Tumor microenvironment responsive nano-platform for overcoming sorafenib resistance of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor, which seriously jeopardizes human health. The 5-year relative survival rate of HCC is only about 18%. Sorafenib, a small molecule multi-targeted tyrosine kinase inhibitor (MTKI), has been classified as the first-line treatment scheme for HCC and has significantly extended the median survival time for patients with advanced HCC. Nevertheless, the emergence of sorafenib resistance has substantially hampered its further clinical application. Herein, the nano-platform based on phototherapy and small molecular targeted therapy (SMTT) was devised to overcome the sorafenib resistance and reduce the adverse effects. Hollow mesoporous manganese dioxide (H-MnO2) was prepared by hard template method, and the prepared H-MnO2 was used to load sorafenib and Chlorin e6 (Ce6). Subsequently, the nanoparticle (NPs) were modified with dopamine to optimize biocompatibility. The final prepared NPs (MCS NPs) exhibit regular spherical shape with a hydrated particle size of approximately 97.02 nm. MCS NPs can not only possess tumor microenvironment (TME) stimuli-responsive drug release performance but also can enhance the efficacy of photodynamic therapy and reverse sorafenib resistance by alleviating tumor hypoxia. Under the action of phototherapy (Ce6) combined with molecular targeted therapy (sorafenib), MCS NPs manifest a satisfactory antitumor effect for sorafenib-sensitive or sorafenib-resistant HCC cells, and retain the antiangiogenic properties of sorafenib. In the nude mouse subcutaneous tumor model constructed with sorafenib-resistant cells, MCS NPs demonstrated superior tumor imaging ability and excellent biocompatibility. The tumor inhibition rate of the MCS NPs group without laser irradiation was 53.4 %, while the MCS NPs group with laser irradiation was as high as 100 %. The novel smart TME-responsive nano-platform shows great potential for overcoming sorafenib resistance and realizes multimodality imaging and therapy of HCC.

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION: FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Nanomaterials based on phase change materials for antibacterial application.

Bacterial infections seriously threaten human health. Although antibiotics can significantly treat infectious diseases, antibiotics abuse has brought a series of serious problems, such as multidrug-resistant bacteria, adverse effects, and so on. Therefore, it is indispensable to develop alternative therapies with superior efficacy and minor toxicity to enhance the anti-infective outcome, overcome drug resistance and reduce adverse effects. The phase change material (PCM) is a substance that changes its physical properties with elevated temperatures. Nanoparticles based on PCM have been widely used in biomedical research due to their excellent biocompatibility, sustained release, and outstanding targeting properties. In this manuscript, the applications of PCM-based nanoparticles in the treatment of bacterial infections were summarized. Firstly, the composition and biotoxicity of PCM nanocarriers were described. Secondly, various antibacterial strategies based on PCM nanoparticles for combination therapy were highlighted. Finally, the prospects for antibacterial therapy of PCM nanomaterials were summarized.

Clinical treatment of lumbar disc herniation.

OBJECTIVE: To investigate the clinical effect of radiofrequency ozone and injection of anti-inflammatory analgesic solution into the internal orifice of nerve root combined with traditional Chinese medicine hook operation in the treatment of lumbar disc herniation. METHODS: Patients with lumbar disc herniation who were admitted to our hospital on December 20, 2017 and June 19, 2019 were selected as the main research objects, and the included patients were divided into control group, basic group and comprehensive group by random number table method. Control group was treated with radiofrequency ozone therapy, basic group was treated with injection of anti-inflammatory analgesic solution into the internal orifice of nerve root in addition to the control group, comprehensive group was treated with traditional Chinese medicine hook operation in addition to the basic group. The clinical treatment effects were observed. RESULTS: A total of 153 patients were included in this study, including 40 in the control group, 40 in the basic group, and 73 in the comprehensive group. The results showed that the NRS scores of control group were 3±0.98, 2±0.93 and 2±0.85 at 1 month, 3 months and 1 year after treatment, respectively. NRS scores in the basic group were 3±0.18, 2±0.33, and 2±0.15, respectively. NRS scores in the comprehensive group were 2±0.78, 1±0.54, and 1±0.77, respectively. Compared with the control group, there were significant differences in basic group and comprehensive group at each time point (P < 0. 05). At the same time, compared with the basic group, the NRS score of the comprehensive group was statistically different (P < 0.05). CONCLUSION: Radiofrequency ozone and injection of anti-inflammatory analgesic solution into the internal orifice of nerve root combined with hook operation can obtain good short-term and medium-term effects in the treatment of lumbar disc herniation. It is a safe and effective minimally invasive treatment method. KEY WORDS: Internal orifice of nerve root, Lumbar disc herniation, Ozone.

Chinese medicine Xiaoshui decoction inhibits malignant pleural effusion in mice and mediates tumor-associated macrophage polarization by activating autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoshui decoction (XSD) is a traditional Chinese medicine compound prescription that has been shown to reinforce the spleen and remove the fluid retention, while being widely used in the treatment of malignant pleural effusion (MPE). We previously reported that XSD alleviates symptoms and improves the quality of life in patients with MPE; however, the mechanism employed by XSD on MPE has not yet been elucidated. AIM OF THE STUDY: To investigate the role and mechanism of XSD in inhibiting the development of MPE, and in regulating macrophage polarization in vitro and in vivo. MATERIALS AND METHODS: A murine MPE model was used to study the effect of XSD on MPE. Mice with MPE were randomly allocated to a control group and XSD-low-dose (1.144 g/mL), XSD-middle-dose (2.288 g/mL), XSD-high-dose (4.576 g/mL), or cisplatin groups. RAW264.7 cells were induced to form tumor-associated macrophages (TAMs) as well as M1 and M2 macrophages using different conditioned media in vitro. RESULTS: XSD effectively inhibited MPE formation, reduced pleural permeability and angiogenesis, and prolonged mice survival. Particularly, XSD treatment induced the polarization of TAMs to the M1 phenotype in MPE. Moreover, in-vitro XSD remarkably promoted the expansion of M1 macrophages and reduced M2 macrophages by enhancing autophagy. CONCLUSIONS: XSD inhibits MPE development and regulates macrophage polarization by activating autophagy, indicating that XSD may serve as a novel option for integrative MPE therapies.

Source apportionment of selenium and influence factors on its bioavailability in intensively managed greenhouse soil: A case study in the east bank of the Dianchi Lake, China.

Selenium (Se) is an essential trace element for humans and animals. In China, intensive agricultural inputs in greenhouse vegetable production (GVP) have resulted in great changes in Se concentration and bioavailability in soil, which have great influences on Se flux to living organisms through food chains. It is crucial to understand the factors on Se concentration and bioavailability in greenhouse soil. Thus, we chose the east bank of the Dianchi Lake, a typical GVP area covering 177 km2 in Southwest China, as the study area to quantify source contributions to soil Se and estimate relative importance of influence factors on its bioavailability in GVP with a receptor model (absolute principal component scores-multiple linear regression, APCS-MLR) after principal component analysis (PCA). According to the enrichment factor (EF), total Se in greenhouse soil was accumulated at a minor level (1 < EF < 3) by long-term and intensive fertilization. Source contributions to total Se decreased in the sequence of parent materials > fertilization > atmospheric deposition. It suggested that fertilization, especially manure, might be an important way to increase total Se in greenhouse soils in Se-deficient areas. The bioavailability of Se was affected by several factors, among of which total Se was the foremost one. In comparison with organic matter and clay, Fe/Al oxides exerted more controls on Se bioavailability, which was dependent on pH. Increasing Olsen P was helpful in improving soil Se bioavailability in greenhouse. More attention should be paid to soil physicochemical characteristics when Se-containing fertilizers are applied to increase Se levels in greenhouse vegetables.

Role of Cholinergic Anti-Inflammatory Pathway in Treatment of Intestinal Ischemia-Reperfusion Injury by Electroacupuncture at Zusanli.

Electroacupuncture (EA) at Zusanli is a widely used method for the treatment of intestinal ischemic disease. The current study attempts to investigate the possible mechanism from the point of cholinergic anti-inflammatory pathway (CAP) in rats. Thirty rats were divided into five groups: control group, I/R group, EA group (I/R + EA), PNU group (I/R + α7 nAChR agonist), and α-BGT group (I/R + EA + α7 nAChR antagonist). EA and medicine injection were performed immediately after ischemia. After 2 h of reperfusion, blood and intestine samples were collected and intestinal histopathological score, mRNA expression of mucosal α7 nAChR and NF-κBp65, and serum cytokine levels (IL-6, TNF-α) were examined. Compared with the I/R group, the EA group and PNU group could significantly attenuate the mucosal damage, promote α7 nAChR mRNA expression, and reduce levels of NF-κBp65, IL-6, and TNF-α. Compared with the EA group, α7 nAChR mRNA was decreased, while concentrations of NF-κBp65, IL-6, and TNF-α increased in the α-BGT group. EA at Zusanli could inhibit NF-κBp65 and proinflammatory cytokines production after intestinal I/R injury; its mechanism may be related to the cholinergic anti-inflammatory pathway.

[C, N, P, K Stoichiometric Characteristic of Leaves, Root and Soil in Different Abandoned Years in Loess Plateau].

The research of plant ecological stoichiometry characteristics, nutrients distribution and their changes is of great significance to explain the response and adaptation of plants to environmental change. Leaves, root and soil from eight different abandoned years in Yanhe River basin were selected to study the content, characteristic ratio and distribution of carbon ( C) , nitrogen (N) , phosphorus (P), potassium (K). The results showed that the C, N, P, K contents of plant leaves were 444.21, 22.34, 1.49, 14.66 mg · g⁻¹ respectively, the C/N, C/P, C/K, N/P ratios of plant leaves were 21.86, 424.72, 39.82, 20.27 respectively; the C, N, P, K contents of root were 285.16, 5.79, 0.27, 6.07 mg · g⁻¹ respectively, the C/N, C/P, C/K, N/P ratios of root were .60. 56, 1019.33, 46.55, 21.36 respectively; the C, N, P, K contents of soil were 2.28, 0.18, 0.28, 4.33 mg · g⁻¹ respectively, the C/N, C/P, C/K, N/P ratios of soil were 16.43, 8.40, 0.54, 0.66 respectively. During the abandoned year of 1-35, C content of leaves increased, N content increased and then declined, P content declined overall, K content declined and then increased. The C/N, C/P, C/K, N/P ratios of plant leaves showed a rising trend overall. The changing pattern of root was different from that of leaves. Along with the increasing rehabilitation age, C and N contents of soil increased, P content changed as arc-sin function, K content changed as parabola, C/N decreased, C/P, C/K, N/P increased. With the increase of Abandoned Years, the ratio of C, P, K contents in leaves and root decreased, the ratio of C, N, P contents in leaves and soil decreased, the ratio of C, N contents in root and soil decreased. Corresponding relationship and its intension between different abandoned years and plant nutrient limit status and its allocation pattern were different.

Synergistic Effects of Electroacupuncture and Mesenchymal Stem Cells on Intestinal Ischemia/Reperfusion Injury in Rats.

Electroacupuncture (EA) and transplantation of bone marrow mesenchymal stem cells (MSCs) are both promising therapeutic applications for intestinal disorders. The current study examined their combined effect on rat intestinal ischemia/reperfusion (I/R) injury and the possible mechanism. Five groups were performed: con group (shame operation),I/R group (model group), MSC group (I/R + MSC), EA group (I/R + EA), and combined group (I/R + MSC + EA). Intestinal histological damage, crypt cell proliferation degree, mucosal cytokines expression, and levels of inflammation factors were studied for each group. Compared with the I/R group, crypt cell proliferation index and mucosal mRNA concentration of SDF-1, CXCR4, EGF, EGFR in MSC group and EA group were significantly increased, with mucosal NF-кBp65 and serum inflammation factor (TNF-α, IL-6) levels significantly decreased. Above all of these indicators except NF-кBp65 were improved more notably in combined group than the other two treatment groups. Chiu's score was only ameliorated remarkably in the combined group. The combined treatment of MSC transplantion and electroacupuncture could protect intestinal mucosal barrier from I/R injury.

[A clinical research on renal protective effect of Xuebijing injection in patients with sepsis].

OBJECTIVE: To evaluate the protective effect of Xuebijing injection against renal injury in patients with sepsis, and to explore its possible mechanism. METHODS: A prospective randomized controlled trial (RCT) was conducted in which 62 severe patients with sepsis and septic shock admitted in Department of Critical Care Medicine of Jiangsu Province Traditional Chinese Medicine Hospital from June 2013 to December 2013 were randomly divided into control group and Xuebijing group, with 31 patients in each group. The patients in both groups received basic treatment for sepsis, and the patients in Xuebijing group were additionally given intravenous injection of Xuebijing 100 mL once a day for 7 days. In both groups, the changes in acute physiology and chronic health evaluation II (APACHE II) score were observed before treatment and 1, 3, 7 days after treatment, and the changes in the levels of interleukins (IL-6, IL-10), prothrombin time (PT), fibrinogen (Fib), activated partial thromboplastin time (APTT), serum creatinine (SCr), and Cystain C (Cys C) were determined before treatment and 1 day and 3 days after treatment. RESULTS: There was no statistically significant difference in APACHE II score before treatment between two groups, however, the APACHE II scores were significantly decreased in both groups 3 days and 7 days after treatment compared with those before treatment, and the degree of decrease in Xuebijing group was more obvious 7 days after treatment (13.61±7.62 vs. 16.34±8.70, P < 0.05). Serum concentrations of Cys C, SCr, IL-6, IL-10, PT, APTT, and Fib showed no difference between two groups before treatment (all P > 0.05), while after treatment the degrees of improvement of above indexes in Xuebijing group were obviously superior to those in control group, especially 3 days after treatment[Cys C (mg/L): 1.12±0.11 vs. 1.35±0.14, SCr (µmol/L): 115.0±31.0 vs. 135.0±24.0, IL-6 (ng/L): 54.27±28.79 vs. 73.35±31.01, PT (s): 13.50±0.11 vs. 15.71±0.11, APTT (s): 43.66±0.31 vs. 48.03±0.55, Fib (g/L): 1.91±0.51 vs. 1.51±0.52, P < 0.05 or P < 0.01]. CONCLUSIONS: Xuebijing injection has certain renal protective effect in patients with sepsis, and its mechanism is possibly related to the regulation and improvement of uncontrolled inflammatory response and coagulation function in sepsis.

[Changes of cell factor in bronchoalveolar lavage fluid in rats exposed to silica].

OBJECTIVE: To investigate the changes in the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in rats exposed to silica dust. METHODS: Experimental rats were randomly divided into control group and three experimental groups (doses of dust: 15, 30, and 60 mg/ml), with 42 rats in each group. Each rat in the control group was treated with 1 ml of normal saline by intratracheal instillation, while each rat in the experimental groups was exposed to 1 ml of silica suspension by a single intratracheal instillation. Seven rats in each group were killed at 1, 3, 7, 14, 21, and 28 days after exposure, and then BALF was collected. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin (IL)-1, IL-6, IL-16, macrophage inflammatory protein-1 alpha (MIP-1α), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and transforming growth factor-ß (TGF-ß). RESULTS: The levels of cytokines in each experimental group were higher than those in the control group at any time point. In the early stage of exposure (day 1-3), BALF IL-1 level increased significantly with the increase in dust dose, and on day 14, BALF IL-6 and IL-16 levels increased significantly with the increase in dust dose; the levels of IL-1, IL-6, and IL-16 in the experimental groups reached the peak on day 14. There were significant differences in the levels of MIP-1α and MCP-1 between the experimental groups (FMIP-1α = 30.106, P<0.01; FMCP-1 = 17.193, P<0.01). In each group, the level of MCP-1 varied significantly at different time points (F = 0.618, P>0.05). On day 1-14, BALF TNF-α level increased with the increase in dust dose, with a significant dose-response relationship (P < 0.05). In each experimental group, TNF-α level reached the peak on day 14. On days 14, 21, and 28, the high-dose group had significantly higher BALF TGF-ß levels than the low-dose group (P<0.05); on days 14 and 28, the high-dose group had significantly higher BALF TGF-ß levels than the middle-dose group (P<0.05). CONCLUSION: IL-1, IL-6, IL-16, MIP-1α, MCP-1, and TNF-α play a role in the development and progression of silicosis inflammation. TGF-ß may be related to (related to; associated with; correlated with) fibrosis.

[Scavenging effect of Sarcandra glabra powder on radiation-induced reactive oxygen species in the parotid gland of miniature pigs].

OBJECTIVE: To investigate the effect of Sarcandra glabra in scavenging reactive oxygen species (ROS) produced by γ-ray irradiation in the parotid gland of miniature pigs. METHODS: Forty-five male miniature pigs were randomly divided into control group, radiation group and radiation plus medication group, and each group contained 3 parallel groups (subgroups a, b and c). From 1 week before exposure of the parotid gland region to 15 Gy γ-ray irradiation (which was not administered in the control group), the miniature pigs in radiation plus medication group were given Sarcandra glabra powder, while those in the other groups received an equal amount of saline. Bilateral parotid glands were taken and weighed on the days 10, 40 and 90 following the exposure in subgroups a, b, and c, respectively, and ROS content in the parotid glands were determined by enzyme-linked immunosorbent assay. RESULTS: The content of ROS was significantly lower in radiation plus medication group than in the radiation group (P<0.01). In the radiation plus medication group, the ROS content showed no significant difference between subgroups a and b or between subgroups a and c (P>0.01), but differed significantly between subgroups b and c (P<0.01). Sarcandra glabra showed a strong ROS-scavenging effect 10 days after the irradiation, and the ROS content was similar with that in the control group (P>0.01); at 40 and 90 days, the ROS-scavenging effect of Sarcandra glabra was still observable, but the ROS content was significantly higher in the irradiation plus medication group than in the control group (P<0.01). CONCLUSION: Sarcandra glabra displays a ROS-scavenging effect in the parotid gland of miniature pigs against irradiation, especially at 10 days following the exposure, which may serve as the main mechanism for the protective effect of Sarcandra glabra against radiation injury in the parotid gland.

[Study on the identification of tea using near infrared reflectance spectroscopy].

A rapid tea identification method by near infrared spectroscopy coupled with pattern recognition based on principal components analysis and Mahalanobis' distance technique was proposed. Four famous brand teas in China were studied, including Longjing tea, Biluochun tea, Maofeng tea and Tieguanyin tea in the experiment. In the spectral region between 6 500 and 5 300 cm(-1), through preprocessing method of MSC (multiplicative scatter comection), the prediction model was built. The result showed that the model was the best with 8 principal component factors. The rates of identification in calibration set samples and prediction set samples were 98.75% and 95%, respectively. A new idea about quick and precise identification of tea was offered.