolism, were altered. Ornithine and medorinone showed better potential as biomarkers for endometriosis diagnosis than CA125. We analyzed the altered metabolic profiles in patients with endometriosis and found ornithine and medorinone as potential non-invasive biomarkers for endometriosis diagnosis, whereas the combined ornithine-medorinone diagnosis is more valuable. These findings may help advance research on non-invasive diagnostic biomarkers for endometriosis. Further research with an improved study design and a larger cohort should be performed to confirm the diagnostic potential and clinical application of these biomarkers.

Two novel polysaccharides from Huangshui: Purification, structure, and bioactivities.

In this study, the novel polysaccharides named HSP-0 M and HSP-0.1 M were successfully purified from Huangshui (HS), and their structural properties and bioactivities were investigated. Structural analysis revealed that HSP-0 M had a molecular weight of 493.87 kDa and was composed of arabinose, galactose, glucose, xylose, and mannose in a molar ratio of 1.48:1.09:26.52:1.33:1.00. On the other hand, HSP-0.1 M was made up of fructose, arabinose, galactose, glucose, xylose, mannose, ribose, galacturonic acid and glucuronic acid in a ratio of 2.67:26.00:29.10:36.83:16.22:30.53:1.00:1.43:3.64 with a molecular weight of 157.6 kDa. Methylated and 2D NMR analyses indicated that T-Glcp-(1 â†’ 4)-Glcp-(1 â†’ 2)-Glcp-(1 â†’ 3)-Glcp was the primary chain of HSP-0 M, and the backbone of HSP-0.1 M was made up of →3)-Galp-(1 â†’ 6)-Manp-(1 â†’ 3)-Glcp-(1 â†’ 6)-Glcp-(1 â†’ 2)-Manp-(1 â†’ 6)-Glcp-(1 â†’ 3)-Galp. Morphological research showed that both polysaccharides were homogeneous as well as exhibit a web-like structure and an irregular lamellar structure. Furthermore, HSP-0 M demonstrated the capacity to safeguard Lactococcus lactis from damage caused by low temperatures and freeze-drying, while HSP-0.1 M exhibited noteworthy antioxidant activity. These results established a theoretical foundation for the applications of HSPs in food products, cosmetics, and medicines.

Evaluation of novel promoters for vascular tissue-specific gene expression in Populus.

Due to the extended generation cycle of trees, the breeding process for forest trees tends to be time-consuming. Genetic engineering has emerged as a viable approach to expedite the genetic breeding of forest trees. However, current genetic engineering techniques employed in forest trees often utilize continuous expression promoters such as CaMV 35S, which may result in unintended consequences by introducing genes into non-target tissues. Therefore, it is imperative to develop specific promoters for forest trees to facilitate targeted and precise design and breeding. In this study, we utilized single-cell RNA-Seq data and co-expression network analysis during wood formation to identify three vascular tissue-specific genes in poplar, PP2-A10, PXY, and VNS07, which are expressed in the phloem, cambium/expanding xylem, and mature xylem, respectively. Subsequently, we cloned the promoters of these three genes from '84K' poplar and constructed them into a vector containing the eyGFPuv visual selection marker, along with the 35S mini enhancer to drive GUS gene expression. Transgenic poplars expressing the ProPagPP2-A10::GUS, ProPagPXY::GUS, and ProPagVNS07::GUS constructs were obtained. To further elucidate the tissue specificity of these promoters, we employed qPCR, histochemical staining, and GUS enzyme activity. Our findings not only establish a solid foundation for the future utilization of these promoters to precisely express of specific functional genes in stems but also provide a novel perspective for the modular breeding of forest trees.

Use of statins and risks of ovarian, uterine, and cervical diseases: a cohort study in the UK Biobank.

PURPOSE: To examine the associations between use of statins and risks of various ovarian, uterine, and cervical diseases, including ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome, endometriosis, endometrial hyperplasia, endometrial polyp, and cervical polyp. METHODS: We conducted a cohort study among female participants in the UK Biobank. Information on the use of statins was collected through verbal interview. Outcome information was obtained by linking to national cancer registry data and hospital inpatient data. We used Cox proportional hazards regression to examine the associations. RESULTS: A total of 180,855 female participants (18,403 statin users and 162,452 non-users) were included. Use of statins was significantly associated with increased risks of cervical cancer (adjusted hazard ratio (HR), 1.55; 95% confidence interval (95% CI), 1.05-2.30) and polycystic ovarian syndrome (adjusted HR, 4.39; 95% CI, 1.68-11.49). However, we observed no significant association between use of statins and risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial hyperplasia, endometrial polyp, or cervical polyp. CONCLUSION: Our findings suggest that use of statins is associated with increased risks of cervical cancer and polycystic ovarian syndrome, but is not associated with increased or decreased risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial polyp, or cervical polyp.

Adverse drug reaction signal detection methods in spontaneous reporting system: A systematic review.

BACKGROUND: A series of signal detection methods have been developed to detect adverse drug reaction (ADR) signals in spontaneous reporting system. However, different signal detection methods yield quite different signal detection results, and we do not know which method has the best detection performance. How to choose the most suitable signal detection method is an urgent problem to be solved. In this study, we systematically reviewed the characteristics and application scopes of current signal detection methods, with the goal of providing references for the optimization selection of signal detection methods in spontaneous reporting system. METHODS: We searched six databases from inception to January 2023. The search strategy targeted literatures regarding signal detection methods in spontaneous reporting system. We used thematic analysis approach to summarize the advantages, disadvantages, and application scope of each signal detection method. RESULTS: A total of 93 literatures were included, including 27 reviews and 66 methodological studies. Moreover, 31 signal detection methods were identified in these literatures. Each signal detection method has its inherent advantages and disadvantages, resulting in different application scopes of these methods. CONCLUSION: Our systematic review finds that there are variabilities in the advantages, disadvantages, and application scopes of different signal detection methods. This finding indicates that the most suitable signal detection method varies across different drug safety scenarios. Moreover, when selecting signal detection method in a particular drug safety scenario, the following factors need to be considered: purpose of research, database size, drug characteristics, adverse event characteristics, and characteristics of the relations between drugs and adverse events.

Establishment of Comprehensive Protection System for Intellectual Property of Single Herbs by Taking Callicarpa nudiflora of Jiuzhitang as An Example / 中国实验方剂学杂志

The development of single Chinese materia medica is an important direction of technological innovation in the field of Chinese materia medica at present， and the study of its comprehensive intellectual property protection system is of great significance to the intellectual property protection of the whole chain of innovative enterprises of single Chinese materia medica. Based on this， this paper takes the comprehensive protection system of intellectual property of Callicarpa nudiflora constructed by Jiuzhitang Pharmaceutical as a model to conduct empirical research， analyzes the protection forms applicable to intellectual property of Chinese materia medica， such as patents， administrative protection， trademarks， designs and intangible cultural heritages， and discusses the valuable and insufficient aspects of the protection system currently constructed by Jiuzhitang Pharmaceutical and puts forward the following suggestions：①paying attention to patent applications for planting/processing methods of raw medicinal materials， ②emphasizing the protection of geographical indications， authentic medicinal herbs， and new plant varieties， ③actively promoting product and technology upgrades， ④applying for data protection during product iteration， ⑤emphasizing the layout timing of patent and administrative protection， ⑥focusing on improving goodwill， ⑦enhancing awareness of intellectual property protection and promoting deep integration of industry， academia， and research. We hope that innovative enterprises engaged in the development of single Chinese materia medica can learn from the experience of the case， and optimize the strategy to better protect related products.

Endometrial stromal cell autophagy-dependent ferroptosis caused by iron overload in ovarian endometriosis is inhibited by the ATF4-xCT pathway.

Ferroptosis is an iron-dependent programmed cell death process characterized by the accumulation of lethal oxidative damage. Localized iron overload is a unique clinical phenomenon in ovarian endometriosis (EM). However, the role and mechanism of ferroptosis in the course of ovarian EM remain unclear. Traditionally, autophagy promotes cell survival. However, a growing body of research suggests that autophagy promotes ferroptosis under certain conditions. This study aimed to clarify the status of ferroptosis in ovarian EM and explore the mechanism(s) by which iron overload causes ferroptosis and ectopic endometrial resistance to ferroptosis in human. The results showed increased levels of iron and reactive oxygen species in ectopic endometrial stromal cells (ESCs). Some ferroptosis and autophagy proteins in the ectopic tissues differed from those in the eutopic endometrium. In vitro, iron overload caused decreased cellular activity, increased lipid peroxidation levels, and mitochondrial morphological changes, whereas ferroptosis inhibitors alleviated these phenomena, illustrating activated ferroptosis. Iron overload increased autophagy, and ferroptosis caused by iron overload was inhibited by autophagy inhibitors, indicating that ferroptosis caused by iron overload was autophagy-dependent. We also confirmed the effect of iron overload and autophagy on lesion growth in vivo by constructing a mouse EM model; the results were consistent with those of the in vitro experiments of human tissue and endometrial stomal cells. However, ectopic lesions in patients can resist ferroptosis caused by iron overload, which can promote cystine/glutamate transporter hyperexpression by highly expressing activating transcription factor 4 (ATF4). In summary, local iron overload in ovarian EM can activate autophagy-related ferroptosis in ESCs, and ectopic lesions grow in a high-iron environment via ATF4-xCT while resisting ferroptosis. The effects of iron overload on other cells in the EM environment require further study. This study deepens our understanding of the role of ferroptosis in ovarian EM.

Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

Identification of a novel mutation of MBD5 gene in a pedigree affected with autosomal dominant mental retardation type 1 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with mental and motor retardation, language impairment, facial dysmorphism and epilepsy.@*METHODS@#Whole exome sequencing was carried out to detect pathogenic variant in the proband, and candidate variant was selected based on his phenotype. Sanger sequencing was used to verify the variant in the proband, his parents and other family members.@*RESULTS@#The proband was found to carry a frameshifting mutation of MBD5 gene, namely c.2217delT (p.F739Lfs*6), which was inherited from his mother and unreported previously. Sanger sequencing confirmed that his brother carried the same mutation with a similar phenotype. His mother also had poor language expression when she was young, in addition with poor academic performance, though she could do some housework and had no history of convulsion.@*CONCLUSION@#A novel pathogenic variant of the MBD5 gene was discovered, which has enriched the mutational spectrum of the MBD5 gene. Above discovery has enabled genetic counseling and prenatal diagnosis for the family.

Metabolic engineering strategies for de novo biosynthesis of sterols and steroids in yeast.

Steroidal compounds are of great interest in the pharmaceutical field, with steroidal drugs as the second largest category of medicine in the world. Advances in synthetic biology and metabolic engineering have enabled de novo biosynthesis of sterols and steroids in yeast, which is a green and safe production route for these valuable steroidal compounds. In this review, we summarize the metabolic engineering strategies developed and employed for improving the de novo biosynthesis of sterols and steroids in yeast based on the regulation mechanisms, and introduce the recent progresses in de novo synthesis of some typical sterols and steroids in yeast. The remaining challenges and future perspectives are also discussed.

Analysis of a family with asparagine synthase deficiency caused by ASNS gene mutation and literature review / 中华实用儿科临床杂志

Objective:To investigate the clinical characteristics and gene variation of asparagine synthase deficiency that is caused by ASNS gene variation. Methods:In Department of Neuroendocrine Pediatrics, Affiliated Hospital of Qingdao University from October 2018 to February 2020, the clinical data of a family of asparagine synthase deficiency were analyzed retrospectively.The pathogenic mutation of the proband was screened by the full exon analysis technique.The pathogenic sites of candidate genes were determined by combining the phenotype of the proband.In the heterotopic spot of the proband, his parents and other family members were verified by Sanger sequencing.Meanwhile, the relevant literature database was consulted, and the reported ASNS mutation related cases were collected and reviewed. Results:The female with proband visited the hospital at the age of 4 months, and she had recurrent convulsions at the age of about 3 months.Physical examination showed that the child suffered from microcephaly, and mental and motor retardation.Meanwhile, video electroencephalogram examination displayed extensive moderate high amplitude spiny slow wave and sharp slow wave.Exon sequencing illustrated that the compound heterozygous variants of ASNS gene were c. 1211G>A (p.R404H) and c. 1643C>T (p.S548F), respectively.c.1211G>A was a known pathogenic variant, and c. 1643C>T was a new variant.The proband′s younger brother visited the hospital at the age of 2 months, developed convulsions at the age of 1 month, and developed mental and motor retardation.Electroencephalogram displayed that bilateral posterior head was dominant, multiple foci and extensive spike wave, and spike slow wave and fast wave were distributed.Sanger sequencing revealed the same ASNS compound heterozygous variants as the proband.Both of them died of status convulsion at the age of 7 months and 6 months, respectively. Conclusions:This study is helpful to further understand the clinical features of the disease and reveal a new pathogenic mutation of ASNS gene, so as to enrich the mutation spectrum of ASNS gene, thus providing important basis for clinical treatment and genetic counseling.

Analysis of the effectiveness and safety of early radiotherapy intervention in oligometastatic non-small cell lung cancer / 中华放射医学与防护杂志

Objective:To investigate the prognostic factors of oligometastatic (OM) non-small cell lung cancer (NSCLC) patients and the safety and effectiveness of early radiotherapy intervention.Methods:A retrospective analysis was conducted, including 159 OM NSCLC cases (metastatic sites≤5, metastasis organs≤3) admitted to Department of Radiation Oncology in First Affiliated Hospital of Soochow University from January 2015 to December 2018. Among 159 cases, there were 107 males and 52 females, with the median age of 63 years. 137 cases were administrated via early radiotherapy intervention, and 22 cases via delayed radiotherapy intervention. The receiver operating characteristic curve (ROC) was used to determine the progression-free survival time (PFS)/overall survival time (OS) to ascertain the best cut-off value for local control and prognosis. Survival analysis was calculated by Kaplan-Meier curves, and Log rank test was used for comparison of these curves. Cox proportional hazards regression model was used for multivariate survival analysis.Results:The median follow-up time of 159 cases was 28.2 months. During the follow-up period, there were 16 cases with complete remission (10.1%), 53 cases with partial remission (33.3%), 27 cases with stable disease (17.0%), and 63 cases with progressed disease(39.6%). The local control rates at 3, 6 and 12 months were 83.9%, 59.7% and 41.0%, respectively. The median progression-free survival (PFS) of 159 patients was 8.0 months, the median survival time (OS) was 35.0 months, and 1, 2, and 3-year survival rates were 77.3%, 63.0% and 45.1%, respectively. Adverse reactions related to radiotherapy were relatively mild, mostly grade 1 and 2. PFS/OS= 0.3 is the best cut-off value for determining the patient′s local control and prognosis. The result of univariate analysis showed that gender, number of OM organs, T staging, radiotherapy intervention mode, tumor target volume absorbed dose (DT-GTVnx), PFS/OS were significantly related to median PFS ( χ2=4.175, 16.508, 4.408, 10.300, 6.842, 38.175, P<0.05); gender, pathological type, number of OM organs, initial diagnosis stage, T stage, N stage, lobectomy, radiotherapy intervention mode, tumor target volume (V-GTVnx), tumor load, local control status were significantly related to median OS ( χ2=6.672, 8.330, 21.299, 5.398, 6.874, 6.893, 5.611, 115.206, 4.017, 5.110, 21.299, P< 0.05). The result of multivariate analysis showed that delayed radiotherapy intervention ( HR=3.728, 95% CI 2.099-6.622, P<0.001) was an independent risk factor for PFS in patients with OM NSCLC, and PFS/OS>0.3 ( HR=0.123, 95% CI 0.062-0.246, P<0.001) was an independent protective factor for PFS in patients with OM NSCLC; male ( HR=1.665, 95% CI 1.024-3.043, P=0.033), high tumor burden ( HR=2.113, 95% CI 1.088-4.107, P=0.027), delayed radiotherapy interventions ( HR=15.076, 95% CI 7.925-28.680, P<0.001) were independent risk factors for OS in patients with OM NSCLC. Conclusions:OS of patients with OM NSCLC is significantly prolonged in female, low tumor burden and early radiotherapy intervention. Early radiotherapy intervention significantly improved the prognosis, and radiotherapy-related adverse reactions could be tolerated. These might suggest that local radiotherapy is safe and effective in the treatment of OM NSCLC patients.

Mechanism of Action of Trichosanthis Fructus-Allii Macrostemonis Bulbus Herb Pairs Against Hyperlipidemia Based on Network Pharmacology / 中国实验方剂学杂志

Objective:Based on the hyperlipidemia rat model and network pharmacology technology, the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia was analyzed. Method:The levels of blood lipids and inflammatory factors were measured through prophylactic administration of low, medium and high-dose Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs in hyperlipidemia rats. The active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs were screened out through Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and text mining. The targets of active ingredients screened through the Swiss Target Prediction, Similarity ensemble approach (SEA), DrugBank database. The disease targets were collected through Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), DrugBank, DisGeNET database. The targets of active ingredients and disease target were integrated, and screened through topological parameters to gain the main candidate targets of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the gene ontology (GO) functional enrichment analysis were conducted through ClueGO and Database for Annotation, Visualization and Integrated Discovery (DAVID), respectively. The traditional Chinese medicine-chemical ingredient-target network model, and the target-pathway network model were constructed through Cytoscape, and their crosstalk target and signal pathway were analyzed. Result:Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) in serum of rats with hyperlipidemia, increased high-density lipoprotein (HDL-C) levels, and inhibited the expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). According to the findings, 27 active ingredients, such as mandenol, diosmetin and α-spinasterol, might be the main active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs, 16 crosstalk targets and 10 signal pathways might be the main therapeutic targets and pathways, main targeting apolipoprotein A1 (APOA1), apolipoprotein A2 (APOA2), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL), low-density lipoprotein receptor (LDLR) and other crosstalk targets affected cholesterol metabolism, bile secretion, peroxisome proliferator activated receptor (PPAR) signaling pathway in regulating the lipid level, targeting tumor necrosis factor (TNF), IL-6, interleukin-1β (IL-1β), mitogen-activated protein kinase 1 (MAPK1), C-C motif chemokine 2 (CCL2) and other crosstalk targets affected tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway, interleukin-17 (IL-17) signaling pathway, and hypoxia inducible factor (HIF) signaling pathway in regulating the inflammatory factor level. The DAVID database for GO enrichment analysis showed that the hyperlipidemia was treated mainly through biological processes, such as inflammation, lipid localization, storage and lipid metabolism. Conclusion:These findings can predict the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia, and provide a theoretical basis for the material basis and clinical application of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs.

Strategy of nursing care on the face skin injuries caused by wearing medical-grade protective equipment / 中华烧伤杂志

For effective resistance to virus attack and infection, reducing virus transmission chance, it is extremely important for the medical staff and related workers to have their own safe protection. This paper summarizes the development causes, common locations, and prevention ways about the device related pressure injuries on the face resulted from wearing medical-grade protective equipment for a long working time. The paper proposes the nursing strategy for device related pressure injuries and other nursing strategy is proposed to take care efficiently the device related pressure injuries. Meantime, a corresponding nursing strategy is also suggested to deal with the correlative skin diseases during the application of medical-grade protective equipment. These paper aims to provide reference for the prevention of device related pressure injuries and the care of skin-related diseases for clinical working staff, especially to the respectable personnel in front line of fighting against Corona virus disease 2019.

Strategy of nursing care on the face skin injuries caused by wearing medical-grade protective equipment / 中华烧伤杂志

For effective resistance to virus attack and infection, reducing virus transmission chance, it is extremely important for the medical staff and related workers to have their own safe protection. This paper summarizes the development causes, common locations, and prevention ways about the device related pressure injuries on the face resulted from wearing medical-grade protective equipment for a long working time. The paper proposes the nursing strategy for device related pressure injuries and other nursing strategy is proposed to take care efficiently the device related pressure injuries. Meantime, a corresponding nursing strategy is also suggested to deal with the correlative skin diseases during the application of medical-grade protective equipment. These paper aims to provide reference for the prevention of device related pressure injuries and the care of skin-related diseases for clinical working staff, especially to the respectable personnel in front line of fighting against Corona virus disease 2019.