MdWER interacts with MdERF109 and MdJAZ2 to mediate methyl jasmonate- and light-induced anthocyanin biosynthesis in apple fruit.

Anthocyanin generation in apples (Malus domestica) and the pigmentation that results from it may be caused by irradiation and through administration of methyl jasmonate (MeJA). However, their regulatory interrelationships associated with fruit coloration are not well defined. To determine whether MdERF109, a transcription factor (TF) involved in light-mediated coloration and anthocyanin biosynthesis, has synergistic effects with other proteins, we performed a yeast two-hybrid assessment and identified another TF, MdWER. MdWER was induced by MeJA treatment, and although overexpression of MdWER alone did not promote anthocyanin accumulation co-overexpression with MdERF109 resulted in significantly increase in anthocyanin biosynthesis. MdWER may form a protein complex with MdERF109 to promote anthocyanin accumulation by enhancing combinations between the proteins and their corresponding genes. In addition, MdWER, as a MeJA responsive protein, interacts with the anthocyanin repressor MdJAZ2. Transient co-expression in apple fruit and protein interaction assays allowed us to conclude that MdERF109 and MdJAZ2 interact with MdWER and take part in the production of anthocyanins upon MeJA treatment and irradiation. Our findings validate a role for the MdERF109-MdWER-MdJAZ2 module in anthocyanin biosynthesis and uncover a novel mechanism for how light and MeJA signals are coordinated anthocyanin biosynthesis in apple fruit.

Phosphorylation of MdERF17 by MdMPK4 promotes apple fruit peel degreening during light/dark transitions.

As apple fruits (Malus domestica) mature, they accumulate anthocyanins concomitantly with losing chlorophyll (Chl); however, the molecular pathways and events that coordinate Chl degradation and fruit coloration have not been elucidated. We showed previously that the transcription factor ETHYLENE RESPONSE FACTOR17 (MdERF17) modulates Chl degradation in apple fruit peels and that variation in the pattern of MdERF17 serine (Ser) residues is responsible for differences in its transcriptional regulatory activity. Here, we report that MdERF17 interacts with and is phosphorylated by MAP KINASE4 (MdMPK4-14G). Phosphorylation of MdERF17 at residue Thr67 by MdMPK4-14G is necessary for its transcriptional regulatory activity and its regulation of Chl degradation. We also show that MdERF17 mutants with different numbers of Ser repeat insertions exhibit altered phosphorylation profiles, with more repeats increasing its interaction with MdMPK4. MdMPK4-14G can be activated by exposure to darkness and is involved in the dark-induced degreening of fruit peels. We also demonstrate that greater phosphorylation of MdERF17 by MdMPK4-14G is responsible for the regulation of Chl degradation during light/dark transitions. Overall, our findings reveal the mechanism by which MdMPK4 controls fruit peel coloration.

The long noncoding RNA MdLNC499 bridges MdWRKY1 and MdERF109 function to regulate early-stage light-induced anthocyanin accumulation in apple fruit.

Anthocyanin pigments contribute to plant coloration and are valuable sources of antioxidants in the human diet as components of fruits and vegetables. Their production is known to be induced by light in apple fruit (Malus domestica); however, the underlying molecular mechanism responsible for early-stage light-induced anthocyanin biosynthesis remains unclear. Here, we identified an ethylene response factor (ERF) protein, ERF109, involved in light-induced anthocyanin biosynthesis and found that it promotes coloration by directly binding to anthocyanin-related gene promoters. Promoter::ß-glucuronidase reporter analysis and Hi-C sequencing showed that a long noncoding RNA, MdLNC499, located nearby MdERF109, induces the expression of MdERF109. A W-box cis-element in the MdLNC499 promoter was found to be regulated by a transcription factor, MdWRKY1. Transient expression in apple fruit and stable transformation of apple calli allowed us to reconstruct a MdWRKY1-MdLNC499-MdERF109 transcriptional cascade in which MdWRKY1 is activated by light to increase the transcription of MdLNC499, which in turn induces MdERF109. The MdERF109 protein induces the expression of anthocyanin-related genes and the accumulation of anthocyanins in the early stages of apple coloration. Our results provide a platform for better understanding the various regulatory mechanisms involved in light-induced apple fruit coloration.

Long-distance mobile mRNA CAX3 modulates iron uptake and zinc compartmentalization.

Iron deficiency in plants can lead to excessive absorption of zinc; however, important details of this mechanism have yet to be elucidated. Here, we report that MdCAX3 mRNA is transported from the leaf to the root, and that MdCAX3 is then activated by MdCXIP1. Suppression of MdCAX3 expression leads to an increase in the root apoplastic pH, which is associated with the iron deficiency response. Notably, overexpression of MdCAX3 does not affect the apoplastic pH in a MdCXIP1 loss-of-function Malus baccata (Mb) mutant that has a deletion in the MdCXIP1 promoter. This deletion in Mb weakens MdCXIP1 expression. Co-expression of MdCAX3 and MdCXIP1 in Mb causes a decrease in the root apoplastic pH. Furthermore, suppressing MdCAX3 in Malus significantly reduces zinc vacuole compartmentalization. We also show that MdCAX3 activated by MdCXIP1 is not only involved in iron uptake, but also in regulating zinc detoxification by compartmentalizing zinc in vacuoles to avoid iron starvation-induced zinc toxicity. Thus, mobile MdCAX3 mRNA is involved in the regulation of iron and zinc homeostasis in response to iron starvation.

Classification of benign and malignant pulmonary nodule based on local-global hybrid network.

BACKGROUND: The accurate classification of pulmonary nodules has great application value in assisting doctors in diagnosing conditions and meeting clinical needs. However, the complexity and heterogeneity of pulmonary nodules make it difficult to extract valuable characteristics of pulmonary nodules, so it is still challenging to achieve high-accuracy classification of pulmonary nodules. OBJECTIVE: In this paper, we propose a local-global hybrid network (LGHNet) to jointly model local and global information to improve the classification ability of benign and malignant pulmonary nodules. METHODS: First, we introduce the multi-scale local (MSL) block, which splits the input tensor into multiple channel groups, utilizing dilated convolutions with different dilation rates and efficient channel attention to extract fine-grained local information at different scales. Secondly, we design the hybrid attention (HA) block to capture long-range dependencies in spatial and channel dimensions to enhance the representation of global features. RESULTS: Experiments are carried out on the publicly available LIDC-IDRI and LUNGx datasets, and the accuracy, sensitivity, precision, specificity, and area under the curve (AUC) of the LIDC-IDRI dataset are 94.42%, 94.25%, 93.05%, 92.87%, and 97.26%, respectively. The AUC on the LUNGx dataset was 79.26%. CONCLUSION: The above classification results are superior to the state-of-the-art methods, indicating that the network has better classification performance and generalization ability.

MPK6-mediated HY5 phosphorylation regulates light-induced anthocyanin accumulation in apple fruit.

Light is known to regulate anthocyanin pigment biosynthesis in plants on several levels, but the significance of protein phosphorylation in light-induced anthocyanin accumulation needs further investigation. In this study, we investigated the dynamics of the apple fruit phosphoproteome in response to light, using high-performance liquid chromatography-tandem mass spectrometry analysis. Among the differentially phosphorylated proteins, the bZIP (basic leucine zipper) transcription factor, HY5, which has been identified as an anthocyanin regulator, was rapidly activated by light treatment of the fruit. We hypothesized that phosphorylated MdHY5 may play a role in light-induced anthocyanin accumulation of apple fruit. Protein interaction and phosphorylation assays showed that mitogen-activated protein kinase MdMPK6 directly interacted with, and activated, MdHY5 via phosphorylation under light conditions, thereby increasing its stability. Consistent with this finding, the suppression of the mitogen-activated protein kinase genes MdMPK6 or MdHY5 resulted in an inhibition of anthocyanin accumulation, and further showed that light-induced anthocyanin accumulation is dependent on MdMPK6 kinase activity, and is required for maximum MdHY5 activity. Under light conditions, active MdMPK6 phosphorylated MdHY5 leading to accumulation of phospho-MdHY5, which enhanced the binding of MdHY5 to its target anthocyanin related genes in fruit. Our findings reveal an MdMPK6-MdHY5 phosphorylation pathway in light-induced anthocyanin accumulation, providing new insights into the regulation of light-induced anthocyanin biosynthesis in apple fruit at both the transcriptional and post-translational levels.

A long noncoding RNA functions in high-light-induced anthocyanin accumulation in apple by activating ethylene synthesis.

Anthocyanin production in apple (Malus domestica) fruit and their consequent coloration can be induced by high-light treatment. The hormone ethylene is also essential for this coloration, but the regulatory relationships that link ethylene and light with anthocyanin-associated coloration are not well defined. In this study, we observed that high-light treatment of apple fruit increased anthocyanin accumulation more than moderate-light treatment did and was the main contributor of induced ethylene production and activation of anthocyanin biosynthesis. A transcriptome study of light-treated apple fruit suggested that a long noncoding RNA (lncRNA), MdLNC610, the corresponding gene of which is physically located downstream from the 1-aminocyclopropane-1-carboxylate oxygenase (ACO) ethylene biosynthesis gene MdACO1, likely affects anthocyanin biosynthesis under high-light treatment. Expression and promoter ß-glucuronidase reporter analyses further showed that MdLNC610 upregulates expression of MdACO1 and so likely participates in high-light-induced ethylene biosynthesis. Overexpression of MdACO1 and MdLNC610 in apple fruit and calli indicated that a major increase in MdLNC610 expression activates MdACO1 expression, thereby causing an increase in ethylene production and anthocyanin levels. These results suggest that MdLNC610 participates in the regulation of high-light-induced anthocyanin production by functioning as a positive regulator to promote MdACO1 expression and ethylene biosynthesis. Our study provides insights into the relationship between mRNA and lncRNA networks in the ethylene biosynthetic pathway and anthocyanin accumulation in apple fruit.

Ethylene response factor MdERF4 and histone deacetylase MdHDA19 suppress apple fruit ripening through histone deacetylation of ripening-related genes.

Histone deacetylase enzymes participate in the regulation of many aspects of plant development. However, the genome-level targets of histone deacetylation during apple (Malus domestica) fruit development have not been resolved in detail, and the mechanisms of regulation of such a process are unknown. We previously showed that the complex of ethylene response factor 4 (MdERF4) and the TOPLESS co-repressor (MdTPL4; MdERF4-MdTPL4) is constitutively active during apple fruit development (Hu et al., 2020), but whether this transcriptional repression complex is coupled to chromatin modification is unknown. Here, we show that a histone deacetylase (MdHDA19) is recruited to the MdERF4-MdTPL4 complex, thereby impacting fruit ethylene biosynthesis. Transient suppression of MdHDA19 expression promoted fruit ripening and ethylene production. To identify potential downstream target genes regulated by MdHDA19, we conducted chromatin immunoprecipitation (ChIP) sequencing of H3K9 and ChIP-quantitative polymerase chain reaction assays. We found that MdHDA19 affects ethylene production by facilitating H3K9 deacetylation and forms a complex with MdERF4-MdTPL4 to directly repress MdACS3a expression by decreasing the degree of acetylation. We demonstrate that an early-maturing-specific acetylation H3K9ac peak in MdACS3a and expression of MdACS3a were specifically up-regulated in fruit of an early-maturing, but not a late-maturing, cultivar. We provide evidence that a C-to-G mutation in the ethylene-responsive element binding factor-associated amphiphilic repression motif of MdERF4 reduces the repression of MdACS3a by the MdERF4-MdTPL4-MdHDA19 complex. Taken together, our results reveal that the MdERF4-MdTPL-MdHDA19 repressor complex participates in the epigenetic regulation of apple fruit ripening.

Ectopic invasive ACTH-secreting pituitary adenoma mimicking chordoma: a case report and literature review.

BACKGROUND: Ectopic pituitary adenoma (EPA) is defined as a special type of pituitary adenoma that originates outside of the sellar region, is extra- or intra-cranially located, and without connection to normal pituitary tissue. EPA is extremely rare, with most cases presented as case reports or small case series. Due to nonspecific symptoms and laboratory indicators, the preoperative diagnosis, treatment and management for EPA remain challenging. CASE PRESENTATION: Here, we report the imaging phenotype and pathological findings of a case of invasive EPA in a 47-year-old woman. A preoperative non-contrast CT scan revealed a 5.8 × 3.6 × 3.7 cm soft tissue mass located in the sphenoid sinus and clivus. MRI showed an ill-defined solid mass with heterogeneous signals on T1-weighted and T2-weighted images. The mass displayed infiltrative growth pattern, destroying bone of the skull base, invading adjacent muscles and encasing vessels. The patient underwent partial tumor resection via transsphenoidal endoscopic surgery. Pathological examination led to diagnosis of ectopic ACTH-secreting pituitary adenoma. Post-surgery, the patient received external beam radiotherapy. CONCLUSION: EPA with invasive growth pattern has rarely been reported. The imaging phenotype displays its relationship to the pituitary tissue and surrounding structures. Immunohistochemical examination acts as a crucial role in differentiating EPA from other skull base tumors. This case report adds to the literature on EPA by summarizing its characteristics alongside a review of the literature.

Quercetin-3-O-α-L-arabinopyranosyl-(1→2)-ß-D-glucopyranoside Isolated from Eucommia ulmoides Leaf Relieves Insulin Resistance in HepG2 Cells via the IRS-1/PI3K/Akt/GSK-3ß Pathway.

For nearly 2000 years, Eucommia ulmoides Oliver (EUO) has been utilized in traditional Chinese medicine (TCM) throughout China. Flavonoids present in bark and leaves of EUO are responsible for their antioxidant, anti-inflammatory, antitumor, anti-osteoporosis, hypoglycemic, hypolipidemic, antibacterial, and antiviral properties, but the main bioactive compound has not been established yet. In this study, we isolated and identified quercetin glycoside (QAG) from EUO leaves (EUOL) and preliminarily explored its molecular mechanism in improving insulin resistance (IR). The results showed that QAG increased uptake of glucose as well as glycogen production in the palmitic acid (PA)-induced HepG2 cells in a dose-dependent way. Further, we observed that QAG increases glucose transporters 2 and 4 (GLUT2 and GLUT4) expression and suppresses the phosphorylation of insulin receptor substrate (IRS)-1 at serine612, thus promoting the expression of phosphatidylinositol-3-kinase (PI3K) at tyrosine458 and tyrosine199, as well as protein kinase B (Akt) and glycogen synthase kinase (GSK)-3ß at serine473 and serine9, respectively. The influence posed by QAG on the improvement of uptake of glucose was significantly inhibited by LY294002, a PI3K inhibitor. In addition, the molecular docking result showed that QAG could bind to insulin receptors. In summary, our data established that QAG improved IR as demonstrated by the increased uptake of glucose and glycogen production through a signaling pathway called IRS-1/PI3K/Akt/GSK-3ß.

Oral hydrogel nanoemulsion co-delivery system treats inflammatory bowel disease via anti-inflammatory and promoting intestinal mucosa repair.

BACKGROUND: Due to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it's urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon. RESULTS: In this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment. CONCLUSIONS: It's suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD.

Apple MPK4 mediates phosphorylation of MYB1 to enhance light-induced anthocyanin accumulation.

Anthocyanins are plant pigments with diverse biological functions that contribute to fruit quality and are beneficial to human health. Anthocyanin accumulation can be influenced by environmental signals, such as light, and plants have developed sophisticated systems to receive and transduce these signals. However, the associated molecular mechanisms are not well understood. In this study, we investigated the potential function of mitogen-activated protein kinases, which are members of the light signaling pathway, during light-induced anthocyanin accumulation in apple (Malus domestica) fruit peels. An antibody array and yeast two-hybrid screen indicated that proteins encoded by two MdMPK4 genes are light-activated and interact with the transcription factor and anthocyanin biosynthesis regulator MdMYB1. A phosphorylation assay showed that the MdMPK4 proteins phosphorylate MdMYB1, thereby increasing its stability under light conditions. Transient MdMPK4 and MdMYB1 overexpression assays further revealed that light-induced anthocyanin accumulation relies on MdMPK4 kinase activity, which is required for maximum MdMYB1 activity. Based on the expression of the chromosome 6 allele MdMPK4-06G under light conditions and the presence of light response elements in the MdMPK4-06G promoter, we concluded that it is more responsive to light than the chromosome 14 allele MdMPK4-14G. These results suggest a potential biotechnological strategy for increasing fruit anthocyanin content via light induction.

RBP differentiation contributes to selective transmissibility of OPT3 mRNAs.

Long-distance mobile mRNAs play key roles in gene regulatory networks that control plant development and stress tolerance. However, the mechanisms underlying species-specific delivery of mRNA still need to be elucidated. Here, the use of grafts involving highly heterozygous apple (Malus) genotypes allowed us to demonstrate that apple (Malus domestica) oligopeptide transporter3 (MdOPT3) mRNA can be transported over a long distance, from the leaf to the root, to regulate iron uptake; however, the mRNA of Arabidopsis (Arabidopsis thaliana) oligopeptide transporter 3 (AtOPT3), the MdOPT3 homolog from A. thaliana, does not move from shoot to root. Reciprocal heterologous expression of the two types of mRNAs showed that the immobile AtOPT3 became mobile and moved from the shoot to the root in two woody species, Malus and Populus, while the mobile MdOPT3 became immobile in two herbaceous species, A. thaliana and tomato (Solanum lycopersicum). Furthermore, we demonstrated that the different transmissibility of OPT3 in A. thaliana and Malus might be caused by divergence in RNA-binding proteins between herbaceous and woody plants. This study provides insights into mechanisms underlying differences in mRNA mobility and validates the important physiological functions associated with this process.

Halomonas profundi sp. nov., isolated from deep-sea sediment of the Mariana Trench.

Two novel Gram-stain-negative, facultative anaerobic, non-flagellated, rod-shaped bacterial strains, designated MT13T and MT32, were isolated from sediment samples collected from the Mariana Trench at a depth of 8300 m. The two strains grew at -2-30 °C (optimum, 25 °C), at pH 5.5-10.0 (optimum, pH 7.5-8.0) and with 0-15 % (w/v) NaCl (optimum, 3-6 %). They did not reduce nitrate to nitrite nor hydrolyse Tweens 40 and 80, aesculin, casein, starch and DNA. The genomic G+C contents of draft genomes of strain MT13T and MT32 were 52.2 and 54.1 m ol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains MT13T and MT32 were affiliated with the genus Halomonas, with the highest similarity to the type strain of Halomonas olivaria. The values of average nucleotide identity and in silico DNA-DNA hybridization between strain MT13T and MT32, and between strain MT13T and five closely related type strains of Halomonas species indicated that strains MT13T and MT32 belonged to the same species, but represented a novel species in the genus of Halomonas. The major cellular fatty acids of strains MT13T and MT32 were C16 : 0, summed feature 3(C16 : 1 ω7c/ω6c) and summed feature 8 (C18 : 1 ω7c/ω6c). Major polar lipids of strains MT13T and MT32 included phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol. Ubiquinone-9 was the predominant respiratory quinone. Based on data from the present polyphasic study, strains MT13T and MT32 represent a novel species of the genus Halomonas, for which the name Halomonas profundi sp. nov. is proposed. The type strain is MT13T (=MCCC 1K06389T=KCTC 82923T).

Drug therapy for bone metastasis of malignant tumor: theory, progress, and potential.

Bone is a common metastatic site of malignancies, caused by the complex interaction between tumor cells and the bone microenvironment. The complicated procedure covers multiple targets for therapeutic strategies against bone metastasis. At the present, only bisphosphonates and denosumab are currently approved for the prevention of skeletal-related events. But it is still ineffective for some patients, and none of them are proven to prolong the overall survival of patients with bone metastasis. Thus, new bone-modifying agents and therapeutic strategies are required. The review aimed to generalize the basic theory of bone metastasis and major put emphasis on the development of fundamental and potential target drugs in the behavior of bone metastasis. The summary of the drug development process helps to provide ideas for finding new and effective treatments for bone metastasis.

Effects of a teaching mode combining SimBaby with standardized patients on medical students' attitudes toward communication skills.

OBJECTIVE: To evaluate the effect of a teaching mode combining SimBaby with standardized patients (SP) on medical students' attitudes toward communication skills (CS). METHODS: Forty 8-year medical program students majoring in clinical medicine were randomly divided into the SimBaby group (n = 20) and the SP + SimBaby group (n = 20). The Communication Skills Attitude Scale (CSAS) was used to evaluate medical students' attitudes toward CS learning. RESULTS: In the SimBaby and SP + SimBaby groups, there were no statistically significant differences in the Positive Attitude Subscale (PAS) and Negative Attitude Subscale (NAS) scores between males and females (p > 0.05). Compared to the SimBaby group, the SP + SimBaby group showed statistically significant differences in PAS, NAS, and the two dimensions of importance in medical context and learning (p < 0.05). There were no statistically significant differences between groups in the dimensions of excusing and overconfidence (p > 0.05). CONCLUSION: Compared with SimBaby alone, the SP + SimBaby teaching mode can improve medical students' attitude toward CS learning, suggesting that the organic integration of multiple simulation-based medical teaching methods plays an important role in the acquisition of CS.

A long non-coding apple RNA, MSTRG.85814.11, acts as a transcriptional enhancer of SAUR32 and contributes to the Fe-deficiency response.

Iron (Fe) is an essential plant nutrient and its deficiency typically limits plant growth. Long non-coding (lnc) RNAs are involved in adaptive responses to nutrient stress; however, it is not known whether they function in the regulation of the canonical Fe-deficiency response. The expression of Malus domestica (apple) lncRNA MSTRG.85814 is induced by Fe deficiency, as identified by high-throughput strand-specific RNA-seq analysis of an apple homograft system. MSTRG.85814 has a complex structure, with 13 predicted RNA sequence variants, four of which are upregulated in the roots of plants experiencing Fe deficiency. We found that one MSTRG.85814 splice variant (MSTRG.85814.11) positively modulated its cis target mRNA derived from the small auxin upregulated gene SAUR32. This in turn promoted the expression of SAUR32 and caused an increase in the expression of a plasma membrane proton ATPase, AHA10. Using a pH imaging technique, a significant decrease in the apoplastic pH was observed to occur in the root tips of MSTRG.85814.11 or SAUR32-overexpressing apple plants. Thus MSTRG.85814.11 was shown to positively promote SAUR32 expression, which then activated proton extrusion involved in the Fe-deficiency response. These results reveal a mechanism by which lncRNA promotes environmental Fe-deficiency stress adaption.

Iliac ecchymosis, a valuable sign for hollow viscus injuries in blunt pelvic trauma patients.

PURPOSE: Pelvic fractures are characterized by high energy injuries and often accompanied with abdominal and pelvic organ injury. CT has been applied for several decades to evaluate blunt pelvic trauma patients. However, it has a certain rate of inaccurate diagnosis of abdominal hollow viscus injury (HVI), especially in the early stage after injury. The delayed diagnosis of HVI could result in a high morbidity and mortality. The bowel injury prediction score (BIPS) applied 3 clinical variables to determine whether an early surgical intervention for blunt HVI was necessary. We recently found another clinical variable (iliac ecchymosis, IE) which appeared at the early stage of injury, could be predicted for HVI. The main objective of this study was to explore the novel combination of IE and BIPS to enhance the early diagnosis rate of HVI, and thus reduce complications and mortalities. METHODS: We conducted a retrospective analysis from January 2008 to December 2018 and recorded blunt pelvic trauma patients in our hospital. The inclusion criteria were patients who were verified with pelvic fractures using abdomen and pelvis CT scan in the emergency department before any surgical intervention. The exclusion criteria were abdominal CT insufficiency before operation, abdominal surgery before CT scan, and CT mesenteric injury grade being 5. The MBIPS was defined as BIPS plus IE, which was calculated according to 4 variables: white blood cell counts of 17.0 or greater, abdominal tenderness, CT scan grade for mesenteric injury of 4 or higher, and the location of IE. Each clinical variable counted 1 score, totally 4 scores. The location and severity of IE was also noted. RESULTS: In total, 635 cases were hospitalized and 62 patients were enrolled in this study. Of these included patients, 77.4% (40 males and 8 females) were operated by exploratory laparotomy and 22.6% (8 males and 6 females) were treated conservatively. In the 48 patients underwent surgical intervention, 46 were confirmed with HVI (45 with IE and 1 without IE). In 46 patients confirmed without HVI, only 3 patients had IE and the rest had no IE. The sensitivity and specificity of IE in predicting HVI was calculated as 97.8% (45/46) and 81.3% (13/16), respectively. The median MBIPS score for surgery group was 2, while 0 for the conservative treatment group. The incidence of HVI in patients with MBIPS score ≥ 2 was significantly higher than that in patients with MBIPS score less than ≤ 2 (OR = 17.3, p < 0.001). CONCLUSION: IE can be recognized as an indirect sign of HVI because of the high sensitivity and specificity, which is a valuable sign for HVI in blunt pelvic trauma patients. MBIPS can be used to predict HVI in blunt pelvic trauma patients. When the MBIPS score is ≥ 2, HVI is strongly suggested.

[Study on potential effective components and mechanism of Zhishe Tongluo Capsules in treatment of ischemic stroke].

To explore the potential effective components and mechanism of Zhishe Tongluo Capsules in the treatment of ischemic stroke via network pharmacology, molecular docking and cellular experiment. The chemical constituents of Zhishe Tongluo Capsules were found by TCMSP, BATMAN-TCM and literatures. The constituents-target network was predicted by BATMAN-TCM database. Key words such as cerebral stroke, ischemic stroke and cerebral ischemic stroke were used to search ischemic stroke related targets, and then Venny Map was constructed based on the targets of traditional Chinese medicine and the targets of ischemic stroke. The overlapping targets were imported into STRING database to establish the interaction network. Furthermore, the core targets were screened out by Cytoscape software. Go and KEGG enrichment analysis were performed through DVIAD database. The results showed a total of 193 potential chemical constituents, 985 drug targets and 6 035 disease targets. There were 631 potential targets, 44 core targets and 55 potential active components for treating ischemic stroke through Venny mapping. GO enrichment analysis mainly involved response to hypoxia and positive regulation of ERK1/ERK2. KEGG pathway enrichment analysis mainly involved cholinergic synapse, cAMP signaling pathway, and calcium signaling pathway. Molecular docking data revealed that TP53, EGFR, IL6, INS, TNF and SRC had a good capability to bind with their corresponding active components. To ensure the protective effect Zhishe Tongluo Capsules on the inflammation reaction, an in vitro model of lipopolysaccharide(LPS)-induced RAW264.7 cells was built. The contents of IL-1α, IL-1ß, IL-6 and TNF-α in the supernatant were significantly decreased by enzyme linked immunosorbent assay(ELISA). The findings suggested that Zhishe Tongluo Capsules could prevent the injury of ischemic stroke by inhibiting the inflammation.

[A novel flavanone from Thymus przewalskii].

This study was to investigate the chemical constituents from the aerial parts of Thymus przewalskii. The chemical consti-tuents were separated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and semi-prepared HPLC, and their structures were determined by physicochemical properties and spectroscopic data. Four flavanones were isolated from the ethanol extract of the aerial parts of T. przewalskii, and identified as(2S)-5,6-dihydroxy-7,8,4'-trimethoxyflavanone(1), 5,4'-dihydroxy-6,7-dimethoxyflavanone(2),(2S)-5,4'-dihydroxy-7,8-dimethoxyflavanone(3), sakuranetin(4), respectively. Compound 1 was a new compound and its configuration was determined by CD spectrum, compound 3 was natural product which was isolated for the first time and their configurations were determined by CD spectra. Compound 2 was isolated from the genus Thymus for the first time and compound 4 was isolated from T. przewalskii for the first time. Furthermore, cytotoxicity test was assayed for the four flavanones. They exhibited weak cytotoxicity against human lung cancer cells(A549), with the IC_(50) from 74.5 to 135.6 µmol·L~(-1).