Concentrations, Sources and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons in Chinese Herbal Medicines.

The determination and evaluation of 16 polycyclic aromatic hydrocarbons (PAHs) in seven Chinese herbal medicines (CHMs) were conducted through a rapid and straightforward extraction and purification method, coupled with GC-MS. A sample-based solid-phase extraction (SPE) pretreatment technique, incorporating isotopic internal standards, was employed for detecting various medicinal parts of CHMs. The assay exhibited linearity within the range of 5 to 500 ng/mL, with linear coefficients (R2) for PAHs exceeding 0.999. The recoveries of spiked standards ranged from 63.37% to 133.12%, with relative standard deviations (RSDs) ranging from 0.75% to 14.54%. The total PAH content varied from 176.906 to 1414.087 µg/kg. Among the 16 PAHs, phenanthrene (Phe) was consistently detected at the highest levels (47.045-168.640 µg/kg). Characteristic ratio analysis indicated that oil, coal, and biomass combustion were the primary sources of PAHs in CHMs. The health risk associated with CHMs was assessed using the lifetime carcinogenic risk approach, revealing potential health risks from the consumption of honeysuckle, while the health risks of consuming Lycium chinense berries were deemed negligible. For the other five CHMs (glycyrrhizae, Coix lacryma, ginseng, lotus seed, seed of Sterculia lychnophora), the health risk from consumption fell within acceptable ranges. Furthermore, sensitivity analyses utilizing Monte Carlo exposure assessment methods identified PAH levels in CHMs as health risk sensitizers. It is crucial to recognize that the consumption of herbal medicines is not a continuous process but entails potential health risks. Hence, the monitoring and risk assessment of PAH residues in CHMs demand careful attention.

Fabrication of highly crystalline covalent organic framework for solid-phase extraction of three dyes from food and water samples.

Herein, a covalent organic framework, which was fabricated at room temperature by using 1,3,5-tris(p-formylphenyl) benzene and 1,3,5-tris(4-aminophenyl)benzene as building blocks, was employed as an adsorbent for solid-phase extraction of dyes including congo red, methyl blue and direct red 80 for the first time. The prepared covalent organic framework was properly characterized by different techniques and the results revealed that it had a uniform spherical structure, high crystallinity, satisfactory surface area, and good thermal stability. Moreover, the adsorption performance of the material was explored by using static and dynamic adsorption experiments and the results indicated that the material showed good adsorption capacities for three dyes with adsorption capacities in the range of 55.25-284.10 mg/g and the adsorption equilibrium can be achieved in 15 min. Further, to achieve the best adsorption effects of the material, the influence parameters such as pH, ionic strength, type of desorption solvent, and the material dosage in the solid-phase extraction column, were optimized in turn. Finally, under optimal conditions, the solid-phase extraction coupled with HPLC was applied to the analysis of dyes in food and water samples. The recoveries of dyes in actual samples were satisfactory, revealing the unique applicability of the material in the sample pretreatment field.

Novel Self-Assembled Micelles With Increased Tumor Penetration and Anti-Tumor Efficiency Against Breast Cancer.

PURPOSE: Recently, docetaxel (DTX) micelles based on retinoic acid derivative surfactants showed lower systemic toxicity and bioequivalence to polysorbate-solubilized docetaxel (Taxotere®) in a phase II clinical study. However, the poor stability of these surfactants in vitro and in vivo led to extremely harsh storage conditions with methanol, and the formed micelles were quickly disintegrated with rapid drug burst release in vivo. To further enhance the stability and accumulation in tumors of DTX micelles, a novel surfactant based on acitretin (ACMeNa) was synthesized and used to prepare DTX micelles to improve anti-tumor efficiency. METHODS: Novel micelle-forming excipients were synthesized, and the micelles were prepared using the thin film hydration technique. The targeting effect in vitro, distribution in the tumor, and its mechanism were observed. Pharmacokinetics and anti-tumor effect were further investigated in rats and tumor-bearing female mice, respectively. RESULTS: The DTX-micelles prepared with ACMeNa (ACM-DTX) exhibited a small size (21.9 ± 0.3 nm), 39% load efficiency, and excellent stability in vitro and in vivo. Long circulation time, sustained and steady accumulation, and strong penetration in the tumor were observed in vivo, contributing to a better anti-tumor effect and lower adverse effects. CONCLUSIONS: The micelles formed by ACMeNa showed a better balance between anti-tumor and adverse effects. It is a promising system for delivering hydrophobic molecules for cancer therapy.

Comparison of AirSeal versus conventional insufflation system for robot-assisted partial nephrectomy: a meta-analysis and systematic review.

A systematic review and meta-analysis were performed to investigate the efficacy of the AirSeal Valveless Trocar Needle Insufflation System in robot-assisted partial nephrectomy (RAPN). The study compared the differences in perioperative outcomes between the AirSeal insufflation group (AIS) and the conventional insufflation group (CIS). A systematic search of databases such as PubMed, Embase, Cochrane library, and Web of science was performed to identify studies reporting perioperative outcomes between the AirSeal insufflation group (AIS) and the conventional insufflation group (CIS) in RAPN. The study protocol is registered with PROSPERO (CRD42024524335). The primary outcome was to compare the incidence of subcutaneous emphysema (SCE) and postoperative pain scores between the two approaches. The review included four studies with 379 patients, 194 in the AIS group and 185 in the CIS group. Baseline characteristics of the two groups were similar in all outcomes. SCE was significantly lower in the AIS group than in the CIS group [(OR) 0.30 (0.16, 0.54), p < 0.001]. Postoperative 12-h pain scores were also significantly lower in the AIS group compared to the CIS group [(WMD) - 0.93 (- 1.67, - 1.09), p = 0.014]. Both groups showed a significant reduction in length of hospitalization [(WMD) - 0.12 (- 0.84, 0.60), p = 0.746], thermal ischemia time [(WMD) 4.72 (- 5.71, 15.15), p = 0.375], amount of lost hemoglobin [(WMD) - 0.19 (- 0.53, 0.15), p = 0.284], pneumothorax [(OR) 0.13 (0.02,1.10), p = 0.062], mediastinal emphysema [(OR) 0.55 (0.20, 1.46), p = 0.230], and 4-h pain score [(WMD) - 0.25 (- 1.16, 0.65), p = 0.584]; no significant differences were observed. The incidence of subcutaneous emphysema SCE and 12-h pain scores were significantly lower in the AIS group compared to the CIS group. The AirSeal system demonstrated similar efficacy and a higher safety profile than the conventional insufflation system in robotic-assisted partial nephrectomy; however, due to the lack of a randomized study on the topic, further data are needed.

Microfluidic-Enabled Assembly of Multicomponent Artificial Organelle for Synergistic Tumor Starvation Therapy.

Artificial organelles (AOs) encapsulating enzymes are engineered to facilitate biocatalytic reactions for exerting therapeutic effects in various diseases. Exploiting the confinement effect, these catalytic properties exhibit significant enhancements without being influenced by the surrounding medium, enabling more efficient cascade reactions. In this study, we present a novel approach for synergistic tumor starvation therapy by developing multicomponent artificial organelles that combine enzymatic oncotherapy with chemotherapy. The construction process involves a microfluidic-based approach that enables the encapsulation of cationic cores containing doxorubicin (DOX), electrostatic adsorption of cascade enzymes, and surface assembly of the protective lipid membrane. Additionally, these multicomponent AOs possess multicompartment structures that enable the separation and sequential release of each component. By coencapsulating enzymes and chemotherapeutic agent DOX within AOs, we achieve enhanced enzymatic cascade reactions (ECR) and improved intrinsic permeability of DOX due to spatial confinement. Furthermore, exceptional therapeutic effects on 4T1 xenograft tumors are observed, demonstrating the feasibility of utilizing AOs as biomimetic implants in living organisms. This innovative approach that combines starvation therapy with chemotherapy using multicompartment AOs represents a promising paradigm in the field of precise cancer therapy.

Carcinogenic and non-carcinogenic health risk assessment of organic compounds and heavy metals in electronic cigarettes.

E-cigarettes are now very popular in the world. Compared to traditional cigarettes, e-cigarettes are often considered safer and healthier. However, their safety remains controversial and requires further research and regulation. In this study, we aimed to understand the possible hazards to humans of four compounds (formaldehyde, acetaldehyde, acrolein, and acetone) and seven heavy metals (arsenic, cadmium, manganese, lead, copper, nickel, and chromium) contained in e-cigarette liquids and aerosols and perform a health risk assessment. We searched PubMed, CNKI, and other databases for relevant literature to obtain data on organic compounds and heavy metals in e-cigarette liquids and aerosols, and conducted acute, chronic, and carcinogenic risk assessments of various chemicals by different exposure routes. This study showed that exposure to four organic compounds and seven heavy metals in e-cigarette aerosols and e-liquids can cause varying levels of health risks in humans through different routes, with the inhalation route posing a higher overall risk than dermal exposure and oral intake. Various chemicals at high exposure doses can produce health risks beyond the acceptable range. E-cigarette designers must improve their products by changing the composition of the e-liquid and controlling the power of the device to reduce the health effects on humans.

Deterministic and Probabilistic Health Risk Assessment of Toxic Metals in the Daily Diets of Residents in Industrial Regions of Northern Ningxia, China.

This study was designed to investigate the toxic metal (aluminum (Al), arsenic (As), chromium (Cr), cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb), and zinc (Zn)) concentrations in drinking water and different foodstuffs meat (pork, beef, and mutton), cereals (rice, flour, corn, millet), beans (cowpeas, tofu), potatoes (potato, sweet potato), solanaceous fruits (pepper, eggplant, bitter gourd, cucumber), vegetables (cabbage, cauliflower, spinach), and fruits (apples, watermelons, pears, grapes)) and then estimate the potential health risks of toxic metal consumption to local residents in industrial regions of northern Ningxia, China. As in drinking water, Cr in meat, Pb in cereals, Pb in beans, As and Pb in potatoes, Pb in solanaceous fruits, Cr and Ni in vegetables, and Ni and Pb in fruits were the most contaminated heavy metals in the corresponding food with over-standard rates of 16.7%, 12.5%, 5.1%, 60%, 50%, 50%, 38.2%, 44.4%, 44.4%, 31.8%, and 31.8%, respectively.The results of the deterministic assessment of health risks showed that the total noncarcinogenic risk value of dietary intake of toxic metals by the local population was 5.6106, indicating that toxic metals pose a high noncarcinogenic risk. The order of the non-carcinogenic risk is HIcereal (1.2104) > HIsolanaceous fruit (0.9134) > HIVegetables (0.8726) > HIFruit (0.8170) > HIMeat (0.7269) > HIDrinking water (0.6139) > HIBeans (0.2991) > HIPotatoes (0.1573). The total carcinogenic health risk from exposure to toxic metals through dietary intake was 9.98 × 10-4, indicating that the total cancer risk value of residents is beyond the acceptable range (10-4) under the current daily dietary exposure and implies a high risk of cancer. The order of the carcinogenic risk is RDrinking water (2.34 × 10-4) > RMeat (2.11 × 10-4) > Rsolanaceous fruit (1.89 × 10-4) > RFruit (1.88 × 10-4) > Rcereal (1.36 × 10-4) > RPotatoes (2.44 × 10-5) > RVegetables (1.51 × 10-5) > RBeans (0). The probabilistic assessment results showed that 98.83% of the population is exposed to severe noncarcinogenic risk and 87.02% is exposed to unacceptable carcinogenic risk. The sensitivity analysis showed that drinking water, local cereals, vegetables, and fruits were the major contributors to health risks. Our results indicated that the daily dietary exposure of residents in industrial regions of northern Ningxia poses a serious threat to human health, and it is suggested that relevant departments should strengthen monitoring and control of the current situation of toxic metal pollution in the environment and continue to pay attention and take measures to reduce the exposure of toxic metals in the diets of residents in this area.

Robot-assisted versus open radical prostatectomy: a systematic review and meta-analysis of prospective studies.

The study aims to synthesize all available prospective comparative studies and reports the latest systematic analysis and updated evidence comparing robot-assisted radical prostatectomy (RARP) with open radical prostatectomy (ORP) for perioperative, functional, and oncological outcomes in patients with clinically localized prostate cancer (PCa). PubMed, Embase, Web of Science, and the Cochrane Library were retrieved up to March 2023. Only randomized controlled trials (RCTs) and prospective comparative studies were included, and weighted mean differences (WMD) and odds ratios (OR) were used to evaluate the pooled results. Twenty-one articles were included in the present meta-analysis. The results indicated that compared to ORP, RARP had longer operative time (OT) (WMD: 51.41 min; 95%CI: 28.33, 74.48; p < 0.0001), reduced blood loss (WMD: -516.59 mL; 95%CI: -578.31, -454.88; p < 0.00001), decreased transfusion rate (OR: 0.23; 95%CI: 0.18, 0.30; p < 0.00001), shorter hospital stay (WMD: -1.59 days; 95%CI: -2.69, -0.49; p = 0.005), fewer overall complications (OR: 0.61; 95%CI: 0.45, 0.83; p = 0.001), and higher nerve sparing rate (OR: 1.64; 95%CI: 1.26, 2.13; p = 0.0003), as well as was more beneficial to postoperative erectile function recovery and biochemical recurrence (BCR). However, no significant disparities were noted in major complications, postoperative urinary continence recovery, or positive surgical margin (PSM) rates. RARP was superior to ORP in terms of hospital stay, blood loss, transfusion rate, complications, nerve sparing, postoperative erectile function recovery, and BCR. It is a safe and effective surgical approach to the treatment of clinically localized PCa.

Sulfuric acid induced-synthesis coupled with ethanol extraction-water precipitation purification method for orange fluorescent carbon dots with dual-emission: Application for methyl blue detection and cell imaging.

In this work, by adjusting the sulfuric acid content in reaction solvent of ethanol, orange fluorescent carbon dots (O-FCDs) with dual-emission wavelength and blue fluorescent carbon dots (B-FCDs) with single-emission wavelength were successfully prepared using 1,3-dihydroxynaphthalene as precursor. Coupling with ethanol extraction-water precipitation purification method, pure O-FCDs and B-FCDs with yields of 9.0 % and 21.3 %, quantum yields (QYs) of 43.0 % and 13.7 % were obtained, respectively. The structures and optical properties of O-FCDs and B-FCDs were investigated by TEM, AFM, Raman, FT-IR, XPS, UV-vis, fluorescence analysis etc. The results revealed that sulfuric acid promoted the carbonization and the oxidation of precursor in the reaction process. In comparison with the B-FCDs, O-FCDs showed narrower lattice spacing and band gap, demonstrating the important role of sulfur-doping in fluorescence tuning. Additionally, O-FCDs showed good sensitivity for methyl blue with a linear response range of 0.05-100 µM (LOD was 20 nM) and the satisfactory results were obtained when O-FCDs were applied to the detection of methyl blue in real fish sample. Moreover, two FCDs showed good biocompatibility and negligible cytotoxicity proved by MTT experiment, while, O-FCDs showed better cell imaging effects than that of B-FCDs. Therefore, the O-FCDs had a broad application prospect as sensing platform in detection of methyl blue and for imaging in biological field.

Creation of a ready-to-use brexpiprazole suspension and the inflammation-mediated pharmacokinetics by intramuscular administration.

Brexpiprazole (BPZ), which is approved for the treatment of schizophrenia and major depressive disorder, has the potential to meet diverse clinical needs. This study aimed to develop a long-acting injectable (LAI) formulation of BPZ that could provide sustained therapeutic benefits. A library of BPZ prodrugs was screened through esterification, and BPZ laurate (BPZL) was identified as an optimal candidate. To achieve stable aqueous suspensions, a pressure- and nozzle size-controlled microfluidization homogenizer was utilized. The pharmacokinetics (PK) profiles, considering dose and particle size modulation, were investigated following a single intramuscular injection in beagles and rats. BPZL treatment resulted in sustained plasma concentrations above the median effective concentration (EC50) for 2 âˆ¼ 3 weeks, without exhibiting an initial burst release. Histological examination of foreign body reaction (FBR) in rats revealed the morphological evolution of an inflammation-mediated drug depot, confirming the sustained release mechanism of BPZL. These findings provide strong support for the further development of a ready-to-use LAI suspension of BPZL, which could potentially enhance treatment outcomes, improve patient adherence, and address the clinical challenges associated with long-term regimens of schizophrenia spectrum disorders (SSD).

Carbonized human hair derived carbon dots for detection of clozapine.

Clozapine (CLZ) is known as the most effective antipsychotic medication for schizophrenia. However, low dosage or over dosage of CLZ is adverse to the treatment of Schizophrenia. Thus, it is necessary to develop effective detection method for CLZ. Recently, due to the advantages such as excellent optical properties, good photobleachability and sensitivity, carbon dots (CDs)-based fluorescent sensors for the detection of target analytes have drawn a great deal of attention. In this work, blue fluorescent CDs (Named as B-CDs) with quantum yield (QY) as high as 38% were obtained by using carbonized human hair as source material through one-step dialysis method for the first time. B-CDs showed obvious graphite-like structure with an average of 1.76 nm, containing abundant functional groups such as -C=O, amino N and C-N on the surface of carbon cores. Optical analysis showed that the B-CDs exhibited excitation-dependent emission property with maximum emission wavelength of 450 nm. Moreover, B-CDs were further applied as a fluorescence sensor to the detection of CLZ. The B-CDs based sensor exhibited a good quenching response by CLZ through the inner filter effect and static quenching mechanism with a limit of detection of 67 ng/mL, which was much lower than the minimal effective concentration in blood (0.35 µg/mL). Finally, to test the practical application value of the developed fluorescence method, the determination of the content of CLZ in tablets and the concentration in blood was carried out. Compared with the results of high-performance liquid chromatography (HPLC) method, it can be found that the constructed fluorescence detection method showed high accuracy and had great application potential in the detection of CLZ. Additionally, the results of cytotoxicity experiment showed that B-CDs had low cytotoxicity, which laid the foundation for the subsequent application of B-CDs in biological systems.

Sulfuric-acid-mediated synthesis strategy for multi-colour aggregation-induced emission fluorescent carbon dots: Application in anti-counterfeiting, information encryption, and rapid cytoplasmic imaging.

Aggregation-induced emission fluorescent carbon dots (AIE-CDs) have applications in the fields of multi-colour anti-counterfeiting, information encryption, and imaging. In this study, four AIE-CDs (B-AIE-CDs, G-AIE-CDs, Y-AIE-CDs, and O-AIE-CDs) with blue, green, yellow, and orange fluorescence at high concentrations were fabricated using crystal violet as a precursor, solutions with different sulfuric acid concentrations as solvents under different temperatures and reaction times for the first time. The structural properties and fluorescence behaviour of the AIE-CDs were investigated. The results revealed that the sulfuric acid concentration had a significant effect on the fluorescence colour of the AIE-CDs because sulfuric acid can affect the degree of carbonisation, the type and content of nitrogen. Moreover, the reaction temperature and time affected the surface-defect state and the degree of carbonisation of the AIE-CDs, which affected the emission wavelength and quantum yield (QY) of the AIE-CDs. Furthermore, to exploit the unique characteristics (polychromatic aggregation fluorescence and acid-sensitive properties) of the obtained-AIE-CDs, anti-counterfeiting and information encryption methodologies (i.e., acid-stimuli-response producing multi-colour fluorescence) were preliminarily developed. Finally, B-AIE-CDs with a high QY of 43.5% were successfully used for rapid cytoplasmic imaging, demonstrating their applicability in biological fields.

A novel hydroxyl-riched covalent organic framework as an advanced adsorbent for the adsorption of anionic azo dyes.

Considering the highly carcinogenic and mutagenic of anionic azo dyes to the environment and humans, the development of high efficiency adsorbent for them are of great significance. In this study, a novel hydroxyl-riched covalent organic framework (denoted as COF-OH), which can act as an advance adsorbent for anionic azo dyes, was fabricated for the first time. The as-prepared COF-OH demonstrated good dispersion in water, remarkable adsorption performances and good selectivity for anionic azo dyes including eriochrome black T, eriochrome blue black R and congo red. The adsorption capacities of them ranged from 90.71 to 229.12 mg g-1, and the extraction efficiencies of them (>75.91%) were much higher than other dyes (e.g. Methylene blue, direct red 80, 1.46%-39.57%). By optimizing the adsorption conditions (adsorbent dosage, adsorption time, pH, and salt concentration) and desorption conditions (desorption solvent, desorption time and desorption frequency), a dispersive micro solid-phase extraction (D-µ-SPE) method was developed. Further, coupled D-µ-SPE with HPLC-PDA analysis, an effective method was fabricated for the extraction and detection of three selected dyes. The method showed good linearity in the range of 0.1-200 µg mL-1 (R2 > 0.9966), low limits of quantification (0.10 µg mL-1-2.00 µg mL-1), low limits of detection (0.03-1.50 µg mL-1) and good precision. Finally, the COF-OH based D-µ-SPE was successfully applied to extract three selected dyes from water samples (recoveries ranged from 73.90 to 104.00%) and congo red from beverages (recoveries ranged from 81.40 to 111.80%). Besides, by using computer simulation, FT-IR and UV-vis analysis, the adsorption mechanisms of COF-OH to three selected dyes were explored preliminarily.

Hydroxyl-riched covalent organic framework for solid-phase microextraction of flavonoids aglycones or their metabolites in mice's plasma: Luteolin and quercetagetin as examples.

Herein, a hydroxyl­riched covalent organic framework (named COF-DES-1) was synthesized using 1,3,5-tris(4-aminophenyl)benzene and 2,5-dihydroxyterephthalaldehyde as building blocks and employed as a coating of solid-phase microextraction (SPME) fiber. Ascribed to the advantages (e.g. suitable pore size and rich functional group characteristics) of coating, the SPME fiber showed good adsorption capacities to flavonoids aglycones including luteolin and quercetagetin, and the maximum adsorption capacities for them were 145.31 µg and 84.75 µg, respectively. Due to the size exclusion property of COF-DES-1, SPME fiber showed good protein exclusion effects on seven selected proteins with high exclusion efficiencies (>93%). Accordingly, an attractive strategy of the combination of COF-DES-1 based SPME fiber and HPLC-MS/MS was proposed for the extraction and determination of luteolin, quercetagetin or their metabolites. The results revealed that the fiber can be effectively applied to extract luteolin and its metabolites, and quercetagetin from mice's palsma. Compared with the traditional protein precipitation methods, the extraction effects of SPME fiber based extraction method were much better, indicating the promising applicability of the fiber for the enrichment of flavonoids aglycones or their metabolites in biological samples.

Preparation of sulphuric acid-mediated N,S-codoped red emissive carbon dots: Applications in food dyes detection, solid-state luminescence and cell imaging.

As diseases such as cardiovascular disease and cancer caused by food problems are more and more frequent, food safety has received great attention. Among them, the safety problem caused by food dyes is more prominent. Thus, it is of great value to develop sensitive detection methods for food dyes. In present study, sulphuric acid-mediated N,S-codoped red emissive carbon dots (namely as R-CDs) had been manufactured by using N-phenyl-o-phenylenediamine as precursor, sulfuric acid as additive for the first time. The structural and fluorescence properties of R-CDs had been systematically studied. The results demonstrated that R-CDs showed uniform spherical morphology and had a graphite-like structure, for which the average diameters size was 5.05 nm. Due to the various functional groups such as hydroxyl, pyridinic N, pyrrolic N and -C-SO4, R-CDs emitted bright red fluorescence. Importantly, because of the interactions between the functional groups of R-CDs with the selected food dyes, three dyes including amaranth, brilliant blue FCF and methylene blue can sensitively quench the fluorescence of R-CDs through IFE and static quenching effects. The linearity ranges of them were separately detected as 0.20 µM -20 µM, 10 nM-1 µM and 60 nM-8 µM. The limits of detection (LODs) of them were 70 nM, 4 nM and 20 nM, respectively. Further, R-CDs was successfully applied to the sensitive detection of three dyes from various food samples. To maximize the fluorescence properties of R-CDs, a R-CDs/PVA composite gel was fabricated to make R-CDs fluoresce in solid state condition. The potential of R-CDs/PVA composite gel for preliminary visualization analysis of three dyes was studied. Finally, ascribed to the low toxicity and good biocompatibility, the potential of R-CDs as probe for cell imaging was explored preliminarily.

Protection of ripasudil, a Rho kinase inhibitor, in lipopolysaccharides-induced acute pneumonia in mice.

Pneumonia is a major cause of morbidity and mortality of infectious diseases, especially in children. Ripasudil (K-115), a selective ROCK inhibitor, is a promising emerging drug against glaucoma, and reported to have anti-inflammatory activity. However, the anti-inflammatory effect of ripasudil still remains unclear in pneumonia. The goal of this study is to investigate the role and the underlying mechanism of ripasudil in pneumonia. BALB/c mice were used to establish an acute pneumonia model of mice by injection of lipopolysaccharide (LPS) intraperitoneally. Ripasudil (0.5 mg, 1 mg, 2 mg) was administrated 1 h before the induction of LPS. The histoligical change of lung tissue was evaluated by hematoxylin-eosin staining and lung wet/dry ratio. Inflammatory cytokines secretion, oxidant-antioxidant factors levels were measured. Cell apoptosis was examined using TNUEL assay. Western blot and qRT-PCR was used to determine gene expressions. Results showed that ripasudil significantly attenuated LPS-induced histological changes, reduced the production of pro-inflammatory cytokines, and alleviated LPS-induced oxidative stress in mice. LPS-induced cell apoptosis and associated protein expression changes were attenuated by ripasudil. Besides, ripasudil reduced the expression of RhoA, and decreased the activity of RhoA/ROCK signaling. Finally, the level of RhoA and eNOS from pneumonia patients exhibited negatively correlated, whereas the level of RhoA was higher while eNOS level was lower than that in the healthy control. The results of the present study indicate that ripasudil attenuate LPS-induced pneumonia in BALB/c mice by ameliorating inflammation, oxidative stress and apoptosis through inhibiting RhoA/ROCK signaling pathway. Ripasudil might be a novel and effective drug for the treatment of pneumonia.

Rapid and effective diagnosis of tuberculosis and rifampicin resistance with Xpert MTB/RIF assay: a meta-analysis.

OBJECTIVES: Xpert MTB/RIF (Cepheid) assay has been introduced for the diagnosis of tuberculosis (TB) and RIF-resistance. The meta-analysis was used to establish the overall accuracy of Xpert MTB/RIF assay for diagnosing TB and RIF-resistance. METHODS: Based on comprehensive searches of the Pubmed and Embase, we identified outcome data from all articles estimating diagnostic accuracy with Xpert MTB/RIF assay. A summary estimation for sensitivity, specificity, diagnostic odds ratios (DOR) and the area under the summary ROC curve (AUC) was calculated by using the bivariate random-effects approach. RESULTS: The meta-analysis included 18 studies (10,224 suspected specimens). The summary estimate was 90.4% (95%CI 89.2%-91.4%) for sensitivity, 98.4% (95%CI 98.0%-98.7%) for specificity and 328.3/0.9822 for DOR/AUC in pulmonary tuberculosis (PTB). The sensitivity, specificity and DOR/AUC of detecting RIF-resistance were 94.1%, 97.0% and 177.8/0.9832, respectively. For extrapulmonary tuberculosis, the overall pooled sensitivity was 80.4% and specificity was 86.1%. The findings in subgroup analysis were as follows: the accuracy of Xpert MTB/RIF assay is higher in smear-positive specimens and the sensitivity of diagnosing PTB in adults was higher than that in children (90.8% versus 74.3%). CONCLUSIONS: TB and RIF-resistance can be rapidly and effectively diagnosed with Xpert MTB/RIF assay.