Biocompatible N-carbazoleacetic acid decorated CuxO nanoparticles as self-cascading platforms for synergistic single near-infrared triggered phototherapy treating microbial infections.

In this work, positively charged N-carbazoleacetic acid decorated CuxO nanoparticles (CuxO-CAA NPs) as novel biocompatible nanozymes have been successfully prepared through a one-step hydrothermal method. CuxO-CAA can serve as a self-cascading platform through effective GSH-OXD-like and POD-like activities, and the former can induce continuous generation of H2O2 through the catalytic oxidation of overexpressed GSH in the bacterial infection microenvironment, which in turn acts as a substrate for the latter to yield ˙OH via Fenton-like reaction, without introducing exogenous H2O2. Upon NIR irradiation, CuxO-CAA NPs possess a high photothermal conversion effect, which can further improve the enzymatic activity for increasing the production rate of H2O2 and ˙OH. Besides, the photodynamic performance of CuxO-CAA NPs can produce 1O2. The generated ROS and hyperthermia have synergetic effects on bacterial mortality. More importantly, CuxO-CAA NPs are more stable and biosafe than Cu2O, and can generate electrostatic adsorption with negatively charged bacterial cell membranes and accelerate bacterial death. Antibacterial results demonstrate that CuxO-CAA NPs are lethal against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AREC) through destroying the bacterial membrane and disrupting the bacterial biofilm formation. MRSA-infected animal wound models show that CuxO-CAA NPs can efficiently promote wound healing without causing toxicity to the organism.

[Effects of electroacupuncture on cardiac function and local field potential of sensory and motor cortices in mice with stress cardiomyopathy].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on cardiac function and local field potential (LFP) in sensory and motor cortices in mice with stress cardiomyopathy (SC), and to explore the possible mechanism of EA in improving SC. METHODS: Twenty-seven female C57BL/6 mice were randomized into a blank group, a model group and an EA group, 9 mice in each group. In the model group and the EA group, SC model was established by continuous intraperitoneal injection of isoproterenol (ISO) for 14 days. At the same time of modeling, EA was applied at "Neiguan" (PC 6) and "Shenmen" (HT 7) in the EA group, with disperse-dense wave, in frequency of 2 Hz/15 Hz, 15 min each time, once a day for 14 days. After intervention, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test within 5 minutes were observed; the left ventricular function indexes (left ventricular diameter of end-diastole [LVIDd], left ventricular diameter of end-systole [LVIDs], left ventricular volume of end-diastole [LVEDV], left ventricular volume of end-systole [LVESV], ejection fraction [EF] and fraction shortening [FS]) were detected by echocardiography; the changes in ST-segment amplitude and PR interval of electrocardiogram were observed; the morphology of myocardial tissue was observed by HE staining; the serum levels of cortisol (CORT), cardiac troponin T (cTnT) and brain natriuretic peptide (BNP) were detected by ELISA; the changes of LFP in sensory and motor cortices were recorded by Plexon multi-channel acquisition system. RESULTS: Compared with the blank group, in the model group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were decreased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were increased (P<0.05), EF and FS were decreased (P<0.05); ST-segment amplitude was increased (P<0.05) and PR interval was prolonged (P<0.05); irregular myocardial fiber arrangement, interstitial edema and inflammatory cell infiltration were observed; the serum levels of CORT, cTnT and BNP were increased (P<0.05); in the sensory cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum of theta and beta frequency bands was increased (P<0.05), the power spectral density (PSD) of delta, theta, alpha, beta and gamma frequency bands was increased (P<0.05); in the motor cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum as well as PSD of delta, theta, alpha, beta and gamma frequency bands were increased (P<0.05). Compared with model group, in the EA group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were increased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were decreased (P<0.05), EF and FS were increased (P<0.05); ST-segment amplitude was decreased (P<0.05), and the PR interval was shortened (P<0.05); myocardial fiber injury and inflammatory cell infiltration were reduced; the serum levels of CORT, cTnT and BNP were decreased (P<0.05); in the sensory cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05), the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta, alpha, beta and gamma frequency bands were decreased (P<0.05); in the motor cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05) and the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of delta frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta and gamma frequency bands were decreased (P<0.05). CONCLUSION: EA can improve cardiac function in mice with stress cardiomyopathy, and its mechanism may be related to the regulation of local field potentials in sensory and motor cortices.

[Electroacupuncture improves cognitive impairment of diabetic mice by regulating IRE1α-JNK pathway-related proteins in hippocampus].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the cognitive impairment and expressions of inositol-dependent kinase 1α (IRE1α)/c-Jun N-terminal kinase (JNK) pathway-related proteins in diabetic mice, so as to explore its underlying mechanism. METHODS: Thirty db/db mice were randomly divided into model group (n=15) and EA group (n=15), and 15 db/m mice were chosen as the control group. EA was applied to "Baihui" (GV20) and "Shenting" (GV24), bilateral "Pishu" (BL20) and "Shenshu" (BL23), "Zusanli" (ST36) and "Sanyinjiao" (SP6) for 20 min, and bilateral "Feishu" (BL13), "Hegu" (LI4) and "Taichong" (LR3) were stimulated with filiform needles, with the needles retained for 20 min, once daily, 6 days a week for 4 weeks. The daily food intake, water intake, and weekly body weight and blood glucose of the mice in each group were recorded. The learning and memory abilities were detected by Morris water maze, the morphology of hippocampal cells was observed by HE staining, and IRE1α-JNK pathway-related proteins IRE1α, JNK, anti-apoptotic protein (Bcl-2) were detected by Western blot. RESULTS: Compared with the control group, the food intake, water intake, body weight, blood glucose in the mo-del group were significantly increased (P<0.01), the escape latency was significantly prolonged (P<0.05), the times of cros-sing platform were significantly reduced (P<0.01), and the expression levels of IRE1α and JNK proteins were significantly increased (P<0.01), while the expression of Bcl-2 protein was significantly decreased (P<0.01). Compared with the model group, the food and water intake in the EA group were significantly decreased (P<0.01), the body weight and blood glucose were significantly decreased (P<0.05, P<0.01), the escape latency was significantly shortened (P<0.05), the times of crossing platform significantly increased (P<0.05), and the expression levels of IRE1α and JNK proteins were significantly decreased (P<0.05), while the Bcl-2 expression was significantly increased (P<0.01). The cells in hippocampal CA1 area of mice in the model group are in disorder, with unclear nuclei and obvious vacuoles; while the morphology of nerve cells in EA group was significantly improved. CONCLUSION: EA can improve the cognitive impairment of db/db mice, as well as regulate body weight, blood glucose, and improve the cell morphology in the hippocampus, which may be related to its function in regulating the IRE1α-JNK pathway and related proteins.

[Global centennial research and the internationalization of acupuncture and moxibustion: in the perspective of SCI database (1921-2020)].

The paper retrieves and analyzes SCI articles on acupuncture-moxibustion published in the world from 1921 to 2020. It is found that the overall growth of SCI articles on acupuncture-moxibustion in both China and global countries is increasing, and the proportion of publication amount in China is increased gradually. It is believed that the articles on acupuncture-moxibustion researches from 1921 to 2020 in the world collected in SCI database indicate three stages, i.e. scattered publication, internationalization and great contribution on acupuncture-moxibustion in TCM. The paper investigates the first SCI article on acupuncture-moxibustion in the world and in China respectively and analyzes the main disciplines, research institutions and journal distribution, as well as the highly cited articles in the global countries. It is proposed that acupuncture-moxibustion research in China should reflect the academic ideological characteristics of acupuncture-moxibustion in TCM, develop the interdisciplinary research and deepen the cooperation with high-level scientific institutions so as to improve the international academic influence of acupuncture-moxibustion in TCM.

Different doses of folic acid and vitamin B12 to treat rabbits with deep venous thrombosis and hyperhomocysteinemia.

The effects of different doses of folic acid and vitamin B12 on rabbits with deep vein thrombosis (DVT) and hyperhomocysteinemia were investigated. In total, 60 New Zealand rabbits were divided into untreated control, low-dose and high-dose groups. After inducing DVT, hemorheology and coagulation indexes were measured 3 and 10 days later. We found that both treatment groups performed better than the control group, and the high-dose performed better than the low-dose. Ten days after thrombosis, the levels of Hcy and D-dimer were lower in the high-dose group. Moreover, the changes of lower extremity deep venous thrombosis were significantly reduced in both high- and low-dose groups, but the high-dose group showed the most improvement. The effective rate of the high-dose group was 100%, higher than the rate in the low-dose and control groups. Overall, high-dose of folic acid and vitamin B12 can significantly improve plasma Hcy, coagulation indexes, and pathological changes in the venous thrombosis of the lower extremity.

Dietary maifanite supplementation did not affect the apparent total tract digestibility of calcium and phosphorus in growing pigs.

OBJECTIVE: This study was conducted to determine the effects of dietary maifanite supplementation and fecal collection method on the apparent total tract digestibility (ATTD) of calcium (Ca) and phosphorus (P) and blood parameters in growing pigs. METHODS: Thirty-six growing barrows (Duroc×Landrace×Yorkshire; 27.0±2.6 kg) were allotted to six dietary treatments with 6 pigs per treatment according to body weight in a completely randomized design. The experimental treatments were: i) Low Ca+cornstarch (2.25%), ii) Low Ca+maifanite (2.25%), iii) Medium Ca+cornstarch (1.42%), iv) Medium Ca+maifanite (1.42%), v) High Ca+cornstarch (0.64%), and vi) High Ca+maifanite (0.64%). Feces were collected by the total collection (TC) and indicator method (IM). At the beginning and the end of the experiment, blood samples were collected from each pig. RESULTS: For the TC method, there were no difference in Ca intake, fecal Ca output, Ca retention and the ATTD of Ca between cornstarch and maifanite diets at the same dietary Ca level. However, urinary Ca excretion was lower (p = 0.01) in pigs fed low Ca diets without maifanite supplementation compared with other dietary treatments. Dietary maifanite supplementation had no effect on the P metabolism in growing pigs. For the IM method, there was no difference in Ca digestibility between cornstarch and maifanite diets at the same dietary Ca level. The ATTD of P was greater (p<0.01) in pigs fed the high Ca diet with maifanite supplementation compared with the high Ca diet with cornstarch treatment. Dietary inclusion of maifanite had no effect on blood parameters in growing pigs. CONCLUSION: Dietary maifanite supplementation had no effect on the ATTD of Ca and P and serum parameters in growing pigs. The IM resulted in lower digestibility values than the TC method.

Conventional stents versus stents loaded with (125)iodine seeds for the treatment of unresectable oesophageal cancer: a multicentre, randomised phase 3 trial.

BACKGROUND: The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. METHODS: In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥ 20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with (125)iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. FINDINGS: Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153-201) in the irradiation group versus 147 days (124-170) in the control group (p=0.0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). INTERPRETATION: In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with (125)iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent.

MicroRNA-194 (miR-194) regulates ROMK channel activity by targeting intersectin 1.

The aim of the study is to explore the role of miR-194 in mediating the effect of high-K (HK) intake on ROMK channel. Northern blot analysis showed that miR-194 was expressed in kidney and that HK intake increased while low-K intake decreased the expression of miR-194. Real-time PCR analysis further demonstrated that HK intake increased the miR-194 expression in the cortical collecting duct. HK intake decreased the expression of intersectin 1 (ITSN1) which enhanced With-No-Lysine Kinase (WNK)-induced endocytosis of ROMK. Expression of miR-194 mimic decreased luciferase reporter gene activity in HEK293 T cells transfected with ITSN-1-3'UTR containing the complementary seed sequence for miR-194. In contrast, transfection of miR-194 inhibitor increased the luciferase activity. This effect was absent in the cells transfected with mutated 3'UTR of ITSN1 in which the complimentary seed sequence was deleted. Moreover, the inhibition of miR-194 expression increased the protein level of endogenous ITSN1 in HEK293T cells. Expression of miR-194 mimic also decreased the translation of exogenous ITSN1 in the cells transfected with the ITSN1 containing 3'UTR but not with 3'UTR-free ITSN1. Expression of pre-miR-194 increased K currents and ROMK expression in the plasma membrane in ROMK-transfected cells. Coexpression of ITSN1 reversed the stimulatory effect of miR-194 on ROMK channels. This effect was reversed by coexpression of ITSN1. We conclude that miR-194 regulates ROMK channel activity by modulating ITSN1 expression thereby enhancing ITSN1/WNK-dependent endocytosis. It is possible that miR-194 is involved in mediating the effect of a HK intake on ROMK channel activity.

Effect of zibu shenjing fang (see text) on growth and development of the mouse with kidney-essence insufficiency and study on the mechanism.

OBJECTIVE: To investigate effects of Zibu Shenjing Fang (see text) on growth and development of the mouse with insufficiency ofkidney-essence and the mechanism. METHODS: Total 50 mice were randomly divided into a normal group, a model group, a Jingui Shenqi Wan (see text) group, a Zibu Shenjing Fang high dose group and a Zibu Shenjing Fang low dose group, 10 mice in each group. The kidney-essence insufficiency mouse model was established by use of threat-injuring the kidney combined with over-fatigue. At the same time of modeling, the mice in the model group were intragastrically administrated with saline 20 mL x kg(-1) x d(-1), in the Jingui Shenqi Wan group with suspension of the Jingui Shenqi Wan 2.7 g x kg(-1) x d(-1), in the Zibu Shenjing Fang high dose group with Zibu Shenjing Fang 20 g x kg(-1) x d(-1) and in the Zibu Shenjing Fang low dose group with Zibu Shenjing Fang 10 g x kg(-1) x d(-1), for 21 consecutive days. The general state was observed, the body weight was weighted, and serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) contents were detected. RESULTS: Compared with model group, Zibu Shenjing Fang groups and Jingui Shenqi Wan group could improve manifestation of the mouse with kidney-essence insufficiency, increase body weight of the mouse and serum GH and IGF-1 contents, especially in the high dose group. CONCLUSION: Zibu Shenjing Fang gives play to the function of tonifying the kidney and replenishing essence through regulating GH and IGF-1 levels, so as to influence growth and development of the mouse.

[Analysis of the volatile oils chemical constituents of roots of Actinidia deliciosa].

OBJECTIVE: To analyze the volatile oils chemical constituents of roots of Actinidia deliciosa. METHODS: The volatile oils fraction of roots of Actinidia deliciosa. were extracted by water vapor distilling, and then the constituents were separated and identified, by GC-MS. RESULTS: 16 compounds were identified, accounting for 89.37% of all quantity. CONCLUSION: The principal volatile oils chemical constituents are Phenol, 2,4-bis(1,1-dimethylethl)-; 2-Propenoic acid, 3-(4-methox yphenyl)-, ethyl ester; 9-Octadecenoic acid (Z)-, methyl ester; Cyclotetrasiloxane, octamethyl-.

[Dual-thermotherapy for parenchymal hepatic cells carcinoma].

OBJECTIVE: To study the efficacy and safety of transhepatic arterial "dual-thermotherapy" (DT) for parenchymal hepatic cells carcinoma. METHODS: Fifty patients (mean age 55.5 years, DT group) with parenchymal hepatic cells carcinoma were treated with transhepatic arterial thermochemotherapy with warmed lipiodol (80 degrees C) and warmed chemotherapeutic agents (50 degrees C). Another 50 patients (mean age 54 years) were treated with ordinary transhepatic arterial chemomembolization (TACE) with the same chemotherapeutic drugs but without warming (TACE group). RESULTS: The 1-, 2-, and 3-year survival rates were 77.6%, 53.1% and 46.1%, respectively, in TD group; and 54.4%, 24.2% and 16.1%, resectively, in TACE group; the difference was statistically significant(P<0.05). The sidejeffect of the feeling of cauterization (cases/persistence time) in DT group was statistically significant compared with TACE group (P<0.05), and the difference was not statistically significant about other side-effects. CONCLUSION: Transhepatic arterial perfusion of warmed lipiodol (80 degrees C) and chemotherapeutic agents (50 degrees C), namely, "dual-thermotherapy" is a simple, safe and effective method for treating hepatic carcinoma with less complications than ordinary TACE.

[The effect of shanzha xiaozhi capsule on the blood lipid and the function of endothelial cells in patients with dislipide mia].

OBJECTIVE: To explore the Mechanism of Shanzha xiaozhi Capsule improving the functions of endonthelial cells in patients with dislipide mia. METHODS: To measurate the blood lipid and the levels of plasma Endothelin (ET) and nitrodi oxide (NO) in 30 patients with dislipide mia before and after taking the Shanzha xiaozhi Capsule, and there were 10 normal persons in control group, which were measured the blood lipid and the levels of ET and NO only one time. RESULTS: After treatment with Shanzha xiaozhi Capsule, the levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholestero (LDL-C), ET were markedly reduced (P < 0.05), and the levels of NO were obviously elevated (P < 0.05). CONCLUSION: Shanzha xiaozhi Capsule can reduce blood lipid level and the plasma ET levels, increase the NO levels and the protection to the functions of endothelial cells which might be involved in the mechanisms of against atherosclerosis.

Protein kinase C (PKC)-induced phosphorylation of ROMK1 is essential for the surface expression of ROMK1 channels.

We carried out in vitro phosphorylation assays to determine whether ROMK1 is a substrate of protein kinase C (PKC) and used the two-electrode voltage clamp method to investigate the role of serine residues 4, 183, and 201, the three putative PKC phosphorylation sites, in the regulation of ROMK1 channel activity. Incubation of the purified His-tagged ROMK1 protein with PKC and radiolabeled ATP resulted in (32)P incorporation into ROMK1 detected by autoradiography. Moreover, the in vitro phosphorylation study of three synthesized peptides corresponding to amino acids 1-16, 174-189, and 196-211 of ROMK1 revealed that serine residues 4 and 201 of ROMK1 were the two main PKC phosphorylation sites. In contrast, (32)P incorporation of peptide 174-189 was absent. In vitro phosphorylation studies with ROMK1 mutants, R1S4/201A, R1S4/183A, and R1S183/201A, demonstrated that the phosphorylation levels of R1S4/201A were significantly lower than those of the other two mutants. Also, the Ba(2+)-sensitive K(+) current in oocytes injected with green fluorescent protein (GFP)-R1S4/201A was only 5% of that in oocytes injected with wild type GFP-ROMK1. In contrast, the K(+) current in oocytes injected with GFP-ROMK1 mutants containing either serine residue 4 or 201 was similar to those injected with wild type ROMK1. Confocal microscope imaging shows that the surface expression of the K(+) channels was significantly diminished in oocytes injected with R1S4/201A and completely absent in oocytes injected with R1S4/183/201A. Furthermore, the biotin labeling technique confirmed that the membrane fraction of ROMK channels was almost absent in HEK293 cells transfected with either R1S4/201A or R1S4/183/201A. However, when serine residues 4 and 201 were mutated to aspartate, the K(+) currents and the surface expression were completely restored. Finally, addition of calphostin C in the incubation medium significantly decreased the K(+) current in comparison with that under control conditions. Biotin labeling technique further indicated that inhibition of PKC decreases the surface ROMK1 expression in human embryonic kidney (HEK) cells transfected with ROMK1. We conclude that ROMK1 is a substrate of PKC and that serine residues 4 and 201 are the two main PKC phosphorylation sites that are essential for the expression of ROMK1 in the cell surface.