First Report of Fusarium falciforme Causing Root and Rhizome Rot of Epimedium sagittatum in China.

Epimedium sagittatum (Sieb.et Zucc.) Maxim., a perennial herb, is an important medicinal plant, rich in flavonoids, and widely used in the treatment of sexual dysfunction, rheumatic disease, and cancers (Tan et al. 2016). In July 2022, a disease of root and rhizome was found on E. sagittatum aged 1-8 years in a planting area (266 ha) of Zhumadian City (32°58'12" N, 114°37'48" E), Henan Province, China. The disease incidence per field (660 m2) was around 10-15% in six randomly surveyed fields planted with about 10,000 E. sagittatum plants each. Symptoms included leaf yellowing, root and rhizome browning, rotting and necrosis, and eventually the whole plant wilted and died. Fifteen plants with symptoms were sampled to isolate the pathogen. Symptomatic tissues were cut into small pieces of 5×5 mm, surface sterilized with 75% ethanol for 30 s, followed by three rinses with sterile double-distilled water (ddH2O). The pieces were then surface disinfected with 0.1% HgCl2 for 30 s, rinsed three times with sterile ddH2O, placed onto potato dextrose agar (PDA) plates and incubated at 28°C in the dark for 5 days. Twelve deferent Fusarium spp. colonies were purified by excising hyphal tip onto PDA for cultivation. Pathogenicity test of all strains was performed. Only isolate GY2 could result in root and rhizome rot of host plant. Colonies of GY2 on PDA had abundant white aerial mycelia with yellow halo. Macroconidia were hyaline, falciform, with a slightly curved apical cell and blunt basal cell, 29.7~45.0 (average 38.3) × 4.5~6.6 (average 5.3) µm (n =50), with 2-3 septa. Microconidia were oval, or reniform, hyaline, 8.4~26.5 (average 16.5) × 2.7~6.0 (average 4.5) µm (n =50), with 0-2 septa. Morphological characteristics of isolate GY2 were consistent with those of the Fusarium solani species complex (FSSC) (Chehri et al. 2015). For molecular identification, a region of the translation elongation factor 1-α (TEF) and RNA polymerase second largest subunit (RPB2) of GY2 were PCR-amplified and sequenced using the primers EF1-728F/986R (Carbone et al. 1999) and RPB2-5f2/7cr (O'Donnell et al. 2010), respectively. The TEF and RPB2 sequences (GenBank accession nos. OR978135.1 and OR978136.1) of GY2 were concatenated for a phylogenetic analysis using the Bayesian method (Zhang et al. 2020). The phylogenetic tree revealed that isolate GY2 clustered with F. falciforme with a credibility value of 99%. Morphological and molecular results support identification of isolate GY2 as F. falciforme. A pathogenicity test was performed on 4-year-old healthy plants grown in pots. Twenty healthy plants were inoculated by pouring a 200 mL conidial suspension (1×106 conidia/mL) around the rhizome. Control plants received 200 mL of sterile ddH2O. All treatments were maintained in a greenhouse at 25±1°C and 80% relative humidity. The assay was conducted three times. After 20 days, similar symptoms as those in the field were observed on the inoculated plants, whereas controls remained asymptomatic. Fusarium falciforme was reisolated from the symptomatic plants and showed the same morphological and molecular characteristics as isolate GY2, fulfilling Koch's postulates. Fusarium falciforme was reported to cause root rot of tobacco (Qiu et al. 2023) and industrial hemp (Paugh et al. 2022). However, this is the first report of F. falciforme causing root and rhizome rot of E. sagittatum. Our study will contribute to the development of strategies for the effective management of this disease on E. sagittatum.

Network pharmacology and experimental validation to investigate the mechanism of Nao-Ling-Su capsule in the treatment of ischemia/reperfusion-induced acute kidney injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Nao-Ling-Su Capsule (NLSC) is a traditional prescription, which is composed of fifteen herbs such as epimedium, Polygala tenuifolia, and Schisandra chinensis. It has the effect of strengthening the brain, calming nerves, and protecting the kidney, which has been used clinically for many years to strengthen the brain and kidney. However, the effect of NLSC in the treatment of acute kidney injury (AKI) is still unclear. AIM OF THE STUDY: The present study aims to elucidate the pharmacological actions of NLSC in the treatment of AKI. MATERIALS AND METHODS: Molecular targets for NLSC and AKI were obtained from various databases, and then we built networks of interactions between proteins (PPI) by employing string databases. Additionally, we employed the DAVID database to conduct gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was conducted to analyze the interaction between core components and their corresponding core targets. Next, the C57BL male mice model of ischemia/reperfusion damage (IRI) was developed, and the nephridial protective effect of NLSC was evaluated. The accuracy of the expected targets was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR). The renal protective effect of NLSC was assessed using an immortalized human kidney tubular (HK-2) cell culture produced by oxygen-glucose deprivation (OGD). RESULTS: Network pharmacology analysis identified 199 common targets from NLSC and AKI. STAT3, HSP90AA1, TP53, MAPK3, JUN, JAK2, and VEGFA could serve as potential drug targets and were associated with JAK2/STAT3 signaling pathway, PI3K-Akt signaling pathway, etc. The molecular docking analysis confirmed significant docking activity between the main bioactive components and core targets, including STAT3 and KIM-1. Moreover, the AKI mice model was successfully established and NLSC pretreatment could improve renal function and alleviate renal damage. NLSC could alleviate renal inflammation and tubular cell apoptosis, and decrease the expression of STAT3 and KIM-1 in AKI mice. In vitro, both NLSC and drug-containing serum may protect HK-2 cells by inhibiting STAT3 signaling, especially STAT3-mediated apoptosis and KIM-1 expression. CONCLUSION: NLSC could alleviate renal inflammation and apoptosis, exerting its beneficial effects by targeting the STAT3/KIM-1 pathway. NLSC is a promising candidate for AKI treatment and provides a new idea and method for the treatment of AKI.

An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9 mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.

Unravelling the resilience of magnetite assisted granules to starvation and oxytetracycline stress.

Starvation and antibiotics pollution are two frequent perturbations during breeding wastewater treatment process. Supplying magnetite into anaerobic system has been proved efficient to accelerate microbial aggregates and alleviate the adverse effect caused by process disturbance. Nevertheless, whether these magnetite-based granules are still superior over normal granules after a long-term starvation period remains unknown, the responsiveness of these granules to antibiotics stress is also ambiguous. In current study, we investigated the resilience of magnetite-based anaerobic granular sludge (AnGS) to starvation and oxytetracycline (OTC) stress, by unravelling the variations of reactor performance, sludge properties, ARGs dissemination and microbial community. Compared with the AnGS formed without magnetite, the magnetite assisted AnGS appeared more robust defense to starvation and OTC stress. With magnetite supplement, the average methane yield after starvation recovery, 50 mg/L and 200 mg/L OTC stress was enhanced by 48.95%, 115.87% and 488.41%, respectively, accompanied with less VFAs accumulation, improved tetracycline removal rate (76.3-86.6% vs. 51.0-53.5%) and higher ARGs reduction. Meanwhile, magnetite supplement effectively ameliorated the potential sludge breakage by triggering more large granules formation. Trichococcus was considered an important impetus in maintaining the stability of magnetite-based AnGS process. By inducing more syntrophic methanogenesis partnerships, especially for hydrogenotrophic methanogenesis, magnetite ensured the improved reactor performance and stronger resilience at stress conditions.

Insights from the Endophytic Fungi in Amphisphaeria (Sordariomycetes): A. orixae sp. nov. from Orixa japonica and Its Secondary Metabolites.

Endophytic fungi are a remarkably diverse group of microorganisms that have imperceptible associations with their hosts for at least a part of their life cycle. The enormous biological diversity and the capability of producing bioactive secondary metabolites such as alkaloids, terpenoids, and polyketides have attracted the attention of different scientific communities, resulting in numerous investigations on these fungal endophytes. During our surveys of plant-root-based fungi in the mountain areas of Qingzhen, Guizhou Province, several isolates of endophytic fungi were identified. In this study, a novel endophytic fungus was discovered in the roots of a medicinal plant (Orixa japonica) in Southern China and introduced as a new species (Amphisphaeria orixae) based on morphological evidence and molecular phylogenetic analysis (combined ITS and LSU sequence data). To the best of our knowledge, A. orixae is the first reported endophyte as well as the first hyphomycetous asexual morph in Amphisphaeria. A new isocoumarin, (R)-4,6,8-trihydroxy-5-methylisochroman-1-one (1), and 12 known compounds (2-13) were isolated from the rice fermentation products of this fungus. Using 1D- and 2D-NMR, mass spectrometry, and ECD studies, their structures were identified. The antitumor activity of these compounds was tested. Unfortunately, none of the compounds tested showed significant antitumor activity.

Curcumin inhibits proliferation of hepatocellular carcinoma cells by blocking PTPN1 and PTPN11 expression.

The antitumor mechanism of curcumin is unclear, especially in hepatocellular carcinoma (HCC) cells. To clarify the mechanism of action of curcumin in the effective treatment of HCC, the targets of curcumin were screened and validated. Candidate genes of curcumin for HCC were screened using the traditional Chinese medicine systems pharmacology (TCMSP) database and validated using The Cancer Genome Atlas (TCGA) database. The correlation of mRNA expression levels between key candidate genes was identified in the TCGA liver hepatocellular carcinoma (LIHC) dataset. The effects on prognosis were analyzed to identify the target gene of curcumin, which inhibits HCC cell proliferation. Based on the subcutaneous xenograft model of human HCC in nude mice, the expression levels of target proteins were observed using immunohistochemistry. The analysis results of the present study identified the target genes of curcumin, which were obtained by screening the TCSMP database. The protein tyrosine phosphatase non-receptor type 1 (PTPN1) was obtained from TCGA database analysis of the targeted genes. The expression levels of PTPN1 and its homologous sequence genes in TCGA LIHC project was analyzed to identify the potential target gene of curcumin, for use in HCC treatment. Next, xenograft experiments were performed to investigate the therapeutic effects of curcumin in an animal model. Curcumin was demonstrated to inhibit the growth of HCC xenograft tumors in mice. Immunohistochemistry results demonstrated that the protein expression levels of PTPN1 and PTPN11 in the curcumin group were significantly lower compared with those in the control group. In conclusion, these results demonstrated that curcumin inhibits the proliferation of HCC cells by inhibiting the expression of PTPN1 and PTPN11.

Metal coordination micelles for anti-cancer treatment by gene-editing and phototherapy.

CRISPR-Cas9 is a central focus of the emerging field of gene editing and photodynamic therapy (PDT) is a clinical-stage ablation modality combining photosensitizers with light irradiation. But metal coordination biomaterials for the applications of both have rarely been investigated. Herein, Chlorin-e6 (Ce6) Manganese (Mn) coordination micelles loaded with Cas9, termed Ce6-Mn-Cas9, were developed for augmented combination anti-cancer treatment. Manganese played multiple roles to facilitate Cas9 and single guide RNA (sgRNA) ribonucleoprotein (RNP) delivery, Fenton-like effect, and enhanced endonuclease activity of RNP. Histidine (His)-tagged RNP could be coordinated to Ce6 encapsulated in Pluronic F127 (F127) micelles by simple admixture. Triggered by ATP and endolysosomal acidic pH, Ce6-Mn-Cas9 released Cas9 without altering protein structure or function. Dual guide RNAs were designed to target the antioxidant regulator MTH1 and the DNA repair protein APE1, resulting in increased oxygen and enhanced PDT effect. In a murine tumor model, Ce6-Mn-Cas9 inhibited tumor growth with the combination therapy of PDT and gene editing. Taken together, Ce6-Mn-Cas9 represents a new biomaterial with a high degree of versatility to enable photo- and gene-therapy approaches.

Biodegradable Sodium Alginate/Carrageenan/Cellulose Composite Hydrogel Wound Dressings Containing Herbal Extracts for Promoting Blood Coagulation and Wound Healing.

Accelerating the coagulation process and preventing wound infection are major challenges in the wound care process. Therefore, new multifunctional wound dressings with procoagulant, antibacterial, and antioxidant properties have enormous potential for clinical application. In this work, biodegradable hydrogels containing herbal extracts are prepared for wound dressings. First, the active ingredients are extracted from Amaranthus spinosus (A. spinosus) and Rubia cordifolia (R. cordifolia) and added to the hydrogels prepared from microcrystalline cellulose (MCC), carrageenan, and sodium alginate. Then the composite hydrogels are air-dried to obtain the wound dressings. The wound dressings prepared in this work have good biocompatibility and moisture retention. The mechanical properties of the wound dressings are further improved with the addition of MCC. Besides, the wound dressings have excellent procoagulant, antibacterial, and antioxidant properties due to the presence of R. cordifolia extract. Overall, the most effective group of wound dressings with different ingredient formulations reduces clotting time by 75% and largely inhibits bacterial growth. The wound dressings perform well in the animal wound models to promote wound healing. These results indicate that the hydrogel wound dressings prepared in this work have great potential for medical applications.

MRI diagnose post-operative anastomotic leak in patients with rectal cancer: preliminary experience.

BACKGROUND: Anastomotic leakage (AL) is one of the most serious postoperative complications after colorectal anastomosis. This study aims to evaluate the feasibility and diagnostic accuracy of magnetic resonance imaging (MRI) in the early detection of AL in patients with clinically suspected AL after rectal anterior resection. METHODS: This was a prospective study including patients who underwent anterior resection and postoperative MRI examination. AL was diagnosed by comprehensive indictors, which were mainly confirmed by clinical signs, symptoms, and retrograde contrast enema (RCE) radiography. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of diagnosing AL with MRI were calculated. RESULTS: In total, 347 patients received anterior resection for rectal cancer, and 28 patients were suspected to have AL. Finally, 23 patients were included and received MRI examination. The median time interval from surgery to MRI was 10 days (3-21 days). The median distance from anastomosis to anal verge was 4.0 cm (2.0-10 cm), and 11 patients underwent diverted ileostomy. Eighteen patients had an anastomotic leak, including one patient who had a pelvic abscess and five patients who had no evidence of AL in the MRI examination. The overall sensitivity and specificity were 94.4% (95% CI 70.6% to 99.7%) and 80% (95% CI 29.8% to 98.9%), respectively. The PPV was 0.94 (95% CI 0.71 to 0.99) and the NPV was 0.80 (95% CI 0.29 to 0.99). For patients who had anastomosis less than 5 cm, the diagnostic accuracy of MRI was 93.7% (15/16). T2-weighted imaging with fat suppression can effectively reveal the leak track. CONCLUSIONS: The accuracy of plain MRI examination in diagnosing AL was favorable for patients with a suspected AL. T2-weighted imaging with fat suppression was the best imaging modality to diagnose AL. A multicenter prospective study with more samples is needed to further determine the safety and feasibility of MRI in the diagnosis of AL.

Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer.

BACKGROUND: Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. METHODS: We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. RESULTS: Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. CONCLUSION: This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring.

Habitual fish oil supplementation and the risk of incident atrial fibrillation: findings from a large prospective longitudinal cohort study.

AIMS: Mixed effects of fish oil supplementation on the risks of atrial fibrillation (AF) were observed in several large-scale randomized controlled trials. Whether this relationship would be modified by genetic AF risk, baseline cardiovascular disease (CVD) status and background oily fish consumption are unknown. METHODS AND RESULTS: We included 468 665 participants without AF at baseline from the UK Biobank cohort. The association between fish oil supplementation and the AF risk was assessed in the study cohort and in several subgroups, including genetic AF predisposition, baseline CVD status, and background oily fish consumption. During a median follow-up of 11.1 years, fish oil users had a higher rate of incident AF (6.2% vs. 5.2%, adjusted hazard ratio of 1.10, and 95% confidence interval of 1.07, 1.13). Compared with non-users, fish oil users had a higher rate of incident AF in the low (3.7% vs. 3.0%, P= 0.02), intermediate (5.8% vs. 4.8%, P < 0.0001), and high (9.8% vs. 8.1%, P < 0.0001) genetic AF risk groups. In participants without CVD at baseline, fish oil users had a higher rate of incident AF (5.3% vs. 4.1%, P < 0.0001), which was not observed in participants with CVD at baseline (11.6% vs. 11.1%, P = 0.56), with significant interaction (P-interaction < 0.0001). The association between fish oil supplementation and the AF risk was not modified by background oily fish consumption (P-interaction = 0.62). CONCLUSION: Habitual fish oil supplementation was associated with the risk of incident AF, regardless of genetic AF predisposition and background oily fish consumption. This association was observed only in individuals without CVD at baseline.

[Preparation of salvianolic acid B, tanshinone â ¡_A, and glycyrrhetinic acid lipid emulsion and its protective effect against acute liver injury induced by acetaminophen].

Salvianolic acid B(Sal B), tanshinone Ⅱ_A(TSN Ⅱ_A), and glycyrrhetinic acid(GA) lipid emulsion(GTS-LE) was prepared by the high-speed dispersion method combined with ultrasonic emulsification.The preparation process of the emulsion was optimized by single-factor method and D-optimal method with appearance, centrifugal stability, and particle size of the emulsion as evalua-tion indexes, followed by verification.In vitro release of Sal B, TSN Ⅱ_A, and GA in GTS-LE was performed by reverse dialysis.In vivo pharmacokinetic evaluation was carried out in mice.The acute liver injury model was induced by acetaminophen.The effect of oral GTS-LE on the acute liver injury was investigated by serum liver function indexes and pathological changes in liver tissues of mice.The results showed that under the optimal preparation process, the average particle size of GTS-LE was(145.4±9.25) nm and the Zeta potential was(-33.6±1.45) mV.The drug-loading efficiencies of Sal B, TSN Ⅱ_A, and GA in GTS-LE were above 95%, and the drug release in vitro conformed to the Higuchi equation.The pharmacokinetic results showed that the C_(max) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.128, 2.7, and 2.85 times that of the GTS-S group, and AUC_(0-t) of Sal B, TSN Ⅱ_A, and GA in GTS-LE was 3.09, 2.23, and 1.9 times that of the GTS-S group.After intragastric administration of GTS-LE, the activities of alanine aminotransferase and aspartate aminotransferase were significantly inhibited, the content of malondialdehyde was reduced, and the structure of hepatocytes recovered to normal.In conclusion, GTS-LE can delay the release of Sal B and promote the release of TSN Ⅱ_A and GA.The encapsulation of three drug components in the emulsion can improve the oral bioavailability to varying degrees and can effectively prevent the acute liver injury caused by acetaminophen.

[Preparation of tanshinone â ¡_A-glycyrrhetinic acid solid lipid nanoparticles and its inhibitory effect on acne].

The optimal prescription of tanshinone Ⅱ_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.

Triage Nurse-Activated Emergency Evaluation Reduced Door-to-Needle Time in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

Methods: This was a retrospective analysis in a general hospital emergency department in Beijing, China. 212 adult AIS patients treated with thrombolysis who failed to use EMSs were included. In addition to DNT, door-to-vein open time (DVT), door-to-blood sample deliver time (DBT), and 7-day NIHSS scores were evaluated. Results: 137 (64.6%) patients were in the triage nurse-activated group and 75 (35.4%) patients were in the doctor-activated group. The DNT of the triage nurse-activated group was significantly reduced compared with the doctor-activated group (28 (26, 32.5) min vs. 30 (28, 40) min, p=0.001). DNT less than 45 min was seen in 95.6% of patients in the triage nurse-activated group and 84% of patients in the doctor-activated group (p=0.011, OR 3.972, 95% CI 1.375-11.477). In addition, DVT (7 (4, 10) min vs. 8 (5, 12) min, P=0.025) and DBT (15 (13, 21) min vs. 19 (15, 26) min, p=0.001) of the triage nurse-activated group were also shorter than those of the doctor-activated group (p < 0.05). The 7-day NIHSS scores were not statistically different between the two groups. Conclusions: Triage nurse-activated urgent emergency evaluation could reduce the door-to-needle time, which provides a feasible opportunity to optimize the emergency department service for AIS patients who failed to use emergency medical services.

Surfactant-Stripped Semiconducting Polymer Micelles for Tumor Theranostics and Deep Tissue Imaging in the NIR-II Window.

Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.

Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis.

BACKGROUND: Hepatocellular carcinoma is insensitive to many chemotherapeutic agents. Ferroptosis is a form of programmed cell death with a Fenton reaction mechanism. It converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals, which inhibit hepatocellular carcinoma progression. METHODS: The morphology, elemental composition, and tumour microenvironment responses of various organic/inorganic nanoplatforms were characterised by different analytical methods. Their in vivo and in vitro tumour-targeting efficacy and imaging capability were analysed by magnetic resonance imaging. Confocal microscopy, flow cytometry, and western blotting were used to investigate the therapeutic efficacy and mechanisms of complementary ferroptosis/apoptosis mediated by the nanoplatforms. RESULTS: The nanoplatform consisted of a silica shell doped with iron and disulphide bonds and an etched core loaded with doxorubicin that generates hydrogen peroxide in situ and enhances ferroptosis. It relied upon transferrin for targeted drug delivery and could be activated by the tumour microenvironment. Glutathione-responsive biodegradability could operate synergistically with the therapeutic interaction between doxorubicin and iron and induce tumour cell death through complementary ferroptosis and apoptosis. The nanoplatform also has a superparamagnetic framework that could serve to guide and monitor treatment under T2-weighted magnetic resonance imaging. CONCLUSION: This rationally designed nanoplatform is expected to integrate cancer diagnosis, treatment, and monitoring and provide a novel clinical antitumour therapeutic strategy.

[A novel PPG pulse diagnosis instrument which can be used to assist the application of acupuncture and moxibustion].

For a long time, Chinese medicine has attached great importance to "pulse diagnosis for patients before acupuncture treatment", which emphasizes the close relationship between pulse diagnosis and acupuncture. Pulse diagnosis information is closely related to acupuncture research and runs through the whole process of diagnosis and treatment. However, the lack of repeatable and quantifiable real-time detection means of pulse diagnosis information has affected the application of pulse diagnosis in acupuncture research. Photo plethysmo graphy (PPG) technology has the advantages of convenient acquisition, low price, non-invasive, easy to use and so on. Under the guidance of TCM diagnosis theory, this paper discussed the principle and characteristics of fingertip volumetric pulse wave, studied its relationship with Cunkou pulse diagnosis, developed a new fingertip blood volumetric pulse wave measuring instrument, explored the acquisition and measurement methods of volumetric pulse wave signal, and proposed the relationship between the measuring instrument and acupuncture research. It can provide basic tools and data analysis and support for acupuncture research.

AnnexinA5 Might Suppress the Phenotype of Human Gastric Cancer Cells via ERK Pathway.

Gastric cancer is one of the most fatal diseases around the world. However, the mechanism of the development of gastric cancer is still not clarified. In addition, the anticancer drugs have cytotoxicity with different degrees. AnnexinA5, a member of the annexin family, has a great binding ability with the membrane phospholipid in a calcium dependent manner and is involved in the development of various cancers. This study aims to explore the influence of annexinA5 on human gastric cancer cells and whether it has the potential to be an auxiliary treatment to gastric cancer. In this study, the role of annexinA5 was detected from both the endogenous and the exogenous aspects on the gastric cancer cell lines MGC-803 and MKN-45. The cells were divided into a knockdown group in which RNA interference technique was used to suppress annexinA5 expression and a protein-supplementing group in which annexinA5 protein was added in the culture supernatant. After the suppression ratio of RNA interference was determined and the IC50 of annexinA5 protein was decided respectively, the cells' proliferation was detected by MTT assay, colony formation assay, and the expression of PCNA. FCM assay and PI staining methods were applied to test cell apoptosis and necrosis. To investigate whether ANXA5 influence cell metastasis, wound healing assay and transwell assay were employed. To further detect the mechanism of annexinA5 action, the signal pathway was examined with Western Blot method. When ANXA5 gene was knocked down, cell proliferation and metastasis were promoted, while cell apoptosis was suppressed. On the other hand, after the annexinA5 protein was applied to the gastric cancer cells, cell proliferation and metastasis were inhibited, while cell apoptosis and necrosis were promoted. AnnexinA5 played its role via ERK signal pathway. ANXA5 acted as tumor suppressor gene in the gastric cancer by suppressing ERK signal pathway and has the potentiality to be an auxiliary anticancer agent.

Diagnostic analysis of new quantitative parameters of low-dose dynamic myocardial perfusion imaging with CZT SPECT in the detection of suspected or known coronary artery disease.

The goal of this study is to explore and evaluate the diagnostic values of myocardial blood flow (MBF), myocardial flow reserve (MFR) and relative flow reserve (RFR) obtained with low-dose dynamic CZT SPECT for patients with suspected or known coronary artery disease (CAD). Fifty-seven consecutive patients who underwent low-dose dynamic CZT SPECT and CAG were enrolled. MBF, MFR and RFR were calculated on the vessel level with dedicated quantitative software, and the difference and correlation of each parameter was compared according to the reference standard of stenosis ≥ 50% or ≥ 75% on CAG, respectively. ROC curves were made by stress MBF (sMBF), rest MBF (rMBF), MFR and RFR. The optimal cut-off values and corresponding diagnostic efficacy were obtained and compared with each other. Results indicated that when stenosis ≥ 50% or ≥ 75% on CAG was used as the reference standard at the vessel level, there was no statistically significant difference in rMBF between the negative group and the positive group (P > 0.05), and the sMBF and MFR in positive groups were significantly lower than that in the negative group (all P < 0.05). There was a moderate to significant correlation between sMBF and MFR, sMBF and RFR, MFR and RFR (all P < 0.0001). These results indicate that low-dose dynamic CZT SPECT imaging can easily obtain the sMBF, MFR and RFR, and there is a good correlation among the three parameters, which has a certain diagnostic value for patients with suspected or known CAD, and is a useful supplement to the conventional qualitative or semi-quantitative diagnostic methods.

Prognostic significance of lymph node yield in patients with synchronous colorectal carcinomas.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines recommend examination of a minimum of 12 lymph nodes (LNs) for accurate staging of a single case of colorectal cancer. However, the guidelines do not support the examination of LNs in synchronous colorectal carcinoma (SCC). This study aimed to investigate the association between lymph node yield and the prognosis of SCC patients. METHODS: Synchronous colorectal carcinoma patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database over a 10-year interval (2004 to 2013). Systematic dichotomization for optimal cut-off point identification was performed using X-tile. The baseline for the two LNs groups generated was balanced using the propensity score matching (PSM) method. RESULTS: A total of 4616 patients met the inclusion criteria. The cut-off number for lymph node retrieved from a single patient was 15 and 12 for the first- and second-time diagnosis of SCC, respectively. Age, T category, N category, tumor grade, tumor site, tumor size, and radiation sequence were not balanced in the two groups. After adjusting the baseline in the two groups, the same results were observed. Age, T category, N category, tumor site had a partial effect on lymph node yield. There might be some biological characteristics of the tumor that influence lymph node yield. CONCLUSIONS: Retrieval of fewer than 15 LNs at the first time of SCC diagnosis indicates worse SCC prognosis. Because factors such as manner of surgical examination influence SCC prognosis, specimens should be preserved for at least 6 months to enable reevaluation should there be a need. Irb: IRB approval is not required because the SEER data are freely accessible.