Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis.

Metastasis of colorectal cancer (CRC) is a leading cause of mortality among CRC patients. Elevated COX-2 and PD-L1 expression in colon cancer tissue has been linked to distant metastasis of tumor cells. Although COX-2 inhibitors and immune checkpoint inhibitors demonstrate improved anti-tumor efficacy, their toxicity and variable therapeutic effects in individual patients raise concerns. To address this challenge, it is vital to identify traditional Chinese medicine components that modulate COX-2 and PD-1/PD-L1: rosmarinic acid (RA) exerts striking inhibitory effect on COX-2, while ginsenoside Rg1 (GR) possesses the potential to suppress the binding of PD-1/PD-L1. In this study we investigated whether the combination of RA and GR could exert anti-metastatic effects against CRC. MC38 tumor xenograft mouse model with lung metastasis was established. The mice were administered RA (100 mg·kg-1·d-1, i.g.) alone or in combination with GR (100 mg·kg-1·d-1, i.p.). We showed that RA (50, 100, 150 µM) or a COX-2 inhibitor Celecoxib (1, 3, 9 µM) concentration-dependently inhibited the migration and invasion of MC38 cells in vitro. We further demonstrated that RA and Celecoxib inhibited the metastasis of MC38 tumors in vitro and in vivo via interfering with the COX-2-MYO10 signaling axis and inhibiting the generation of filopodia. In the MC38 tumor xenograft mice, RA administration significantly decreased the number of metastatic foci in the lungs detected by Micro CT scanning; RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1 further suppressed the lung metastasis of colon cancer. Compared to COX-2 inhibitors and immune checkpoint inhibitors, RA and GR displayed better safety profiles without disrupting the tissue structures of the liver, stomach and colon, offering insights into the lower toxic effects of clinical traditional Chinese medicine against tumors while retaining its efficacy.

Rapid Indentification of Auramine O Dyeing Adulteration in Dendrobium officinale, Saffron and Curcuma by SERS Raman Spectroscopy Combined with SSA-BP Neural Networks Model.

(1) Background: Rapid and accurate determination of the content of the chemical dye Auramine O(AO) in traditional Chinese medicines (TCMs) is critical for controlling the quality of TCMs. (2) Methods: Firstly, various models were developed to detect AO content in Dendrobium officinale (D. officinale). Then, the detection of AO content in Saffron and Curcuma using the D. officinale training set as a calibration model. Finally, Saffron and Curcuma samples were added to the training set of D. officinale to predict the AO content in Saffron and Curcuma using secondary wavelength screening. (3) Results: The results show that the sparrow search algorithm (SSA)-backpropagation (BP) neural network (SSA-BP) model can accurately predict AO content in D. officinale, with Rp2 = 0.962, and RMSEP = 0.080 mg/mL. Some Curcuma samples and Saffron samples were added to the training set and after the secondary feature wavelength screening: The Support Vector Machines (SVM) quantitative model predicted Rp2 fluctuated in the range of 0.780 ± 0.035 for the content of AO in Saffron when 579, 781, 1195, 1363, 1440, 1553 and 1657 cm-1 were selected as characteristic wavelengths; the Partial Least Squares Regression (PLSR) model predicted Rp2 fluctuated in the range of 0.500 ± 0.035 for the content of AO in Curcuma when 579, 811, 1195, 1353, 1440, 1553 and 1635 cm-1 were selected as the characteristic wavelengths. The robustness and generalization performance of the model were improved. (4) Conclusion: In this study, it has been discovered that the combination of surface-enhanced Raman spectroscopy (SERS) and machine learning algorithms can effectively and promptly detect the content of AO in various types of TCMs.

TFIIB-Related Protein BRP5/PTF2 Is Required for Both Male and Female Gametogenesis and for Grain Formation in Rice.

Transcription factor IIB (TFIIB) is a general transcription factor for RNA polymerase II, exerting its influence across various biological contexts. In the majority of eukaryotes, TFIIB typically has two homologs, serving as general transcription factors for RNA polymerase I and III. In plants, however, the TFIIB-related protein family has expanded greatly, with 14 and 9 members in Arabidopsis and rice, respectively. BRP5/pollen-expressed transcription factor 2 (PTF2) proteins belong to a subfamily of TFIIB-related proteins found only in plants and algae. The prior analysis of an Arabidopsis atbrp5 mutant, characterized by a T-DNA insertion at the 5' untranslated region, demonstrated the essential role of BRP5/PTF2 during the process of pollen germination and embryogenesis in Arabidopsis. Using a rice transformation system based on CRISPR/Cas9 technology, we have generated transgenic rice plants containing loss-of-function frameshift mutations in the BRP5/PTF2 gene. Unlike in the Arabidopsis atbrp5 mutant, the brp5/ptf2 frameshift mutations were not transmitted to progeny in rice, indicating an essential role of BRP5/PTF2 in both male and female gamete development or viability. The silencing of rice BRP5/PTF2 expression through RNA interference (RNAi) had little effect on vegetative growth and panicle formation but strongly affected pollen development and grain formation. Genetic analysis revealed that strong RNAi silencing of rice BRP5/PTF2 was still transmissible to progeny almost exclusively through female gametes, as found in the Arabidopsis atbrp5 knockdown mutant. Thus, reduced rice BRP5/PTF2 expression impacted pollen preferentially by interfering with male gamete development or viability. Drawing upon these findings, we posit that BRP5/PTF2 assumes a distinct and imperative function in the realm of plant sexual reproduction.

Integrating metabolomics and network pharmacology to assess the effects of quercetin on lung inflammatory injury induced by human respiratory syncytial virus.

Quercetin (QR) has significant anti-respiratory syncytial virus (RSV) effects. However, its therapeutic mechanism has not been thoroughly explored. In this study, a lung inflammatory injury model caused by RSV was established in mice. Untargeted lung tissue metabolomics was used to identify differential metabolites and metabolic pathways. Network pharmacology was used to predict potential therapeutic targets of QR and analyze biological functions and pathways modulated by QR. By overlapping the results of the metabolomics and the network pharmacology analyses, the common targets of QR that were likely to be involved in the amelioration of RSV-induced lung inflammatory injury by QR were identified. Metabolomics analysis identified 52 differential metabolites and 244 corresponding targets, while network pharmacology analysis identified 126 potential targets of QR. By intersecting these 244 targets with the 126 targets, hypoxanthine-guanine phosphoribosyltransferase (HPRT1), thymidine phosphorylase (TYMP), lactoperoxidase (LPO), myeloperoxidase (MPO), and cytochrome P450 19A1 (CYP19A1) were identified as the common targets. The key targets, HPRT1, TYMP, LPO, and MPO, were components of purine metabolic pathways. The present study demonstrated that QR effectively ameliorated RSV-induced lung inflammatory injury in the established mouse model. Combining metabolomics and network pharmacology showed that the anti-RSV effect of QR was closely associated with purine metabolism pathways.

Bufalin induces apoptosis and autophagy via the Ca2+/CaMKKß/AMPK/Beclin1 signaling pathway in osteosarcoma cells.

Bufalin, a major cardiotonic compound of the traditional Chinese medicine Chanshu has been used for cancer treatment for several years. However, the molecular mechanisms of Bufalin-induced autophagy in osteosarcoma (OS) is not fully understood. In the present study, it was shown that Bufalin induced crosstalk between apoptosis and autophagy, which resulted in OS cell death. Mechanistically, Bufalin induced autophagy by increased the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I, and inducing apoptosis via the caspase-dependent pathway. Inhibition of autophagy promoted Bufalin-induced cell death. In contrast, suppression of apoptosis enhanced Bufalin-induced autophagy. In addition, it was found that Bufalin activated the Ca2+ /calmodulin-dependent protein kinase ß/AMPK/Beclin1 pathway, which resulted in induction of autophagy. These findings provide a mechanistic understanding of the means by which Bufalin mediates autophagy and apoptosis in OS cells.

Diverse neolignans and lignans from an aqueous extract of the Angelica sinensis root head.

Neolignans and lignans with diverse new chemical structures, including eleven pairs of separated chiral enantiomers [(+)-/(-)-1-(+)-/(-)-5, (+)-/(-)-8, (+)-/(-)-10, and (+)-/(-)-12-(+)-/(-)-15], two achiral compounds (6 and 9), and an unseparated racemate [(±)-11], together with a new natural product (7) and 21 known derivatives, were isolated from an aqueous extract of the Angelica sinensis root head (guitou). Among the chiral isolates, (+)-/(-)-13 and (+)-/(-)-15 were scalemic pairs with enantiomeric ratios of around 3:1 and 1.5:1, respectively, while others were enantiomeric equivalent pairs. This indicates that the diverse neolignans in A. sinensis are biosynthesized via different pathways with varying degrees of stereo-controlled manners.

Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is associated with immunotherapy efficacy and survival in colorectal cancer.

BACKGROUND: Selenium-binding protein 1 (SELENBP1), a member of the selenium-containing protein family, plays an important role in malignant tumorigenesis and progression. However, it is currently lacking research about relationship between SELENBP1 and immunotherapy in colorectal cancer (CRC). METHODS: We first analyzed the expression levels of SELENBP1 based on the Cancer Genome Atlas (TCGA), Oncomine andUALCAN. Chisq.test, Fisher.test, Wilcoxon-Mann-Whitney test and logistic regression were used to analyze the relationship of clinical characteristics with SELENBP1 expression. Then Gene ontology/ Kyoto encyclopedia of genes and genomes (GO/KEGG), Gene set enrichment analysis (GSEA) enrichment analysis to clarify bio-processes and signaling pathways. The cBioPortal was used to perform analysis of mutation sites, types, etc. of SELENBP1. In addition, the correlation of SELENBP1 gene with tumor immune infiltration and prognosis was analyzed using ssGSEA, ESTIMATE, tumor immune dysfunction and rejection (TIDE) algorithm and Kaplan-Meier (KM) Plotter database. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to validate the expression of SELENBP1 in CRC samples and matched normal tissues. Immunohistochemistry (IHC) was further performed to detect the expression of SELENBP1 in CRC samples and matched normal tissues. RESULTS: We found that SELENBP1 expression was lower in CRC compared to normal colorectal tissue and was associated with poor prognosis. The aggressiveness of CRC increased with decreased SELENBP1 expression. Enrichment analysis showed that the SELENBP1 gene was significantly enriched in several pathways, such as programmed death 1 (PD-1) signaling, signaling by interleukins, TCR signaling, collagen degradation, costimulation by the CD28 family. Decreased expression of SELENBP1 was associated with DNA methylation and mutation. Immune infiltration analysis identified that SELENBP1 expression was closely related to various immune cells and immune chemokines/receptors. With increasing SELENBP1 expression, immune and stromal components in the tumor microenvironment were significantly decreased. SELENBP1 expression in CRC patients affects patient prognosis by influencing tumor immune infiltration. Beside this, SELENBP1 expression is closely related to the sensitivity of chemotherapy and immunotherapy. CONCLUSIONS: Survival analysis as well as enrichment and immunoassay results suggest that SELENBP1 can be considered as a promising prognostic biomarker for CRC. SELENBP1 expression is closely associated with immune infiltration and immunotherapy. Collectively, our study provided useful information on the oncogenic role of SELENBP1, contributing to further exploring the underlying mechanisms.

Salvianolic Acid A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting Neutrophil NETosis.

Salvianolic acid A (SAA) is one of bioactive polyphenol extracted from a Salvia miltiorrhiza (Danshen), which was widely used to treat cardiovascular disease in traditional Chinese medicine. SAA has been reported to be protective in cardiovascular disease and ischemia injury, with anti-inflammatory and antioxidative effect, but its role in acute lung injury (ALI) is still unknown. In this study, we sought to investigate the therapeutic effects of SAA in a murine model of lipopolysaccharide- (LPS-) induced ALI. The optimal dose of SAA was determined by comparing the attenuation of lung injury score after administration of SAA at three different doses (low, 5 mg/kg; medium, 10 mg/kg; and, high 15 mg/kg). Dexamethasone (DEX) was used as a positive control for SAA. Here, we showed that the therapeutic effect of SAA (10 mg/kg) against LPS-induced pathologic injury in the lungs was comparable to DEX. SAA and DEX attenuated the increased W/D ratio and the protein level, counts of total cells and neutrophils, and cytokine levels in the BALF of ALI mice similarly. The oxidative stress was also relieved by SAA and DEX according to the superoxide dismutase and malondialdehyde. NET level in the lungs was elevated in the injured lung while SAA and DEX reduced it significantly. LPS induced phosphorylation of Src, Raf, MEK, and ERK in the lungs, which was inhibited by SAA and DEX. NET level and phosphorylation level of Src/Raf/MEK/ERK pathway in the neutrophils from acute respiratory distress syndrome (ARDS) patients were also inhibited by SAA and DEX in vitro, but the YEEI peptide reversed the protective effect of SAA completely. The inhibition of NET release by SAA was also reversed by YEEI peptide in LPS-challenged neutrophils from healthy volunteers. Our data demonstrated that SAA ameliorated ALI via attenuating inflammation, oxidative stress, and neutrophil NETosis. The mechanism of such protective effect might involve the inhibition of Src activation.

[Identification, biological characteristics, and screening of effective fungicides of Phoma rhei causing leaf spot on Polygonum cuspidatum].

Severe leaf spot on Polygonum cuspidatum was found in the planting base of P. cuspidatum in Fangxian county, Shiyan of Hubei province. To clarify the types of pathogens and their pathogenesis, the present study isolated and purified the pathogen of leaf spot disease of P. cuspidatum according to Koch's postulates, determined the pathogenicity of the pathogen, and investigated its biological characteristics. Meanwhile, the inhibitory effects of 11 types of fungicides on the bacteria were determined according to the mycelium growth rate, and suitable prevention and control drugs were selected. The results showed that the pathogen isolated from the diseased leaves of P. cuspidatum was Phoma rhei by morphological and molecular identification. The colony morphology and microscopic characteristics were the same as those of Ph. rhei. The homology of rDNA-ITS and TEF gene sequences with Ph. rhei reached 99.96% and 99.43%, respectively. The optimal growth temperature of Ph. rhei was 25 ℃, and the optimal pH was 7-10. Furthermore, Ph. rhei grew faster under dark or light conditions. In fungicides, 0.3% eugenol, 250 g·L~(-1) propiconazole, and 33.5% quinoline copper had significant inhibitory effects on the pathogen with EC_(50) values of 57.54, 59.58, 88.69 µg·mL~(-1), respectively. Eugenol is a botanical fungicide, which can be used as a green and environmentally friendly fungicide in the prevention and control of P. cuspidatum. This study reported for the first time that the pathogen of P. cuspidatum leaf spot was Ph. rhei. investigated the biological characteristics of the pathogen, and screened the indoor chemicals, which provided a theoretical basis for the prevention and control of P. cuspidatum leaf spot in production.

Effectiveness of anisodamine for the treatment of critically ill patients with septic shock: a multicentre randomized controlled trial.

BACKGROUND: Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown. METHODS: In a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1-0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients' shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ2 test, Student's t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing. RESULTS: Of the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses-181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%; p = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28]; p = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6). CONCLUSIONS: There is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit. Trial registration ClinicalTrials.gov ( NCT02442440 ; Registered on 13 April 2015).

Mechanical Insights into Thiol-Mediated Synergetic Biotransformation of Cadmium and Selenium in Nematodes.

Cadmium ion (Cd2+) is a common environmental pollutant with high biotoxicity. Interestingly, the Cd2+ biotoxicity can be alleviated by the coexisting selenite (SeO32-), which induces the formation of cadmium selenide-rich nanoparticles (CdSe NPs) under the function of thiol-capping peptides. However, the detailed biochemical mechanisms by which Cd and Se are synergistically transformed into CdSe NPs in living organisms remain unclear so far. Here, we shed light on the molecular basis of such biotransformation processes in Caenorhabditis elegans by focusing on the roles of several key thiol-capping peptides. By monitoring the compositional and structural changes of the Cd and Se species and the genetic-level responses of nematodes, we revealed the specific roles of glutathione (GSH) and phytochelatins (PCs) in mediating the CdSe NP formation. With the aid of in vitro bioassembly assay and density functional theory calculations, the detailed Cd-Se interaction pathways were further deciphered: the ingested Cd binds predominantly to GSH and PCs in sequence, then further interacts with selenocysteine to form tetrahedral-structured PC2-Cd2-Sec2 complex, and ultimately grows into CdSe NPs. This work provides molecular-level insights into the Cd-Se interaction in C. elegans and lays a basis for controlling the ecological and health risks of heavy metals in polluted environment.

Minor triterpenes from an aqueous extract of the hook-bearing stem of Uncaria rhynchophylla.

Six new triterpenes, uncarinic acids KP (1-6), along with 24 known analogues, were isolated as minor constituents of an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). By comprehensive spectroscopic data analysis, their structures were elucidated as derivatives of olean-12-en-28-oic acid and urs-12-en-28-oic acid with different oxidized forms at C-3, C-6, and/or C-23, respectively. Cell-based preliminary bioassay showed that the (E)-/(Z)-coumaroyloxy and (E)-/(Z)-feruloyloxy units at C-27 of olean-12-en-28-oic acid and urs-12-en-28-oic acid played roles in their bioactivities.[Formula: see text].

A Stable Quaternized Chitosan-Black Phosphorus Nanocomposite for Synergetic Disinfection of Antibiotic-Resistant Pathogens.

Antibiotics are widely used for treatment of bacterial infections, and their overuse has contributed to microbial resistance. Currently, an alternative antibiotic-free therapy for inactivating bacteria is of great interest. Black phosphorus (BP), a biocompatible and nontoxic rising-star two-dimensional layered material, has gained remarkable interest in many bioapplications including biosensing, cancer therapy, drug delivery, and also antibacterial treatment. However, BP nanosheets suffer from instability in ambient environments due to rapid oxidation and degradation. To address this issue, BP nanosheets were modified with quaternized chitosan (QCS) by electrostatic adsorption to prepare a BP-QCS composite for photothermal/pharmaco treatment of bacterial infection. The BP-QCS has obviously enhanced solubility and chemical stability in aqueous suspensions. We have demonstrated that under near-infrared (NIR) irradiation, the BP-QCS can synergistically inactivate more than 95% methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) and Escherichia coli within 10 min with a dose of only 75 µg/mL in vitro. Meanwhile, the BP-QCS composite under NIR can synergistically inactivate 98% S. aureus in vivo. Furthermore, the BP-QCS suspensions at effective antibacterial concentrations have negligible cytotoxicity and in vivo toxicity.

[Effects of Artemisinin and Its Derivatives on Oral Microbes].

The oral environment provides suitable conditions for the colonization of various microorganisms. However, the oral microbials could be the initial factors of some kinds of oral infectious diseases, therefore the treatment against oral microbial pathogens has become an effective strategy. Artemisinin, a kind of sesquiterpene lactone extracted from Traditional Chinese Medicine Artemisia annua L., is the first-line therapy to treat tertian malaria, subtertian malaria and anti-chloroquine malaria for its high efficiency and low toxicity. In recent years, artemisinin and its derivatives have also been proven to be effective against bacteria, fungi, viruses, parasites, and tumors, some of which are closely related to oral diseases. In this review, we summarize the potential effects of artemisinin and its derivatives on oral microorganism by analyzing previous research and latest progress to provide the evidence for further improvement, and look forward to the new research directions. Further studies are needed to improve existing technologies and standards to clarify the effects of artemisinin and its derivatives on microorganisms with controversial effects, to expand the detection of microorganisms associated with oral infectious diseases, and to clarify the interaction with existing antifungal agents in the field of antifungal diseases. In addition, in the study of anti-oral infectious diseases, artemisinin and its derivatives' administration scheme, potential drug interactions, toxic and side effects and other aspects are necessary conditions for further research, which is also a new direction of research. With the maturity of the production process, the improvement of relevant research and the potential demand for the treatment of oral infectious diseases, artemisinin and its derivatives have a broad prospect in the field of oral microorganisms, and provide a new opportunity for the research and development of oral drugs.

Two folate-derived analogues from an aqueous decoction of Uncaria rhynchophylla.

Two new folate-derived analogues, named uncarophyllofolic acids A (1) and B (2), respectively, were isolated from the Uncaria rhynchophylla hook bearing stem (Gouteng in Chinese). The distinct stereochemical structures of 1 and 2 were determined by spectroscopic data analysis in combination with acidic hydrolysis and Marfey's derivatization, along with comparison of their specific rotation and Cotton effect (CE) data with those of the biogenetically related known derivatives as well as theoretical calculations of electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway of 1 and 2, associating to folate metabolism and the previously reported orychophragines A-C from Orychophragmus violaceus, is discussed.

Gastrodin Derivatives from Gastrodia elata.

Nine new gastrodin derivatives, including seven p-hydroxybenzyl-modified gastrodin ethers (1-7), 6'-O-acetylgastrodin (8), and 4-[α-D-glucopyranosyl-(1 →6)-ß-D-glucopyranosyloxy]benzyl alcohol (9), together with seven known derivatives, were isolated from an aqueous extract of Gastrodia elata ("tian ma") rhizomes. Their structures were determined by spectroscopic and chemical methods as well as single crystal X-ray diffraction. Compounds 1-4, 7, 10, and 11 were also isolated from a reaction mixture by refluxing gastrodin and p-hydroxybenzyl alcohol in H2O. As both gastrodin and p-hydroxybenzyl alcohol exist in the plant, the reaction results provide evidence for the production and increase/decrease of potential effective/toxic components when "tian ma" is decocted solely or together with ingredients in Chinese traditional medicine formulations, though the isolates were inactive in the preliminarily cell-based assays at concentrations of 10 µM. Moreover, using ultra-performance liquid chromatography high-resolution electrospray ionization mass spectrometry (UPLC-HRESIMS), 4, 7, 10, and 11, as well as component variations, were detectable in the freshly prepared extracts of different types of samples, including the freeze-dried fresh G. elata rhizomes.

Carbapenem-Resistant Klebsiella pneumoniae Infections among ICU Admission Patients in Central China: Prevalence and Prediction Model.

OBJECTIVE: To investigate the prevalence of infections due to carbapenem-resistant Klebsiella pneumoniae (CRKP) among ICU admission patients in central China and develop a reliable prediction model. METHODS: Five hundred and seven consecutive ICU admission patients with Klebsiella pneumoniae (KP) infection were enrolled in this retrospective multicenter case-control study from January 2014 to June 2018. The prevalence and antimicrobial susceptibility pattern were analyzed. Multivariate analysis was performed by logistic regression modeling to determine the risk factors. A prediction model was developed and verified using data from six hospitals in central China. RESULTS: Of the total 507 isolates of KP, 244 (48.1%) strains were carbapenem resistant. The majority of these isolates were from sputum (30.9%) and blood (20.9%) samples. Tigecycline had good activity against CRKP (95.5%). The most common sequence type (ST) of CRKP was ST11 (84.4%), and 98.6% of them had the blaKPC-2 antimicrobial resistance gene. Thirteen variables were identified as independent risk factors for CRKP infection, including KP colonization or infection in the preceding year (OR=3.32, 95% CI 2.01-4.38), CD4/CD8 ratio <1 (OR=2.98, 95% CI 2.02-4.19), and parenteral nutrition ⩾48 h (OR=1.88, 95% CI 1.22-3.04). The model developed to predict CRKP infection was effective, with an area under the receiver-operating characteristic curve of 0.854 (95% CI 0.821-0.884, p<0.001). CONCLUSIONS: ST11 carrying the blaKPC-2 antimicrobial resistance gene was the most common type of CRKP among the ICU admission patients in central China. The model demonstrated excellent predictive performance and exhibited good discrimination.

Antitumor and anti-inflammatory effects of oligosaccharides from Cistanche deserticola extract on spinal cord injury.

In the present study, the pharmacological effects of oligosaccharides from Cistanche deserticola extract on inflammation, oxidative stress, and apoptosis in male albino rats with spinal cord injury were investigated. Lipid peroxidation, GSH, catalase, superoxide dismutase, acetylcholine esterase, GPx, ROS, and nitric acid were significantly altered in the rats with spinal cord injury. The mRNA expression levels of IL-6, TNF-α, cyclooxygenase-2, iNOS, p53, caspase-3, bax, and pro-NGF were reduced by >20% following extract supplementation. Protein expression levels of caspase-3 and pro-NGF were also reduced by >20%. The number of p53 positive cells was 1, 79, 54, 33, and 19 in groups GI-GV, respectively, and the corresponding numbers of caspase-3 positive cells were 2, 87, 51, 23, and 14. Based on the present results, the use of oligosaccharides from Cistanche deserticola extract was effective against inflammation, oxidative stress, and apoptosis in spinal cord injury male albino rats.

Wet Cupping Therapy Improves Local Blood Perfusion and Analgesic Effects in Patients with Nerve-Root Type Cervical Spondylosis.

OBJECTIVE: To observe wet cupping therapy (WCT) on local blood perfusion and analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS). METHODS: Fifty-seven NT-CS patients were randomly divided into WCT group and Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group (30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated with acupuncture for 10 min. The treatment efficacies were evaluated with a Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB 21) acupoints (affected side) was observed with a laser speckle flowmetry, and its variations before and after treatment in both groups were compared as well. RESULTS: In both groups, the VAS scores significantly decreased after the intervention (P<0.01), while the blood perfusion at the two acupoints significantly increased after intervention (P<0.05); however, the increasement magnitude caused by WCT was obvious compared with JA (P<0.05). CONCLUSIONS: WCT could improve analgesic effects in patients with NT-CS, which might be related to increasing local blood perfusion of acupunct points.

Stimuli-Responsive "Cluster Bomb" for Programmed Tumor Therapy.

In this paper, mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and capped with tumor-homing/-penetrating peptide tLyP-1-modified tungsten disulfide quantum dots (WS2-HP) was designed and applied as a stimuli-responsive "Cluster Bomb" for high-performance tumor suppression. The peptide tLyP-1 on the surface can both facilitate the homing of DOX@MSN-WS2-HP to 4T1 tumor and greatly enhance the penetration of WS2-HP in tumor. The benzoic-imine bonds as the linkers between "bomblets" and "dispenser" are stable under normal physical conditions and quite labile at pH 6.8. After arriving at the mild acidic tumor microenvironment, the nanoplatform can rapidly break into two parts: (1) electropositive DOX@MSN-NH2 for efficient chemotherapy on surface tumor cells and (2) small-sized WS2-HP with improved tumor penetrating ability for near-infrared (NIR)-light-triggered photothermal therapy (PTT) among deep-seated tumor cells. Having killed the tumor cells in different depths, DOX@MSN-WS2-HP exhibited significant antitumor effect, which will find great potential in clinical trials.