Technical note: A small animal irradiation platform for investigating the dependence of the FLASH effect on electron beam parameters.

BACKGROUND: The recent rediscovery of the FLASH effect, a normal tissue sparing phenomenon observed in ultra-high dose rate (UHDR) irradiations, has instigated a surge of research endeavors aiming to close the gap between experimental observation and clinical treatment. However, the dependences of the FLASH effect and its underpinning mechanisms on beam parameters are not well known, and large-scale in vivo studies using murine models of human cancer are needed for these investigations. PURPOSE: To commission a high-throughput, variable dose rate platform providing uniform electron fields (≥15 cm diameter) at conventional (CONV) and UHDRs for in vivo investigations of the FLASH effect and its dependences on pulsed electron beam parameters. METHODS: A murine whole-thoracic lung irradiation (WTLI) platform was constructed using a 1.3 cm thick Cerrobend collimator forming a 15 × 1.6 cm2 slit. Control of dose and dose rate were realized by adjusting the number of monitor units and couch vertical position, respectively. Achievable doses and dose rates were investigated using Gafchromic EBT-XD film at 1 cm depth in solid water and lung-density phantoms. Percent depth dose (PDD) and dose profiles at CONV and various UHDRs were also measured at depths from 0 to 2 cm. A radiation survey was performed to assess radioactivation of the Cerrobend collimator by the UHDR electron beam in comparison to a precision-machined copper alternative. RESULTS: This platform allows for the simultaneous thoracic irradiation of at least three mice. A linear relationship between dose and number of monitor units at a given UHDR was established to guide the selection of dose, and an inverse-square relationship between dose rate and source distance was established to guide the selection of dose rate between 20 and 120 Gy·s-1 . At depths of 0.5 to 1.5 cm, the depth range relevant to murine lung irradiation, measured PDDs varied within ±1.5%. Similar lateral dose profiles were observed at CONV and UHDRs with the dose penumbrae widening from 0.3 mm at 0 cm depth to 5.1 mm at 2.0 cm. The presence of lung-density plastic slabs had minimal effect on dose distributions as compared to measurements made with only solid water slabs. Instantaneous dose rate measurements of the activated copper collimator were up to two orders of magnitude higher than that of the Cerrobend collimator. CONCLUSIONS: A high-throughput, variable dose rate platform has been developed and commissioned for murine WTLI electron FLASH radiotherapy. The wide field of our UHDR-enabled linac allows for the simultaneous WTLI of at least three mice, and for the average dose rate to be modified by changing the source distance, without affecting dose distribution. The platform exhibits uniform, and comparable dose distributions at CONV and UHDRs up to 120 Gy·s-1 , owing to matched and flattened 16 MeV CONV and UHDR electron beams. Considering radioactivation and exposure to staff, Cerrobend collimators are recommended above copper alternatives for electron FLASH research. This platform enables high-throughput animal irradiation, which is preferred for experiments using a large number of animals, which are required to effectively determine UHDR treatment efficacies.

Organic-inorganic covalent-ionic molecules for elastic ceramic plastic.

Although organic-inorganic hybrid materials have played indispensable roles as mechanical1-4, optical5,6, electronic7,8 and biomedical materials9-11, isolated organic-inorganic hybrid molecules (at present limited to covalent compounds12,13) are seldom used to prepare hybrid materials, owing to the distinct behaviours of organic covalent bonds14 and inorganic ionic bonds15 in molecular construction. Here we integrate typical covalent and ionic bonds within one molecule to create an organic-inorganic hybrid molecule, which can be used for bottom-up syntheses of hybrid materials. A combination of the organic covalent thioctic acid (TA) and the inorganic ionic calcium carbonate oligomer (CCO) through an acid-base reaction provides a TA-CCO hybrid molecule with the representative molecular formula TA2Ca(CaCO3)2. Its dual reactivity involving copolymerization of the organic TA segment and inorganic CCO segment generates the respective covalent and ionic networks. The two networks are interconnected through TA-CCO complexes to form a covalent-ionic bicontinuous structure within the resulting hybrid material, poly(TA-CCO), which unifies paradoxical mechanical properties. The reversible binding of Ca2+-CO32- bonds in the ionic network and S-S bonds in the covalent network ensures material reprocessability with plastic-like mouldability while preserving thermal stability. The coexistence of ceramic-like, rubber-like and plastic-like behaviours within poly(TA-CCO) goes beyond current classifications of materials to generate an 'elastic ceramic plastic'. The bottom-up creation of organic-inorganic hybrid molecules provides a feasible pathway for the molecular engineering of hybrid materials, thereby supplementing the classical methodology used for the manufacture of organic-inorganic hybrid materials.

Evolutionary Adaptation of Genes Involved in Galactose Derivatives Metabolism in Oil-Tea Specialized Andrena Species.

Oil-tea (Camellia oleifera) is a woody oil crop whose nectar includes galactose derivatives that are toxic to honey bees. Interestingly, some mining bees of the genus Andrena can entirely live on the nectar (and pollen) of oil-tea and are able to metabolize these galactose derivatives. We present the first next-generation genomes for five and one Andrena species that are, respectively, specialized and non-specialized oil-tea pollinators and, combining these with the published genomes of six other Andrena species which did not visit oil-tea, we performed molecular evolution analyses on the genes involved in the metabolizing of galactose derivatives. The six genes (NAGA, NAGA-like, galM, galK, galT, and galE) involved in galactose derivatives metabolism were identified in the five oil-tea specialized species, but only five (with the exception of NAGA-like) were discovered in the other Andrena species. Molecular evolution analyses revealed that NAGA-like, galK, and galT in oil-tea specialized species appeared under positive selection. RNASeq analyses showed that NAGA-like, galK, and galT were significantly up-regulated in the specialized pollinator Andrena camellia compared to the non-specialized pollinator Andrena chekiangensis. Our study demonstrated that the genes NAGA-like, galK, and galT have played an important role in the evolutionary adaptation of the oil-tea specialized Andrena species.

Quantification of Cardiomyocyte Contraction In Vitro and Drug Screening by MyocytoBeats.

Cardiomyocyte contractility is the crucial feature of heart function. Quantifying cardiomyocyte contraction in vitro is essential for disease phenotype characterization, mechanism illumination, and drug screening. Although many experimental methods have been employed to determine contraction dynamics in vitro, a time-saving and easy-to-use software is still needed to be developed. We presented a reliable tool, named MyocytoBeats, to measure cardiomyocyte contraction by processing recorded videos. Analysis results by MyocytoBeats of various experimental models have shown a significant linear relationship with another validated software. We also performed pharmacology screen in the platform, and astragaloside IV was identified to stabilize the frequency and amplitude of cardiomyocyte in the arrhythmia model. MyocytoBeats is a high-performance tool for generating cardiomyocyte contraction data of vitro study and shows a great potential in cardiac pharmacology study.

Zero-Valence Selenium-Enriched Prussian Blue Nanozymes Reconstruct Intestinal Barrier against Inflammatory Bowel Disease via Inhibiting Ferroptosis and T Cells Differentiation.

The structural disruption of mechanical barrier and dysfunction of immune barrier in intestinal, are important factors, that aggravate inflammatory bowel disease (IBD). To tackle this challenge, a multifunctional nanozyme capable of scavenging reactive oxygen species (ROS) and inhibiting ferroptosis or T cells differentiation for IBD therapy is here reported. In this work, zero-valence selenium-enriched Prussian blue nanozymes (Se-HMPB nanozymes) are prepared via the hard template method. PB nanozymes with multi-enzyme activities can effectively scavenge various ROS in inflammatory tissues. Meanwhile, the presence of selenium element endows the glutathione peroxidase activity of Se-HMPB nanozymes, which can inhibit ferroptosis and reverse the lipid peroxidation of intestinal epithelial cells to protect the intestinal mechanical barrier in ulcerative colitis (UC) model. In addition, selenium supplementation can realize efficient inhibition on the differentiation of T cells in Crohn's disease (CD) model, regulating the intestinal immune barrier. Thus, the Se-HMPB nanozymes reconstructed intestinal barrier via inhibiting ferroptosis and T cells differentiation in UC and CD models, depicting great potential to alleviate IBD.

Enhancing low-temperature thermal remediation of petroleum sludge by solvent deasphalting.

Thermal treatment is a promising technique for treating petroleum sludge (PS). However, asphaltenes as a recalcitrant fraction of PS induce strong bounding between petroleum and minerals, and therefore lead to the need for high temperature and hence high energy consumption in thermal treatment of PS. In this study, a novel method combining a deasphalting pretreatment of PS with low-temperature thermal desorption (LTTD) was developed. The efficiency of deasphalting was found to be positively correlated to the ability of n-alkanes and asphaltene dispersants in dispersing asphaltenes. In treating six different kinds of PS, the residual oil contents were all below 2.5% after the deasphalting alone. Compared with direct thermal desorption at 600 °C for 1 h, dodecyl benzene sulfonic acid (DBSA)-assisted heptane deasphalting made thermal desorption at 350 °C for 1 h sufficient to treat these APS. The residual oil content of sludge after LTTD is lower than 0.45%. FT-IR, Raman spectra and XPS analysis confirmed that the carbon residue in APS after LTTD is primarily graphite state, which is extremely stable and does not migrate to the surrounding environment as compared with the crude oil in the APS. Hence, solvent deasphalting results in effective treatment of PS by LTTD, while the solvent can be recycled by distillation and crude oil recovered as value-added petroleum resource. The LTTD represents therefore a novel green strategy for treating PS and resource utilization.

New paeonol derivative C302 reduces hypertension in spontaneously hypertensive rats through endothelium-dependent and endothelium-independent vasodilation.

Hypertension is a major risk factor for cardiovascular disease and Chinese herb monomers could provide new structural skeletons for anti-hypertension new drug development. Paeonol is a Chinese herbal monomer extracted from Cortex moutan, exhibited some anti-hypertensive activity. The study focused on the structural optimization of paeonol to provide promising lead compounds for anti-hypertension new drug development. Herein, twelve new paeonol derivatives (PD) were designed and synthesized and their vasodilation activity was evaluated by in vitro vasodilation drug screening platform based on Myograph. Its anti-hypertension activity, PD-C302 (2-hydroxy-4-methoxyvalerophenone) as a representative with the optimal vasodilation activity, was determined by its response to blood pressure in spontaneously hypertensive rats (SHR) in vivo. Moreover, its molecular mechanism was probed by the vasodilation activity of rat superior mesenteric artery rings with or without endothelium pre-contracted by potassium chloride (KCl) or phenylephrine hydrochloride (PE). It was indicated that PD-C302 significantly reduced the blood pressure in SHR, which would involve in PD-C302-induced vasodilation. Furthermore, endothelium-dependent pathways and endothelium-independent pathways both contributed importantly to PD-C302-induced vasodilation at low concentration of PD-C302. Endothelium-independent pathways (vascular smooth muscle cell-mediated vasodilation), were mainly responsible for the PD-C302-induced vasodilation at high concentration of PD-C302, which involved in opening multiple K+ channels to restrain Ca2+ channels, and then triggered vasodilation to reduce blood pressure. PD-C302 has a simple structure and favorable anti-hypertensive activity in vivo, which could be a promising lead compound for anti-hypertension new drug development.

Bear bile powder attenuates senecionine-induced hepatic sinusoidal obstruction syndrome in mice.

Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.

Programmed Stimuli-Responsive Carbon Dot-Nanogel Hybrids for Imaging-Guided Enhanced Tumor Phototherapy.

For harmonizing the contradiction of nanotheranostic agents between enhanced tumor accumulation and penetration, efficient cell internalization and fast elimination are key tactics for promoting their clinical applications. Herein, programmed stimuli-responsive poly(N-isopropylacrylamide)-carbon dot (PNIPAM-CD) hybrid nanogels are designed to address the abovementioned conflicts. The enlarged particle size of PNIPAM-CDs enables one to effectively improve their accumulation at tumor sites. Once the hybrid nanogels are docked in tumors and exposed to deep-red-light (660 nm) irradiation, heat and reactive oxygen species (ROS) are generated from the CDs, consequently activating photothermal therapy (PTT) and photodynamic therapy (PDT) effects and meanwhile inducing partial degradation of PNIPAM-CDs for deep tissue penetration. Further, enhanced cellular internalization of the functional components can be achieved owing to the pH-responsive charge reversal and temperature-dependent hydrophilic/hydrophobic conversion characteristics of PNIPAM-CDs. Finally, the overexpressed glutathione (GSH) in tumor cells would trigger further cleavage of the partially degraded hybrid nanogels, which is beneficial for their rapid clearance from the body. This work not only proposed a novel strategy to fabricate nanotheranostic agents using just a single functional component (i.e., the versatile CDs) to simplify the preparation process but also achieved effective delivery of agents into tumor cells by overcoming the multiple biological barriers to enhance therapeutic efficacy and decrease side effects.

[Mechanism of Gynostemma pentaphyllum in treatment of metabolism associated fatty liver disease based on network pharmacology and molecular docking].

The present study explored the mechanism of action of Gynostemma pentaphyllum in the treatment of metabolism associa-ted fatty liver disease(MAFLD) by network pharmacology and molecular docking. The main active components and action targets of G. pentaphyllum were collected from TCMSP. Disease-related targets were obtained from GeneCards, OMIM and TTD, and the common targets of the three databases were screened out, which were converted to the genes with standard names by UniProt. The drug-disease common target genes were obtained through Venn tool and uploaded to STRING for the construction of the protein-protein interaction(PPI) network. Cytoscape was used to construct and analyze the drug-active component-common target-disease network. The gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed on the common targets by DAVID. Pymol was adopted to perform molecular docking of active components and the common targets and predict their binding ability. Twenty-four active components(such as gypenosides, quercetin and sitosterol) of G. pentaphyllum were screened out. Ninety-two targets were obtained and 54 common targets were identified. Key targets included TNF, IL6, PTGS2, TP53, CCL2 and VEGFA. GO analysis on biological processes, molecular functions and cellular components and KEGG pathway analysis were performed, and the results indicated that NF-κB, PI3 K-Akt, TNF and HIF-1 signaling pathways were mainly involved. Molecular docking results showed that gypenosides and quercetin had a strong binding ability to TNF, IL6 and PTGS2. The findings of this study revealed that the therapeutic efficacy of G. pentaphyllum on MAFLD might be achieved by resisting inflammation and oxidative stress and improving insulin resistance, providing ideas and a theoretical basis for the development and application of G. pentaphyllum in the treatment of MAFLD.

Root Endophytic Fungal Community and Carbon and Nitrogen Stable Isotope Patterns Differ among Bletilla Species (Orchidaceae).

Orchids of the genus Bletilla are well-known ornamental plants and sources of traditional medicine in Asia that rely on the symbiotic relationship with root endophytic fungi throughout their whole life cycle. However, little is known about their fungal partners, infection pattern, and pathways of carbon gain. We investigated carbon and nitrogen stable isotope patterns in different organs of three Bletilla species, identified the root endophytic fungal community composition, and determined mycorrhizal colonization rates. The three Bletilla species were comprised by a polyphyletic group which belongs to different trophic modes, such as saprotroph, pathotroph, and symbiotroph; however, the dominant species and their abundances varied among Bletilla spp. Mycorrhizal infection rates also varied among Bletilla species, with B. striata (65% ± 25%) being significantly higher than those of B. formosana (35% ± 16%) and B. ochracea (22% ± 13%). Compared with surrounding autotrophic plants, all Bletilla spp. were significantly enriched in 13C with B. striata to a significantly higher level than other two Bletilla species. Among different organs, stems had higher δ13C values, while leaves and flowers had higher δ15N and total N content values across all three species. Our results indicate that the symbiotic relationship of Bletilla and its root endophytic fungi is not strictly specific. Although mycorrhizal infection rates were highly variable, the three Bletilla species had the same infection pattern with hyphae penetrating the cortex cell by the pathway cell. Different Bletilla species have different strategies for C allocation among plant organs. These findings provide new insights into the ecological adaptation of orchids and will contribute to Bletilla germplasm conservation and sustainable utilization.

Photothermally triggered nitric oxide nanogenerator targeting type IV pili for precise therapy of bacterial infections.

Nitric oxide (NO) is an important biological messenger involved in the treatment of bacterial infections, but its controlled and targeted release in bacterial infections remains a major challenge. Herein, an intelligent NO nanogenerator triggered by near-infrared (NIR) light is constructed for targeted treatment of P. aeruginosa bacterial infection. Since maleimide can recognize and attach to the pilus of T4P of P. aeruginosa, we adopt this strategy to achieve the accurate release of therapeutic drugs at the infection site, i.e., after maleimide targets Gram-negative bacteria, the SNP@MOF@Au-Mal nanogenerator will release NO and generate ROS in situ from the inorganic photosensitizer gold nanoparticles under NIR irradiation to achieve synergistic antibacterial effect. In vivo experiments proved that the bacterial burden on the wound was reduced by 97.7%. Additionally, the nanogenerator was shown to promote the secretion of growth factors, which play a key role in regulating inflammation and inducing angiogenesis. This strategy has the advantage of generating a high concentration of NO in situ to promote the transfer of more NO and its derivatives (N2O3, ONOO-) to bacteria, thereby significantly improving the antibacterial effect. The multifunctional antibacterial platform has been demonstrated as a good carrier for gas therapy because of its simple and efficient gas release performance, indicating its great potential for the treatment of drug-resistant bacterial infections.

Mechanism of Gynostemma pentaphyllum in treatment of metabolism associated fatty liver disease based on network pharmacology and molecular docking / 中国中药杂志

The present study explored the mechanism of action of Gynostemma pentaphyllum in the treatment of metabolism associa-ted fatty liver disease(MAFLD) by network pharmacology and molecular docking. The main active components and action targets of G. pentaphyllum were collected from TCMSP. Disease-related targets were obtained from GeneCards, OMIM and TTD, and the common targets of the three databases were screened out, which were converted to the genes with standard names by UniProt. The drug-disease common target genes were obtained through Venn tool and uploaded to STRING for the construction of the protein-protein interaction(PPI) network. Cytoscape was used to construct and analyze the drug-active component-common target-disease network. The gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed on the common targets by DAVID. Pymol was adopted to perform molecular docking of active components and the common targets and predict their binding ability. Twenty-four active components(such as gypenosides, quercetin and sitosterol) of G. pentaphyllum were screened out. Ninety-two targets were obtained and 54 common targets were identified. Key targets included TNF, IL6, PTGS2, TP53, CCL2 and VEGFA. GO analysis on biological processes, molecular functions and cellular components and KEGG pathway analysis were performed, and the results indicated that NF-κB, PI3 K-Akt, TNF and HIF-1 signaling pathways were mainly involved. Molecular docking results showed that gypenosides and quercetin had a strong binding ability to TNF, IL6 and PTGS2. The findings of this study revealed that the therapeutic efficacy of G. pentaphyllum on MAFLD might be achieved by resisting inflammation and oxidative stress and improving insulin resistance, providing ideas and a theoretical basis for the development and application of G. pentaphyllum in the treatment of MAFLD.

Efficacy of a Chinese herbal formula on hepatitis B e antigen-positive chronic hepatitis B patients.

BACKGROUND: No guideline recommends antiviral therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus (HBV) DNA viral load. AIM: To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection. METHODS: In total, 395 patients (30-65 years old) with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk. Endpoints to evaluate therapeutic efficacy included: (1) HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96; and (2) HBeAg clearance and seroconversion rates at weeks 48 and 96. RESULTS: HBV DNA levels ≤ 4 log10 IU/mL were 10.05% at week 48 and 18.59% at week 96 in the treatment group. The HBeAg clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96, respectively. However, HBV DNA levels ≤ 4 log10 IU/mL were 2.55% and 2.55% at weeks 48 and 96, respectively, and the HBeAg clearance rates were 3.06% and 5.61% at weeks 48 and 96, respectively, in the control group. The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance. CONCLUSION: High rates of HBV DNA reduction, HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments, and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase. The ability of the compound to modulate host immune function probably contributed to this effect.

Two cases of corona virus disease 2019 (COVID-19) treated with the combination of acupuncture and medication in bedridden patients2.

The paper reports the experiences in treatment of two cases of corona virus disease 2019 (COVID-19) with the combination of acupuncture and medication in bedridden patients confirmed in C7 Inpatient Ward, Wuhan Leishenshan Hospital, China. The combined treatment of acupuncture with the oral administration of "Shanghai leishen No.1 formula" was given every day. The prescription was modified weekly according the symptoms of the patients. Besides, the antivirus, anti-infectious and symptomatic treatment of western medicine was combined. Both of the two cases were improved and discharged. It is anticipated that the treatment experiences in these two cases may provide the instruction and enlightenment for the prevention and treatment of COVID-19.

[Quantification of hepatotoxic pyrrolizidine alkaloid adonifoline in traditional Chinese medicine preparations containing Senecionis Scandentis Herba].

Pyrrolizidine alkaloids(PAs) are a kind of natural toxins, which can cause severe hepatotoxicity, pulmonary toxicity, genotoxicity, neurotoxicity, embryotoxicity and even death. Therefore, international organizations and countries such as World Health Organization have paid great attention to herbal medicines and preparations containing PAs. PAs are widely distributed in Chinese herb medicines and contained in hundreds of traditional Chinese medicine preparations. The content of adonifoline, the main PAs in Senecionis Scandentis Herba, shall be less than 0.004% in herbal medicines as described in Chinese pharmacopeia. However, there is no guidance in preparations which contain Senecionis Scandentis Herba. In this study, 14 preparations were analyzed by an UPLC-MS method. Among them, 8 preparations were found to contain adonifoline much higher than the content limits of such countries as Germany, Netherlands and New Zealand. And the highest contents of adonifoline were found in Qianbai Biyan Tablets and Qianbai Biyan Capsules, which are officially recorded in Chinese Pharmacopeia. The contents of adonifoline varied in different batches of the same preparations. The highest content was 156.10 µg·g~(-1) Qianbai Biyan Tablets, whose daily intake of adonifoline was up to 1 030.26 µg according to the recommended dosage of the preparation. Our results showed the potential risk of these preparations, and the content limit of adonifoline shall be inspected Chinese medicine preparations containing Senecionis Scandentis Herba.

Combination of Traditional Chinese Medicine and Low-Molecular-Weight Heparin Prevents Deep Vein Thrombosis After Surgery: A Meta-Analysis.

At present, there is no consistent understanding of the effect of traditional Chinese medicine (TCM) prescription in the prevention of the deep vein thrombosis (DVT), though TCM has been widely used in China. To evaluate the efficacy of TCM prescription combined with low-molecular-weight heparin (LMWH) for preventing DVT after major orthopedics surgery. All the retrieved articles were evaluated using specific inclusion and exclusion criteria. Then, data were extracted and evaluated for inclusion in a randomized controlled trial. In this study, variables included relative risk (RR), mean difference (MD), and their corresponding 95% confidence intervals (95% CIs). Overall, 16 articles were included with 1538 patients, 768 in the combination group (combination of TCM prescription and LMWH) and 770 in the LMWH group. The results indicated that in the combination group, the incidence of DVT (RR: 0.34, 95% CI: 0.23-0.50, P < .00001) and d-dimer levels (standardized mean difference: -1.19, 95% CI: -1.80 to -0.58, P = .0001) was significantly lower than that in the LMWH group. Furthermore, the combination treatment obviously decreased the concentration of fibrinogen (MD: -1.19, 95% CI: -2.13 to -0.25, P = .01). The combination of TCM prescription and LMWH could significantly reduce the incidence of DVT, suggesting that it may be a more effective prophylaxis measure for DVT after major orthopedics surgery.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study.

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

Ce6-Modified Carbon Dots for Multimodal-Imaging-Guided and Single-NIR-Laser-Triggered Photothermal/Photodynamic Synergistic Cancer Therapy by Reduced Irradiation Power.

Photomediated cancer therapy, mainly including photothermal (PT) therapy (PTT) and photodynamic therapy (PDT), has attracted tremendous attention in recent years thanks to its noninvasive and stimuli-responsive features. The single mode of PTT or PDT, however, has obvious drawbacks, either requiring high-power laser irradiation to generate enough heat or only providing limited efficacy due to the hypoxia nature inside tumors. In addition, the reported synergistic PTT/PDT generally utilized two excitation sources to separately activate PTT and PDT, and the problem of high-power laser irradiation for PTT was still not well solved. Herein, a new concept, loading a small amount of photosensitizers onto a PTT agent (both of them can be triggered by a single-near-infrared (NIR) laser), was proposed to evade the shortcomings of PTT and PDT. To validate this idea, minute quantities of photosensitizer chlorin e6 (Ce6) (0.56% of mass) were anchored onto amino-rich red emissive carbon dots (RCDs) that possess superior photothermal (PT) character under 671 nm NIR laser (PT conversion efficiency to be 46%), and meanwhile the PDT of Ce6 can be activated by this laser irradiation as well. The findings demonstrate that Ce6-modified RCDs (named Ce6-RCDs) offer much higher cancer therapy efficacy under a reduced laser power density (i.e., 0.50 W cm-2 at 671 nm) in vitro and in vivo than the equivalent RCDs or Ce6 under the same irradiation conditions. Besides, the Ce6-RCDs also exhibit multimodal imaging capabilities (i.e., fluorescence (FL), photoacoustic (PA), and PT), which can be employed for guidance of the phototherapy process. This study suggests not only a strategy to enhance cancer phototherapy efficacy but also a promising candidate (i.e., Ce6-RCDs) for multimodal FL/PA/PT imaging-guided and single-NIR-laser-triggered synergistic PTT/PDT for cancers by a reduced irradiation power.

Carrier-free nanodrug by co-assembly of chemotherapeutic agent and photosensitizer for cancer imaging and chemo-photo combination therapy.

Nanosized drug delivery systems (NDDS) with photothermal therapy (PTT) and photodynamic therapy (PDT) have been extensively exploited to improve the therapeutic performance and bio-safety of chemotherapeutic drugs in cancer. In this work, a carrier-free nanodrug was developed by co-assembly of the anti-cancer agent ursolic acid (UA), an asialoglycoprotein receptor (ASGPR), which can recognize the target molecule lactobionic acid (LA), and the near-infrared (NIR) probe dye indocyanine green (ICG) to form UA-LA-ICG NPs by a simple and green self-assembly approach. The UA-LA-ICG NPs had suitable stability, showed controlled release profile of UA drugs, and exhibited preferable temperature response (∼59.4 °C) under laser irradiation (808 nm, 1 W/cm2). Compared with free ICG, the UA-LA-ICG NPs significantly enhanced the intracellular ICG uptake. Upon irradiation of the NIR laser, co-assembled nanodrugs demonstrated great performance as a reactive oxygen species (ROS) producer and exhibited more anti-proliferative activities on ASGPR-overexpressing HepG2 cells than ASGPR low-expressing HeLa cells. Meanwhile, in vivo NIR fluorescence imaging exhibited that the co-assembled nanodrugs were specifically targeted to the tumor by the active targeting property of LA, and its circulation time was much longer than that of free ICG. In addition, UA-LA-ICG NPs + NIR irradiation treatment displayed enhanced inhibitory effect on tumor growth in H22 tumor-bearing mice. Overall, the co-assembly of chemotherapeutic agent and photosensitizer by the self-assembly approach might open an alternative avenue and give inspiration to fabricate new carrier-free nanodrugs for cancer imaging and chemo-photo combination therapy. STATEMENT OF SIGNIFICANCE: The present study for the first time reported carrier-free nanoparticles (NPs) by co-assembly of a natural product ursolic acid (UA), an asialoglycoprotein receptor (ASGPR)-recognized sugar molecule lactobionic acid (LA), and the near-infrared dye indocyanine green (ICG) through a simple and green approach. The preparation process of nanodrugs is simple, rapid, effective, and labor-saving. The co-assembled nanodrugs were capable of stabilizing the ICG molecules and specifically targeting to the tumor, which could increase the tumor accumulation in cancer imaging and also enhance the efficacy of chemo-phototherapy.