Vitamin D regulates microflora and ameliorates LPS-induced placental inflammation in rats.

Preeclampsia is a pregnancy-specific disease, which has become an essential cause of perinatal and neonatal death. Gut microflora becomes the regulator of host immunity through the metabolic pathway. Epidemiological studies provide convincing evidence that vitamin D supplementation can prevent the onset of preeclampsia. However, research on the microbial mechanisms and effective treatment strategies for placental inflammation induced by lipopolysaccharide is lacking. In this study, pregnant rats were induced by LPS to establish a rat model of preeclampsia. Sixteen-sequence analysis was used to determine the composition of microflora in feces. In addition, the protective effect of vitamin D supplementation on LPS-preeclampsia rats was evaluated. The results showed that the blood pressure and creatinine of pregnant rats in the LPS group were significantly higher than those in the control group. In addition, LPS disturbed the intestinal microbial community and reduced microbial diversity. Vitamin D supplementation improves the symptoms of preeclampsia, increases the abundance of intestinal beneficial flora, normalizes the level of inflammatory factors LPS-induced by inhibiting the TLR4/MYD88/NF-κB pathway, and effectively resists the disturbance of uterine spiral artery remodeling induced by LPS. This study established that vitamin D-mediated microbial mechanisms and their inhibition are potential therapeutic targets for the treatment of preeclampsia.

1,25(OH)2D3 alleviates LPS-induced preeclampsia-like rats impairment in the protective effect by TLR4/NF-kB pathway.

INTRODUCTION: Accumulating epidemiological studies support that Vitamin D deficiency is associated with the pathogenesis of preeclampsia. However, it is unknown whether vitamin D can be used as a treatment for preeclampsia. This study aimed to explore whether vitamin D supplementation could improve the rat model of preeclampsia. METHODS: LPS was used to establish a rat model of preeclampsia. Inflammatory cytokines were examined by QRT-PCR and ELISA assays, and the concentration of sfit-1 and NO was assessed by ELISA. Analyzing the pathological features of the placenta with hematoxylin-eosin. The spatial learning and memory abilities of offspring were evaluated by the Morris water maze. Immune histology and western blot were performed to evaluate the expression levels of inflammatory pathway-associated Factor and vascular endothelium-associated Factor in the placenta. RESULTS: Vitamin D treatment reduced the blood pressure and urine protein of PE model rats, alleviated pathological damage to the placenta and pregnancy outcomes, and protected PE offspring from impaired memory and learning abilities. Moreover, TLR4 signaling pathway in the placenta was inhibited. Furthermore, vitamin D supplementation increased the expression of endothelial growth factor and vascular relaxing factor, and there was no significant difference compared with the control group. DISCUSSION: We generated the result that Vitamin D supplementation significantly improved the phenotype of preeclampsia and adverse pregnancy outcome caused by an abnormal inflammatory reaction and endothelial dysfunction in the placenta, and improved the learning and cognitive ability of offspring.

Hydrolytically Stable Zr-Based Metal-Organic Framework as a Highly Sensitive and Selective Luminescent Sensor of Radionuclides.

Effective detections of radionuclides including uranium and its predominant fission products, for example, iodine, are highly desired owing to their radiotoxicity and potential threat to human health. However, traditional analytical techniques of radionuclides are instrument-demanding, and chemosensors targeted for sensitization of radionuclides remain limited. In this regard, we report a sensitive and selective sensor of UO22+ and I- based on the unique quenching behavior of a luminescent Zr-based metal-organic framework, Zr6O4(OH)4(OH)6(H2O)6(TCPE)1.5·(H2O)24(C3H7NO)9 (Zr-TCPE). Immobilization of the luminescent tetrakis(4-carboxyphenyl)ethylene (TCPE4-) linkers by Zr6 nodes enhances the photoluminescence quantum yield of Zr-TCPE, which facilitates the effective sensing of radionuclides in a "turn-off" manner. Moreover, Zr-TCPE can sensitively and selectively recognize UO22+ and I- ions with the lowest limits of detection of 0.67 and 0.87 µg/kg, respectively, of which the former one is much lower than the permissible value (30 µg/L) defined by the U.S. EPA. In addition, Zr-TCPE features excellent hydrolytic stability and can withstand pH conditions ranging from 3 to 11. To facilitate real-world applications, we have further fabricated polyvinylidene fluoride-integrating Zr-TCPE as luminescence-based sensor membranes for on-site sensing of UO22+ and I-.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Elimination of amino trimethylene phosphonic acid (ATMP) antiscalant in reverse osmosis concentrate using ozone: Anti-precipitation property changes and phosphorus removal.

Amino trimethylene phosphonic acid (ATMP) was widely used as an antiscalant in reverse osmosis (RO) systems to prevent membrane scaling, and entered RO concentrate at elevated levels. However, phosphonate antiscalants in RO concentrate might aggravate phosphorus pollution, remobilize heavy metals, and adversely affect the sedimentation treatment of RO concentrate. Ozonation was found an efficient method for ATMP treatment. The ATMP removal efficiencies with 8 mg/L ozone were 100% and 86.5% for ultrapure water and RO concentrate, respectively. The ATMP mineralization efficiency reached 46.5% with 8 mg/L ozone. The rate constant for the reaction between ATMP and ozone was 1.92 × 106 M-1 s-1. Increasing the pH from 3 to 9 decreased the ATMP removal efficiency from 90% to 30.9% but increased the orthophosphate formation to ATMP removal ratio from 0.11 to 0.48. The ATMP intermediates generated with low ozone dosages exhibited moderate chelation and anti-precipitation capacity, and their chelation and anti-precipitation capacity could be further attenuated by increasing the ozone dosage. Ozonation alone enhanced the growth potential for microalgae in RO concentrate because orthophosphate formed. Combining ozonation and coagulation effectively removed 83.0% of the total phosphorus from RO concentrate. The maximum algal density of Scenedesmus sp. LX1 decreased by 78.7% by ozonation and coagulation.

Efficiently immobilizing uranium (VI) by oxidized carbon foam.

Oxidized carbon foam (oxidized CF) was prepared by using a facile chemical oxidation treatment at relatively low temperature of 450 °C and applied to capture uranyl cation [U(VI)] from aqueous solutions. The effects of pH, contact time, initial U(VI) concentration, and temperature on the U(VI) absorption performance of oxidized CF were investigated by batch experiments. The oxidized CF was illustrated to exhibit fast sorption kinetics (92% removal within 15 min and 98% removal in 2 h) and high sorption capacity (305.77 mg g-1 at pH 5) toward U(VI). Integrated analyses combining energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy were applied on the U(VI)-loaded oxidized CF, showing the introduction of carboxyl groups as U(VI) sorption sites on the surface of CF after oxidation treatment. Furthermore, extended X-ray absorption fine structure spectroscopy was employed to identify the binding modes of U(VI) indicating that each UO22+ cation is coordinated with one or two carboxyl groups on the equatorial plane. Notably, the low content of U(VI) in wastewater can be efficiently immobilized by the oxidized CF, and the immobilized U(VI) can be further concentrated and converted into Na2U2O7 or U3O8 by a simple sintering step. These findings presented in this work suggest the potential of using oxidized CF for further treatment of low concentration wastewater containing U(VI).

Effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy.@*METHODS@#Twenty children with cerebral palsy (cerebral palsy group) were randomly divided into an acupuncture and rehabilitation group (11 cases) and a rehabilitation group (9 cases), and 10 healthy children were included as the normal group. The rehabilitation group was treated with rehabilitation training, 30 min each time; on the basis of rehabilitation training, the acupuncture and rehabilitation group was treated with acupuncture at Sishenzhen, Zhisanzhen, Naosanzhen, Niesanzhen, Dazhui (GV 14), Shenzhu (GV 12), Mingmen (GV 4), etc. The Sishenzhen (left and right points) and the ipsilateral Niesanzhen were respectively connected with a group of electrodes, intermittent wave, frequency of 2 Hz for 30 min. Both groups were treated once every other day, three times a week, totaling for 3 months. The Gesell developmental diagnostic scale (GESELL) was used to evaluate the developmental quotient (DQ) scores before and after treatment, and the blood samples of children with cerebral palsy before and after treatment and normal children were collected for amino acid metabolomics.@*RESULTS@#Compared before treatment, the DQ scores of adaptation, fine motor and social in the acupuncture and rehabilitation group was increased after treatment (@*CONCLUSION@#Acupuncture combined with rehabilitation training could improve cognitive function in children with cerebral palsy, and the effect may be related to the down-regulation of L-histidine and L-citrulline metabolism.

A study of the home care model based on the Omaha system for elderly maintenance hemodialysis patients / 中华老年医学杂志

Objective:To analyze the application effect of the home care model based on the Omaha system for elderly maintenance hemodialysis patients.Methods:A total of 73 elderly patients undergoing maintenance hemodialysis in the First People's Hospital of Longquanyi District, Chengdu city from December 2018 to December 2019 were enrolled.According to the randomization and double-blind principle, they were divided into the control group receiving the clinical routine care mode(n=32)and the intervention group undergoing the home care mode based on Omaha system(n=41). The Quality of Life Score, care satisfaction and awareness rate of health knowledge of patients were compared between the two groups before and after the care intervention.Results:Compared with before intervention, the quality of life scores was increased after caring in both two groups.And the scores in all dimensions were better in the intervention group than in the control group( t=3.173, 3.833, 3.514 and 4.593, P=0.001, 0.000, 0.000 and 0.000). The awareness rates of nutrition knowledge, water-intaking knowledge, iron supplementation knowledge, potassium and phosphorus limitation and dialysis mode were better in the intervention group than in the control group( χ2=7.592, 5.423, 8.494, 6.161 and 6.962, P=0.011, 0.011, 0.000, 0.010 and 0.011). The total satisfaction rate was 97.6%(40/41)in the intervention group, which was superior to that in the control group(75.0% or 24/32)( χ2 =8.460, P=0.000). Conclusions:The extended home care model based on the Omaha system can effectively improve patients' awareness of health knowledge, improve patients' quality of life and improve the satisfaction with care in elderly maintenance hemodialysis patients with a low education level, and it is worthy of clinical promotion.

UV/chlorine oxidation of the phosphonate antiscalant 1-Hydroxyethane-1, 1-diphosphonic acid (HEDP) used for reverse osmosis processes: Organic phosphorus removal and scale inhibition properties changes.

Reverse osmosis (RO) technology plays an increasingly important role in municipal wastewater reclamation. However, the antiscalants used in RO systems showed adverse effects to the ecosystem: impending the removal of hardness from RO concentrates; inducing phosphorus pollution in receiving water; enhancing the trace metal migration in the environment. In this study, UV/chlorine advanced oxidation process was used to oxidize a typical phosphoric antiscalant (1-Hydroxyethane-1, 1-diphosphonic Acid, HEDP). UV/chlorine showed significant synergetic effects on HEDP degradation compared to UV irradiation or chlorination alone. Compared to UV/H2O2 oxidation, UV/chlorine process is more efficient for HEDP transformation with chlorine dosages ranging from 0.1 to 0.4 mmoL/L. Chorine dosage showed dual effects on HEDP oxidation by UV/chlorine: the increasing trend of transformation efficiency of HEDP got slower with increasing chlorine dosage. The transformation efficiency of HEDP by UV/chlorine oxidation decreased from 39% to 14% with pH increasing from 4.5 to 9.0, likely due to the higher quantum yields and lower radical quenching rates of HOCl than those of OCl-. The transformation efficiency of HEDP decreased 14% and 42% with 30 mM of chloride and bicarbonate, respectively. The presence of nitrate promoted the oxidation of HEDP by UV/chlorine: the transformation efficiency increased 5% and 83% with the presence of 5 mM and 30 mM nitrate, respectively. Based on the static scale inhibition tests, UV/chlorine oxidation is effective at removing the scale inhibition ability of HEDP. During UV/chlorine process, the maximum scale inhibition ratio decreased from 66% to 34% as the removal of phosphonate ligand from HEDP increased to 80%.

2-Phosphonobutane-1,2,4-tricarboxylic acid (PBTCA) degradation by ozonation: Kinetics, phosphorus transformation, anti-precipitation property changes and phosphorus removal.

2-Phosphonobutane-1,2,4-tricarboxylic acid (PBTCA) is an antiscalant that is widely used in reverse osmosis (RO) systems. Because of its high concentration in RO concentrate, eutrophication risk and anti-precipitation properties may affect subsequent treatments, therefore treatment strategies are needed to eliminate such substances. In this study, PBTCA was degraded by ozonation. The results show that PBTCA reacted with ozone molecules and hydroxyl radicals, with second-order rate constants of (0.12 ±â€¯0.002) and (7.83 ±â€¯1.51) × 108 L mol-1 s-1, respectively. The phosphorus in PBTCA (PP) was transformed into organic phosphorus except for PBTCA (PO), and inorganic phosphorus (PI); PO was further transformed into PI. The changes in the concentrations of these phosphorus forms were investigated by model simulation. Simulation showed that the rate of PP transformation into PO was 5.5 times higher than that into PI. PBTCA was ozonated much faster at alkaline pH than at acidic pH. This is ascribed to different amounts of ozone molecules and hydroxyl radicals, and their different reaction rates with PBTCA. Furthermore, anti-precipitation property was reduced during ozonation, as shown by the amounts and morphology changes of the precipitates. PBTCA concentration for 50% anti-precipitation (AP50) did not change during ozonation, indicating that the transformation products generated during ozonation did not have anti-precipitation effects. Phosphorus in PBTCA was removed by ozonation-coagulation treatment. Total phosphorus and inorganic phosphorus were removed efficiently by using ferric chloride as a coagulant. The coagulants tended to bind with inorganic phosphorus to form flocs. Meanwhile, flocs were more easily to aggregate and precipitate as anti-precipitation effect was gradually removed, thus more phosphorus was removed. A combination of ozonation and coagulation removed PBTCA effectively and simultaneously reduced its anti-precipitation property and phosphorus.

Professor 's academic thoughts and acupoint selection experience for hot flashes / 中国针灸

Professor is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between and . While regulating and , more attention should be paid to - harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.

Effect of nitrogen,phosphorus and potassium formula fertilizer on growth and chemical composition content of Inula japonica / 中国中药杂志

Inula japonica was used as the research object, "3414" fertilization experiment were conducted to study the effects of nitrogen,phosphorus and potassium formula fertilizer on the growth and chemical composition content of I. japonica. The characteristics of fertilizer requirement were preliminarily revealed and the study provided fertilization guidance for artificial cultivation of I. japonica. The results showed that different nitrogen,phosphorus and potassium formula fertilizers had significant effects on plant morphology,physiological and biochemical indexes,dry matter accumulation and chemical composition content. The growth indexes and chemical components of I. japonica showed an upward trend with the increase of fertilization amount,especially the nitrogen fertilizer was the most significant. The indicators were analyzed by membership function. After comprehensive evaluation,the optimal nitrogen,phosphorus and potassium formula fertilization level was N3 P2 K2,namely high level nitrogen fertilizer,medium level phosphorus fertilizer and potassium fertilizer. I. japonica is a high fertilizer demand plant,and the rational fertilization scheme is " applying nitrogen fertilizer again and applying phosphorus and potassium fertilizer properly".

Chinese clinical practice guidelines for acute infectious diarrhea in children.

BACKGROUND: The guidelines addressed the evidence-based indications for the management of children with acute infectious diarrhea in Chinese pediatric population. DATA SOURCES: The experts group of evidence development put forward clinical problems, collects evidence, forms preliminary recommendations, and then uses open-ended discussions to form recommendations. The literature review was done for developing this guideline in databases including PubMed, Cochrane, EMBASE, China Biomedical Database, and Chinese Journal Full-text Database up to June 2013. Search the topic "acute diarrhea" or "enteritis" and "adolescent" or "child" or "Pediatric patient" or "Baby" or "Infant". RESULTS: For the treatment of mild, moderate dehydration, hypotonic oral rehydration solutions (ORS) are strongly recommended. Intravenous (IV) rehydration is recommended for severe dehydration, with a mixture of alkali-containing dextrose sodium solution. Nasogastric feeding tube rehydration is used for children with severe dehydration without IV infusion conditions with ORS solution. Regular feeding should resume as soon as possible after oral rehydration or IV rehydration. The lactose-free diet can shorten the diarrhea duration. Zinc supplements are recommended in children with acute infectious diarrhea. Saccharomyces boulardii and Lactobacillus Rhamnus are recommended to be used in acute watery diarrhea. Saccharomyces boulardii is recommended in children with antibiotic-associated diarrhea as well. Montmorillonite and Racecadotril (acetorphan) can improve the symptoms of diarrhea or shorten the course of acute watery diarrhea. Antibiotics are recommended with dysenteric-like diarrhea, suspected cholera with severe dehydration, immunodeficiency, and premature delivery children with chronic underlying disease; otherwise, antibiotics are not recommended. CONCLUSION: The principles of the most controversial treatments with of acute infectious disease are reaching to a consensus in China.

[Thulium laser vaporization versus transurethral resection of the prostate and risk factors for postoperative urethral stricture].

OBJECTIVE: To compare thulium laser vaporization of the prostate (TLVP) and transurethral resection of the prostate (TURP) in the treatment of benign prostate hyperplasia (BPH) analyze the risk factors for postoperative urethral stricture. METHODS: From June 2015 to June 2016, 210 BPH patients in our hospital underwent TURP (n = 126) or TLVP (n = 84). We followed up the patients for 6 months, compared the effects of the two surgical strategies and analyzed the risk factors for postoperative urethral stricture by multivariate logistic regression analysis. RESULTS: Compared with TURP, TLVP achieved significantly shorter time of operation (ï¼»78.6 ± 27.5ï¼½ vs ï¼»53.2 ± 21.6ï¼½ min, P <0.01), postoperative bladder irrigation (ï¼»31.5 ± 2.9ï¼½ vs ï¼»26.1 ± 3.7ï¼½ h, P <0.01), urethral catheterization (ï¼»5.3 ± 1.7ï¼½ vs ï¼»3.7 ± 1.5ï¼½ d, P <0.01) and postoperative hospitalization (ï¼»7.9 ± 2.1ï¼½ vs ï¼»5.5 ± 1.4ï¼½ d, P <0.01) as well as lower urinary leukocyte count at 6 months after surgery (ï¼»32.1 ± 12.6ï¼½ vs ï¼»24.9 ± 11.7ï¼½ /µl, P <0.01) and incidence rate of postoperative complications (11.9% ï¼»15/126ï¼½ vs 3.6% ï¼»3/84ï¼½, P <0.05), particularly that of urethral stricture (7.9% ï¼»10/126ï¼½ vs 1.2% ï¼»1/84ï¼½, P <0.05). Logistic regression analysis showed that the preoperative urinary leukocyte count, postoperative urethral catheterization time, and surgical method were independent risk factors for postoperative urethral stricture. CONCLUSIONS: TLVP, in comparison with TURP, has the advantages of definite effect, fast recovery, high safety and low incidence of postoperative urethral stricture. The main risk factors for postoperative urethral stricture include preoperative urinary tract infection, postoperative urethral catheterization time and surgical method.

Thulium laser vaporization versus transurethral resection of the prostate and risk factors for postoperative urethral stricture / 中华男科学杂志

Objective@#To compare thulium laser vaporization of the prostate (TLVP) and transurethral resection of the prostate (TURP) in the treatment of benign prostate hyperplasia (BPH) analyze the risk factors for postoperative urethral stricture.@*METHODS@#From June 2015 to June 2016, 210 BPH patients in our hospital underwent TURP (n = 126) or TLVP (n = 84). We followed up the patients for 6 months, compared the effects of the two surgical strategies and analyzed the risk factors for postoperative urethral stricture by multivariate logistic regression analysis.@*RESULTS@#Compared with TURP, TLVP achieved significantly shorter time of operation (［78.6 ± 27.5］ vs ［53.2 ± 21.6］ min, P <0.01), postoperative bladder irrigation (［31.5 ± 2.9］ vs ［26.1 ± 3.7］ h, P <0.01), urethral catheterization (［5.3 ± 1.7］ vs ［3.7 ± 1.5］ d, P <0.01) and postoperative hospitalization (［7.9 ± 2.1］ vs ［5.5 ± 1.4］ d, P <0.01) as well as lower urinary leukocyte count at 6 months after surgery (［32.1 ± 12.6］ vs ［24.9 ± 11.7］ /μl, P <0.01) and incidence rate of postoperative complications (11.9% ［15/126］ vs 3.6% ［3/84］, P <0.05), particularly that of urethral stricture (7.9% ［10/126］ vs 1.2% ［1/84］, P <0.05). Logistic regression analysis showed that the preoperative urinary leukocyte count, postoperative urethral catheterization time, and surgical method were independent risk factors for postoperative urethral stricture.@*CONCLUSIONS@#TLVP, in comparison with TURP, has the advantages of definite effect, fast recovery, high safety and low incidence of postoperative urethral stricture. The main risk factors for postoperative urethral stricture include preoperative urinary tract infection, postoperative urethral catheterization time and surgical method.

Magnetic Enrichment of Dendritic Cell Vaccine in Lymph Node with Fluorescent-Magnetic Nanoparticles Enhanced Cancer Immunotherapy.

Dendritic cell (DC) migration to the lymph node is a key component of DC-based immunotherapy. However, the DC homing rate to the lymphoid tissues is poor, thus hindering the DC-mediated activation of antigen-specific T cells. Here, we developed a system using fluorescent magnetic nanoparticles (α-AP-fmNPs; loaded with antigen peptide, iron oxide nanoparticles, and indocyanine green) in combination with magnetic pull force (MPF) to successfully manipulate DC migration in vitro and in vivo. α-AP-fmNPs endowed DCs with MPF-responsiveness, antigen presentation, and simultaneous optical and magnetic resonance imaging detectability. We showed for the first time that α-AP-fmNP-loaded DCs were sensitive to MPF, and their migration efficiency could be dramatically improved both in vitro and in vivo through MPF treatment. Due to the enhanced migration of DCs, MPF treatment significantly augmented antitumor efficacy of the nanoparticle-loaded DCs. Therefore, we have developed a biocompatible approach with which to improve the homing efficiency of DCs and subsequent anti-tumor efficacy, and track their migration by multi-modality imaging, with great potential applications for DC-based cancer immunotherapy.

BA-j as a novel CDK1 inhibitor selectively induces apoptosis in cancer cells by regulating ROS.

Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in cell proliferation and a novel target in the development of anticancer drugs. 8-Hydroxypiperidinemethyl-baicalein (BA-j) is a novel selective CDK1 inhibitor with broad spectrum anti-cancer activity (IC50 12.3 µM) and 2 tumor xenografts. Because of the differential mechanisms controlling redox-states in normal and cancer cells, BA-j can capture oxygen free radicals ((·)O2(-)) and selectively increase the level of H2O2 in cancer cells, thereby specifically oxidize and activate the intrinsic apoptosis pathway bypassing the extrinsic death receptor pathway, thus inducing apoptosis in cancer cells rather than in normal cells. BA-j is different from cytotoxic anticancer drugs which can activate both the intrinsic apoptosis pathway and the extrinsic death receptor pathway, and therefore harm normal cells while killing cancer cells. The molecular and biochemical mechanisms of reactive oxygen species (ROS) regulation suggest that BA-j may be developed into a novel anticancer agent.

Design, synthesis and biological evaluation of N-phenylalkyl-substituted tramadol derivatives as novel µ opioid receptor ligands.

AIM: Tramadol is an atypical opioid analgesic with low potential for tolerance and addiction. However, its opioid activity is much lower than classic opiates such as morphine. To develop novel analgesic and further explore the structure activity relationship (SAR) of tramadol skeleton. METHODS: Based on a three-dimensional (3D) structure superimposition and molecular docking study, we found that M1 (the active metabolite of tramadol) and morphine have common pharmacophore features and similar binding modes at the µ opioid receptor in which the substituents on the nitrogen atom of both compounds faced a common hydrophobic pocket formed by Trp2936.48 and Tyr3267.43. In this study, N-phenethylnormorphine was docked to the µ opioid receptor. It was found that the N-substituted group of N-phenethylnormorphine extended into a hydrophobic pocket formed by Trp2936.48 and Tyr3267.43. This hydrophobic interaction may contribute to the improvement of its opioid activities as compared with morphine. The binding modes of M1, morphine and N-phenethylnormorphine overlapped, indicating that the substituent on the nitrogen atoms of the three compounds may adopt common orientations. A series of N-phenylalkyl derivatives from the tramadol scaffold were designed, synthesized and assayed in order to generate a new type of analgesics. RESULTS: As a result, compound 5b was identified to be an active candidate from these compounds. Furthermore, the binding modes of 5b and morphine derivatives in the µ opioid receptor were comparatively studied. CONCLUSION: Unlike morphine-derived structures in which bulky N-substitution is associated with improved opioid-like activities, there seems to be a different story for tramadol, suggesting the potential difference of SAR between these compounds. A new type of interaction mechanism in tramadol analogue (5b) was discovered, which will help advance potent tramadol-based analgesic design.

Relevant Research on ACE Gene Single Nucleotide Polymorphisms and Premature Coronary Heart Disease Patients with Blood Stasis Syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the relationship between angiotensin converting enzyme (ACE) gene single nucleotide polymorphisms (SNP) and premature coronary heart disease (PCHD) patients with blood stasis syndrome (BSS).</p><p><b>METHODS</b>rs4343, rs4293, and rs4267385 were selected at SNP from ACE gene. Allele and genotype were detected. Frequencies of allele and genotype were compared by using time-of-flight mass spectrometry technique (TOF-MS).</p><p><b>RESULTS</b>Compared with the healthy control group, genotype of rs4293 and rs4267385 in ACE gene were similar, but there was statistical difference in polymorphisms and allele frequencies of rs4343 in the I and II group (P < 0.05, P < 0.01). The frequency of G allele was higher in the 3 groups than in the healthy control group (P < 0.05, P < 0.01). The relative risk analysis showed that the risk for PCHD occurrence in G allele carriers at rs4343 (GG +AG) was 3. 6 times the risk in non-G allele carriers (95% CI: 1.224-10.585, P = 0.02). There was also statistical difference in sex, age, TC, and TG after adjusted Logistic regression analysis (OR = 3.994, 95% CI: 1.230-12.974, P = 0.021).</p><p><b>CONCLUSION</b>The polymorphism at rs4343 (G2350A) might be one of risk factors for PCHD occurrence, but not a predisposing factor for PCHD patients of BSS.</p>