P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult.

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

Intrauterine fetal death due to rupture of umbilical vessels: a rare case of furcate cord insertion.

Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes.

[Pueraria lobate advances in molecular pharmacognosy].

Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients.

Magnetic hierarchical porous SiO2 microparticles from droplet microfluidics for water decontamination.

A simple and flexible strategy based on droplet microfluidics is developed for controllable fabrication of uniform magnetic SiO2 microparticles with highly-interconnected hierarchical porous structures for enhanced water decontamination. Uniform precursor water droplets containing surfactants and homogenized fine oil droplets with a relatively high volume ratio are generated from microfluidics as templates for microparticle synthesis via hydrolysis/condensation reaction. The SiO2 microparticles possess hierarchical porous structures, containing both mesopores with size of several nanometers, and well-controlled and highly-interconnected macropores with size of hundreds of nanometers. The SiO2 microparticles synergistically integrate fast mass transfer and large functional surface area for enhanced adsorption. To demonstrate the enhanced adsorption performances for organic dyes and toxic heavy metal ions, the microparticles are respectively used for removal of methylene blue in water, and modified with thiol-groups for removal of Pb2+ ions in water. Meanwhile, the microparticles can be easily recycled by magnetic field for reuse.

Effects of electromagnetic pulse exposure on gelatinase of blood-brain barrier in vitro.

The biological effects of electromagnetic pulse (EMP) on the brain have been focused on for years. It was reported that gelatinase played an important role in maintaining brain function through regulating permeability in the blood-brain barrier (BBB). To investigate the effects of EMP on gelatinase of BBB, an in vitro BBB model was established using primary cultured rat brain microvascular endothelial cells (BMVEC), astrocytes and half-contact culture of these cells in a transwell chamber. Cultured supernatant and cells were collected at different time points after exposure to EMP (peak intensity 400 kV/m, rise time 10 ns, pulse width 350 ns, 0.5 pps and 200 pulses). Protein levels of cellular gelatinase MMP-2 and MMP-9, and endogenous inhibitor TIMP-1 and TIMP-2 were detected by Western blot. The activity of gelatinase in culture supernatant was detected by gelatin zymography. It was found that compared with the sham-exposed group, the protein level of MMP-2 was significantly increased at 6 h (p < 0.05), and the protein level of its endogenous inhibitor TIMP-2 did not change after EMP exposure. In addition, the protein levels of MMP-9 and its endogenous inhibitor TIMP-1 did not change after EMP exposure. Gelatin zymography results showed that the activity of MMP-2 in the inner pool and the outer pool of the transwell chamber was significantly increased at 6 h after EMP exposure compared with that of the sham group. These results suggested that EMP exposure could affect the expression and activity of MMP-2 in the BBB model.

[Two new flavonoid glycosides from Nervilia fordii].

Two new flavonoid glycosides were isolated from the aerial parts of Nervilia fordii by various chromatographies such as D101 macroporous resin, ODS and preparative HPLC chromatographic techniques. Their structures were elucidated as rhamnocitrin-3-O-ß-glucopyranosyl-4'-O-ß-galactosyl-(1→3)-glucopyranoside(1) and 7,3'-di-O-methylquercetin-4'-O-[ß-galactosyl-(1→3)-ß-glucopyranosyl]-3-O-ß-glucopyranoside(2) on the basis of extensive spectroscopic analyses, including 1D-, 2D-NMR, HR-ESI-MS and analytical hydrolysis.

Myeloid-specific tristetraprolin deficiency in mice results in extreme lipopolysaccharide sensitivity in an otherwise minimal phenotype.

Tristetraprolin (TTP) is a mRNA-destabilizing protein that binds to AU-rich elements in labile transcripts, such as the mRNA encoding TNF, and promotes their deadenylation and degradation. TTP-deficient (knockout [KO]) mice exhibit an early-onset, severe inflammatory phenotype, with cachexia, erosive arthritis, left-sided cardiac valvulitis, myeloid hyperplasia, and autoimmunity, which can be prevented by injections of anti-TNF Abs, or interbreeding with TNF receptor-deficient mice. To determine whether the excess TNF that causes the TTP KO phenotype is produced by myeloid cells, we performed myeloid-specific disruption of Zfp36, the gene encoding TTP. We documented the lack of TTP expression in LPS-stimulated bone marrow-derived macrophages from the mice, whereas fibroblasts expressed TTP mRNA and protein normally in response to serum. The mice exhibited a minimal phenotype, characterized by slight slowing of weight gain late in the first year of life, compared with the early-onset, severe weight loss and inflammation seen in the TTP KO mice. Instead, the myeloid-specific TTP KO mice were highly and abnormally susceptible to a low-dose LPS challenge, with rapid development of typical endotoxemia signs and extensive organ damage, and elevations of serum TNF levels to 110-fold greater than control. We conclude that myeloid-specific TTP deficiency does not phenocopy complete TTP deficiency in C57BL/6 mice under normal laboratory conditions, implying contributions from other cell types to the complete phenotype. However, myeloid cell TTP plays a critical role in protecting mice against LPS-induced septic shock, primarily through its posttranscriptional regulation of TNF mRNA stability.

Genetic polymorphisms in inflammatory response genes and their associations with breast cancer risk.

AIM: To explore the association of NFKB1 c.-798_-795delATTG (rs28362491), NFKBIA c.-949C>T (rs2233406), IL-8 c.-352A>T (rs4073), IL-10 c.-854T>C (rs1800871), TNF c.-418G>A (rs361525), and TNF c.-488G>A (rs1800629) polymorphisms with breast cancer risk in an East Chinese population. METHODS: We conducted a case-control study including 975 study participants (474 breast cancer patients and 501 female controls without cancer) and genotyped the polymorphisms employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was used to assess the association of the polymorphisms with breast cancer risk. RESULTS: We found that the ins/del and del/del genotypes of NFKB1 polymorphism and TT genotype of IL-10 polymorphism significantly increased breast cancer risk (NFKB1 ins/del odds ratio [OR] 1.69, 95% [CI] 1.23-2.33, P=0.001; NFKB1 del/del OR 2.42, 95% CI 1.72-3.42, P<0.001; IL-10 TT OR 2.36, 95% CI 1.58-3.52, P<0.001). On the other hand, the TT genotype of IL-8 polymorphism, GA and AA genotypes of TNF c.-418G>A polymorphism, and GA genotype of TNF c.-488G>A polymorphism significantly reduced breast cancer risk (IL-8 TT OR 0.48, 95% CI 0.33-0.72, P<0.001; TNF c.-418 GA OR 0.58, 95% CI 0.41-0.80, P=0.001; TNF c.-418 AA OR 0.38, 95% CI 0.14-0.98, P=0.044; TNF c.-488 GA OR 0.68, 95% CI 0.48-0.96, P=0.029). When stratified by menopausal status, the CT genotype of NFKBIA polymorphism significantly reduced the risk among pre-menopausal women (OR 0.63, 95% CI 0.40-0.99, P=,043), but not among post-menopausal women. CONCLUSIONS: NFKB1, NFKBIA, IL-8, IL-10, and TNF polymorphisms could serve as useful predictive biomarkers for breast cancer risk among women in East China.

Clinical efficacy and safety of flexible ureteroscopy and percutaneous nephrolithotomy for large kidney stones: A retrospective comparative study.

BACKGROUND: Renal stones ranging 20-40 mm are very common in China. Although no large-sample clinical studies have confirmed the clinical efficacy and safety of this method, there is also a lack of comparative data with traditional treatment. AIM: To investigate the clinical efficacy of flexible ureteroscopy (FURS) and percutaneous nephrolithotomy (PCNL) by postoperative stone clearance and changes in soluble vascular cell adhesion molecule 1 (sVCAM-1) and kidney injury molecule 1 (KIM-1) levels in patients with large kidney stones (> 2 cm in diameter). METHODS: This single-center observational study was performed at a Chinese hospital between January 1, 2021, and October 30, 2023. All 250 enrolled patients were diagnosed with large kidney stones (> 2 cm) and divided into a FURS group (n = 145) and a PCNL group (n = 105) by the surgical method. The FURS group was treated with flexible ureteroscopy and the PCNL group was treated with percutaneous nephrolithotomy. The operation time, time to palinesthesia, intraoperative blood loss, drop in hemoglobin, length of hospital stay, stone clearance rate, and complications were recorded in the two groups. Preoperative and postoperative serum sVCAM-1 levels, erythrocyte sedimentation rate (ESR), urine KIM-1 levels, preoperative and postoperative pain visual analog scale (VAS) and Wisconsin Stone Quality of Life Questionnaire (WISQOL) scores were also documented. RESULTS: All 250 eligible patients completed the follow-up. There were no significant differences in baseline characteristics between the two groups (P > 0.05). The operation time in the FURS group was significantly greater than that in the PCNL group. The time to ambulation, intraoperative blood loss, decrease in hemoglobin, and length of hospital stay were significantly lower in the FURS group than in the PCNL group. The FURS group also had a significantly higher stone clearance rate and a lower incidence of postoperative complications. There was no significant difference in antibiotic use between the groups. Postoperative serum sVCAM-1 levels, urine KIM-1 levels, and VAS scores were lower in the FURS group than in the PCNL group, but postoperative ESR and WISQOL scores were greater in the FURS group than in the PCNL group. CONCLUSION: FURS demonstrated superior clinical efficacy in treating large kidney stones (> 2 cm in diameter) compared PCNL. It not only improved the postoperative stone clearance rate and reduced complications and recovery time but also positively affected serum SCM-1, ESR, and urine KIM-1 levels, subsequent improvement of patient quality of life.

Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for ≥ 5 cm hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks sixth globally in cancer incidence and third in mortality rates. Unfortunately, over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations, poor physical condition, and limited organ availability upon diagnosis. Clinical guidelines endorse transarterial chemoembolization (TACE) as the frontline treatment for intermediate to advanced-stage HCC. Cryoablation (CRA) is an emerging local ablative therapy increasingly used in HCC management. Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects, potentially improving long-term survival rates. However, the superiority of combined TACE + CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation. AIM: To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of ≥ 5 cm. METHODS: PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022. Meta-analysis was performed using RevMan 5.3 software. RESULTS: After screening according to the inclusion and exclusion criteria, 6 articles were included, including 2 randomized controlled trials and 4 nonrandomized controlled trials, with a total of 575 patients included in the meta-analysis. The results showed that the objective response rate [odds ratio (OR) = 2.56, 95% confidence interval (CI):1.66-3.96, P < 0.0001), disease control rate (OR = 3.03, 95%CI: 1.88-4.89, P < 0.00001), 1-year survival rate (OR = 3.79, 95%CI: 2.50-5.76, P < 0.00001), 2-year survival rate (OR = 2.34, 95%CI: 1.43-3.85, P = 0.0008), and 3-year survival rate (OR = 3.34, 95%CI: 1.61-6.94, P = 0.001) were all superior to those of the control group; the postoperative decrease in alpha-fetoprotein value (OR = 295.53, 95%CI: 250.22-340.85, P < 0.0001), the postoperative increase in CD4 value (OR = 10.59, 95%CI: 8.78-12.40, P < 0.00001), and the postoperative decrease in CD8 value (OR = 6.47, 95%CI: 4.44-8.50, P < 0.00001) were also significantly higher than those in the TACE-alone treatment group. CONCLUSION: Compared with TACE-alone treatment, TACE + CRA combined treatment not only improves the immune function of HCC patients with a diameter of ≥ 5 cm, but also enhances the therapeutic efficacy and long-term survival rate, without increasing the risk of complications. Therefore, TACE + CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of ≥ 5 cm.

Designing and preparing supramolecular encapsulation systems based on fraxetin and cyclodextrins for highly selective detection of nicotine.

Herein, a series of water-soluble supramolecular inclusion complexes (ICs) probes were prepared using cyclodextrins (CDs) and fraxetin (FRA) to detect nicotine (NT) with high selectivity in vitro and in vivo. The FRA/CD ICs prepared through the saturated solution method exhibited excellent water solubility, stability, and biocompatibility. A clear host-guest inclusion model was provided by the theoretical calculations. The investigation revealed that NT was able to enter into the cavities of FRA/ß-CD IC and FRA/γ-CD IC, and further formed charge transfer complexes with FRA in the CD cavities, resulting in a rapid and highly selective fluorescence-enhanced response with the lowest detection limits of 1.9 × 10-6 M and 9.7 × 10-7 M, and the linear response ranged from 0.02 to 0.3 mM and 0.01-0.05 mM, respectively. The IC probes showed good anti-interference performance to common interferents or different pH environments, with satisfactory reproducibility and repeatability of response to NT. Furthermore, the potentiality of the probes was confirmed through fluorescence imaging experiments using human lung cancer cells and the lung tissue of mice. This study offers a fresh perspective for detecting NT in environmental and biomedical analysis.

[Analysis of resistance tendency of bloodstream-infecting pathogens in China].

OBJECTIVE: To investigate the resistance profiles and the trend of bloodstream-infecting pathogens isolated from hospitalized patients during 2004-2010. METHODS: The bloodstream isolates were collected from 18 hospitals in 17 cities. Minimum inhibition concentrations (MIC) were determined using the agar dilution method recommended by CLSI (Clinical and Laboratory Standards Institute), and susceptibility results were analyzed according to the 2011 CLSI guideline. RESULTS: Among the 2004-2005, 2007-2008 and 2009-2010 periods, the proportions of clinical isolates were similar; 43.1% (149 isolates), 34.0% (151 isolates) and 47.5% (776 isolates) for Gram positive strains, 56.9% (197 isolates), 66.0% (293 isolates) and 52.5% (858 isolates) for Gram negative strains, respectively. The isolating rate of MRSA was 54.1% (20/37) in 2007-2008, which was the highest among the 3 periods during 2004 to 2010, while it decreased in 2009-2010 (36.5%, 62/170). The MRCNS proportions were similar across the 3 periods. One (1.8%) vancomycin-resistant Enterococcus faecium and 1 linezolid-resistant Enterococcus faecalis were found. Although the isolating rates of penicillin non-sensitive strains (oral) were similar between 2009-2010 and 2007-2008 [54.5% (6/11) and 53.9% (7/13), respectively], the resistant rates increased from 0% in 2007-2008 to 30.8% (4/13) in 2009-2010. The results were similar according to the non-meningitis criterion (IV), and the susceptibility rates decreased from 100.0% (11 isolates) in 2007-2008 to 84.6% (11/13) in 2009-2010. ESBL-harboring strains in E. coli were similar among the 3 periods during 2004 to 2010 [66.7% (30/45), 73.2% (71/97) and 67.9% (233/343), respectively]. ESBL-producing strains in Klebsilla pnuemoniae decreased year after year, 72.4% (21/29), 50.0% (18/36) and 41.1% (65/158) in 2004-2005, 2007-2008 and 2009-2010, respectively. Except that the sensitive rate of Enterobacter cloacae to ertapenem was 80% (32/40), the sensitive rates of other strains to carbapenems were still above 90% and the resistance rates were less than 5%. Acinetobacter baumannii had the highest multi-drug resistance rate (81.8%, 81/99). One strain (1.0%, 1/99) of Acinetobacter baumannii isolated in 2009-2010 was reported to be pan-resistant. CONCLUSIONS: We are facing a more serious situation of bacterial resistance. Acinetobacter baumannii resistance was most serious, usually with the characteristics of multiple drug resistance, and even pan-resistance. Carbapenems remain to be the most effective against enterobacteriaceae. Strains resistant to novel antibiotics (linezolid and tigecycline) have emerged.

Occurrence of antibiotics in reclaimed water, and their uptake dynamics, phytotoxicity, and metabolic fate in Lolium perenne L.

Reclaimed water (RW) has been extensively used for irrigation in agriculture, yet the occurrence of antibiotics in real RW, and their toxicity, uptake dynamics and metabolic fate still needs comprehensive exploration. In this study, we investigated the residual concentrations of nineteen antibiotics in the RW from four wastewater treatment plants, and determined their toxicity on plant at environment-relevant concentration. Total found concentrations of these antibiotics ranged from 623.66 ng L-1 to 1536.96 ng L-1, which decreased 10.3 and 19.4 % of roots' length and weight. Uptake dynamics analysis of the most hazardous antibiotic, norfloxacin (NFX) showed increasing amounts in the roots and leaves up to 3087.71 µg g-1. Ryegrass also can remove >80 % of 100 µg L-1 NFX being achieved by biodegradation through ring cleavage, decarboxylation, defluorination, hydrogenation, methylation and oxidation. Toxicity assessment of the identified byproducts showed their more toxic effect on fish, daphnia and algae. This study extended our understanding of the fate of antibiotics in plants during irrigation with reclaimed water, and emphasized its safety and pollutants' biomagnification concerns.

PKC and RhoA signals cross-talk in Escherichia coli endotoxin induced alterations in brain endothelial permeability.

Escherichia coli endotoxin LPS regulates blood-brain barrier permeability by disrupting the tight junction (TJ) complex between brain endothelial cells. This study used Bend.3 cells to examine the signaling networks involved in the hyperpermeability of the brain endothelial barrier caused by LPS. The LPS-induced alterations in the brain endothelial barrier were associated with PKC (a, ß, ζ) and RhoA, but were independent of PI3K and the tyrosine kinase pathway. Inhibition of PKC (a, ß, ζ) and RhoA activity using shRNA and dominant negative mutants diminished the effects of LPS on the brain's endothelial TJs. The interactions between the PKC and Rho pathways were therefore examined. PKC-a and PKC-ζ, but not PKC-ß interacted with RhoA in Bend.3 cells stimulated by LPS. PKC-a acted as the upstream molecule for Rho and PKC-ζ acted as the downstream target for Rho. Comparing the effect of double inhibition of "Rho and PKC" and single inhibition of "Rho" or "PKC" confirmed that this interaction is critical for LPS-induced brain endothelial cell hyperpermeability. Collectively these data are the first to suggest that LPS affects the brain's endothelial TJ barrier via PKC (a, ß, ζ)- and RhoA, independent of the PI3K and tyrosine kinase pathways. In addition, PKC-a and PKC-ζ, respectively, act as the upstream and downstream regulator for RhoA in the process.

Interleukin-1ß and microRNA-146a in an immature rat model and children with mesial temporal lobe epilepsy.

PURPOSE: Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of mesial temporal lobe epilepsy (MTLE). The aim of this study was to investigate the dynamic expression of interleukin (IL)-1ß as a proinflammatory cytokine and microRNA (miR)-146a as a posttranscriptional inflammation-associated microRNA (miRNA) in the hippocampi of an immature rat model and children with MTLE. METHODS: To study the expression of IL-1ß and miR-146a, we performed a reverse transcription polymerase chain reaction, Western blot, and real-time quantitative PCR on the hippocampi of immature rats at 11 days of age. Expression was monitored in the acute, latent, and chronic stages of disease (2 h and 3 and 8 weeks after induction of lithium-pilocarpine status epilepticus, respectively), and in control hippocampal tissues corresponding to the same timeframes. Similar expression methods were applied to hippocampi obtained from children with MTLE and normal controls. KEY FINDINGS: The expression of IL-1ß and miR-146a in both children and immature rats with MTLE differs according to the stage of MTLE development. Both IL-1ß and miR-146a are significantly up-regulated, but in opposite ways: IL-1ß expression is highest in the acute stage, when expression of miR-146a is at its lowest level; miR-146a expression is highest in the latent stage, when IL-1ß expression is at its lowest level. Both IL-1ß and miR-146a are up-regulated in the chronic stage, but not as much as in the other stages. SIGNIFICANCE: Our study is the first to focus on the expression of miR-146a in the immature rat model of lithium-pilocarpine MTLE and in children with MTLE. We have detected that the expression of proinflammatory cytokine IL-1ß and posttranscriptional inflammation-associated miR-146a is variable depending on the disease stage. Furthermore, both IL-1ß and miR-146a are up-regulated in immature rats and children with MTLE. Our findings elucidate the role of inflammation in the pathogenesis of MTLE in the immature rat model and children. Therefore, modulation of the IL-1ß-miR-146a axis may be a novel therapeutic target in the treatment of MTLE.

Altered expression of matrix metalloproteinases and tight junction proteins in rats following PEMF-induced BBB permeability change.

OBJECTIVE: To investigate the expression of occludin, ZO-1, MMP-2, and MMP-9 in cerebral microvasculature following Pulse Electromagnetic Field (PEMF) induced BBB permeability change. METHODS: Sprague-Dawley rats were randomized into PEMF and sham exposed groups (n = 8). After exposure to PEMF at 0.5, 1, 3, 6, and 12 h, BBB permeability was measured by Evans-Blue extravasation. The expression of occludin, ZO-1, MMP-2, and MMP-9 were detected by real-time quantitative reverse transcriptase PCR and western blotting. MMP-2 and MMP-9 activity were detected by EnzChek gelatinase assay. RESULTS: Compared with the sham group, PEMF exposure led to increased permeability of the BBB to EB, which was prolonged after exposure. BBB permeability became progressively more severe, and recovered at 6 h. The gene and protein expression of occludin and ZO-1 were significantly decreased, while MMP-2 and MMP-9 expression were significantly increased after exposure to PEMF. All levels of expression recovered 12 h following PEMF. CONCLUSION: Changes to BBB permeability were related to the alteration expression of tight junction proteins and matrix metalloproteinase after exposure to PEMF.

[Assessment of external methods of traditional Chinese medicine in patients with chronic ulcer of the lower extremities: study protocol of a multicenter, randomized, parallel-group, prospective trial].

BACKGROUND: Chronic ulcer of the lower extremities amounts for a grave and serious problem for public health. Western medicine focuses on controlling infection, improving blood circulation, surgical debridement, skin grafting, etc, but there are bottlenecks in the treatment. Traditional Chinese medicine (TCM) has a long history and a legacy of sound clinical efficacy in this area. TCM has developed a unique, effective external theory, and a large number of topical prescriptions and external technology. Through this research, a safe and effective treatment protocol of TCM for chronic ulcer of the lower extremities can be formed. To this end, during China's "Eleventh Five-Year" Plan, special research committees and projects on TCM external treatments and external technologies were established. This study on ulcer of the lower extremities constitutes one of the major research topics. METHODS AND DESIGN: Clinical information of patients with chronic ulcer of the lower extremities will be first collected in a large, multicenter, epidemiological survey. Concurrently, a large multicenter, randomized, parallel-group, prospective study will be launched based on evidence-based medical principles to evaluate the efficacy and safety of external methods for removing carrion, dissolving stasis, reinforcing deficiency and promoting tissue regeneration. The evaluated indexes will include the wound healing percentage for primary outcome, wound healing time, wound healing rate, time and rate of removal of necrotic tissue, and TCM syndromes for secondary outcomes and routine blood test, routine urine test, liver and kidney function, blood mercury content and finally urine mercury content for adverse events. DISCUSSION: In this trial, the authors will evaluate the efficacy and safety of external methods for removing carrion, dissolving stasis, reinforcing deficiency and promoting tissue regeneration in cases of chronic ulcer of the lower extremities for standardizing external therapy of TCM for treatment of this condition, and establishing the clinical assessment system for TCM. TRIAL REGISTRATION NUMBER: The research program was registered in the Chinese Clinical Trial Registry in both English and Chinese in June 2011. REGISTRATION NUMBER: ChiCTR-TRC-11001365.

Metabolic perturbations of Lolium perenne L. by enrofloxacin: Bioaccumulation and multistage defense system.

Plants are readily exposed to the antibiotics residues in reclaimed water indicating an urgent need to comprehensively analyze their ecotoxicological effects and fate of these emerging contaminants. Here, we unraveled the dissemination of enrofloxacin (ENR) in a pasture grass, Lolium perenne L., and identified multistage defense systems as its adaptation mechanism. Uptaken concentrations of ENR ranged from 1.28 to 246.60 µg g-1 with bioconcentration factors (BCF) upto 15.13, and translocation factors (TF) upto 0.332. The antioxidant enzymatic activities such as superoxide dismutase, peroxidase, and catalase were increased by upto 115%. Further transcriptomics demonstrated that differentially expressed genes (DEGs) involved in glycolysis, tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and glutathione metabolism were significantly up-regulated by 1.56-5.93, 3-7 and 1.04-6.42 times, respectively; whilst, the DEGs in nitrogen and sulfur metabolism pathways were significantly up-regulated by 1.06-5.64 and 2.64-3.54 folds. These processes can supply energy, signaling molecules, and antioxidants for detoxification of ENR in ryegrass. Such results provide understanding into fasting grass adaptability to antibiotics by enhancing the key protective pathways under organic pollutant stresses in environments.

Viperin is required for optimal Th2 responses and T-cell receptor-mediated activation of NF-kappaB and AP-1.

Viperin (virus inhibitory protein, endoplasmic reticulum [ER]-associated, interferon-inducible) has been identified as a highly inducible ER protein that has antiviral activity. Here, we characterized the phenotype of mice deficient in viperin and examined the biological function of viperin in peripheral T-cell activation and differentiation. Splenic CD4(+) T cells deficient in viperin exhibited normal anti-T-cell receptor (TCR)-induced proliferation and IL-2 production, but produced significantly less T helper 2 (Th2) cytokines, including IL-4, IL-5, and IL-13, in association with impaired GATA3 activation, after stimulation with anti-CD3 antibody, which was not restored upon costimulation with anti-CD28. Th2 differentiation of viperin-deficient naive T cells was also impaired in the presence of strong TCR signaling and minimum IL-4, but not under optimal Th2-skewed conditions. In parallel, viperin-deficient T cells showed decreases in NF-kappaB1/p50 and AP-1/JunB DNA binding activities after TCR engagement. Thus, viperin facilitates TCR-mediated GATA-3 activation and optimal Th2 cytokine production by modulating NF-kappaB and AP-1 activities.

[Succinic semialdehyde dehydrogenase deficiency].

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder. This paper reports three cases of SSADH deficiency in infants. The infants developed the symptoms including developmental delay, intellectual disability, hypotonia, hyporeflexia and seizures. The electroencephalogram (EEG) showed background slowing and focal spike discharges in all of 3 patients. Head magnetic resonance imaging (MRI) demonstrated abnormalities in 2 patients, including basal ganglia damage and increased T2-weighted signal in bilateral cerebral peduncles. Urinary organic acid analysis with gas chromatography-mass spectrometry (GC-MS) revealed increased levels of 4-hydroxybutyrate (GHB) in 3 patients. SSADH deficiency was definitely diagnosed based on the clinical manifestations and the results of urinary organic acid analysis in the 3 children. It was concluded that early urine organic acid analysis is essential for children presenting with mental retardation, neuropsychiatric disturbance or epilepsy of unknown etiology.