Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits.

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2-Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2-Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2-Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

Comparing the protective effects of local and remote ischemic preconditioning against ischemia-reperfusion injury in hepatectomy: a systematic review and network meta-analysis.

Background: Local ischemic preconditioning (LIPC) has been proven to be a protective strategy against hepatic ischemia-reperfusion injury (HIRI) during hepatectomy. Growing evidence suggests remote ischemic preconditioning (RIPC) has the potential to reduce liver injury in hepatectomy. Few studies have directly compared the protective effects of these two mechanical preconditioning strategies. Therefore, we performed a network meta-analysis to compare the efficacy of LIPC and RIPC for hepatic injury during liver resection. Methods: We searched Cochrane, PubMed, Embase, and China National Knowledge Infrastructure (CNKI) from the database inception to January 2023. We included studies directly comparing the effectiveness of LIPC and RIPC and those comparing LIPC or RIPC with no-preconditioning in liver resection. Postoperative liver function and surgical events were analyzed. Data were expressed as standardized mean differences (SMDs) or odds ratios (ORs) and analyzed using network meta-analysis with random effects model. Results: Following the screening of 268 citations, we identified 26 eligible randomized clinical trials (RCTs) involving 1,476 participants (LIPC arm: 789, RIPC arm: 859, no-preconditioning arm: 1,072). LIPC and RIPC were superior to no-preconditioning in reducing postoperative serum transaminase levels [aspartate aminotransferase (AST): SMD RIPC versus no-preconditioning: -2.05, 95% confidence interval (CI): -3.39, -0.71; SMD LIPC versus no-preconditioning: -1.10, 95% CI: -2.07, -0.12; alanine aminotransferase (ALT): SMD RIPC versus no-preconditioning: -2.24, 95% CI: -4.15, -0.32; SMD LIPC versus no-preconditioning: -1.32, 95% CI: -2.63, -0.01]. No significant difference was observed between RIPC and LIPC in postoperative liver function and surgical outcomes (AST: SMD RIPC versus LIPC: -0.95, 95% CI: -2.52, 0.62; ALT: SMD RIPC versus LIPC: -0.91, 95% CI: -3.11, 1.28). In addition, the subgroup analysis revealed the potential benefits of RIPC in improving liver function, especially in patients who diagnosed with cirrhosis or underwent major resection. Conclusions: RIPC and LIPC could serve as effective strategies in relieving HIRI during hepatectomy. No significant differences were observed between LIPC and RIPC, however, RIPC may be an easily applicable strategy to relieve liver injury in hepatectomy.

Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features.

Introduction: The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model. Methods: The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained. Results: No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p < 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups. Conclusion: Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.

Clinical Characteristics of Six Patients with Chlamydia psittaci Infection Diagnosed by Metagenomic Next-Generation Sequencing: A Case Series.

The incidence of psittacosis infection has gradually increased in recent years. Metagenomic next-generation sequencing (mNGS) can be used to comprehensively identify the total DNA and RNA content of the microbiome, as well as identify both known and unexpected pathogens within 24 hours. We diagnosed and treated six patients with psittacosis infection using mNGS, two of whom developed severe disease and most of whom presented with pulmonary symptoms. One of the young female patients also presented with irregular vaginal bleeding and myocarditis. Patients with underlying gastric disorders first showed gastrointestinal symptoms, which is a rare manifestation in patients with psittacosis. Older patients with underlying disease usually showed more severe symptoms. However, rare complications can also occur in immunocompetent young people and develop into severe disease. All patients showed significant congestion at bronchial lumen lesions, which may be associated with a severe inflammatory response to mucosal Chlamydia psittaci (C. psittaci) infection. Overall, mNGS is a rapid and effective tool for the clinical diagnosis of psittacosis caused by C. psittaci, and early diagnosis and treatment can prevent psittacosis from developing into a serious illness.

Esketamine increases neurotransmitter releases but simplifies neurotransmitter networks in mouse prefrontal cortex.

General anesthesia induces a profound but reversible unconscious state, which is accompanied by changes in various neurotransmitters in the cortex. Unlike the "brain silencing" effect of γ-aminobutyric acid (GABA) receptor potentiator anesthesia, ketamine anesthesia leads the brain to a paradoxical active state with higher cortical activity, which is manifested as dissociative anesthesia. However, how the overall neurotransmitter network evolves across conscious states after ketamine administration remains unclear. Using in vivo microdialysis, high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, and electroencephalogram (EEG) recording technique, we continuously measured the concentrations of six neurotransmitters and the EEG signals during anesthesia with esketamine, an S-enantiomer of ketamine racemate. We found that there was an increase in the release of five cortical neurotransmitters after the administration of esketamine. The correlation of cortical neurotransmitters was dynamically simplified along with behavioral changes until full recovery after anesthesia. The esketamine-increased gamma oscillation power was positively correlated only with the concentration of 5-hydroxytryptamine (5-HT) in the medial prefrontal cortex. This study suggests that the transformation of the neurotransmitter network rather than the concentrations of neurotransmitters could be more indicative of the consciousness shift during esketamine anesthesia.NEW & NOTEWORTHY In this study, we found that esketamine significantly increased the cortical concentration of multiple neurotransmitters in mice. However, esketamine dynamically simplified the overall network of cortical neurotransmitters at different behavioral states during the perianesthesia period. The concentration of 5-HT in the medial prefrontal cortex (mPFC) was highly correlated with the esketamine-increased gamma oscillation. These findings suggested that the transformation of the neurotransmitter network rather than the concentrations of neurotransmitters could be more indicative of the consciousness shift during esketamine anesthesia.

Prospects of Inhaled Phage Therapy for Combatting Pulmonary Infections.

With respiratory infections accounting for significant morbidity and mortality, the issue of antibiotic resistance has added to the gravity of the situation. Treatment of pulmonary infections (bacterial pneumonia, cystic fibrosis-associated bacterial infections, tuberculosis) is more challenging with the involvement of multi-drug resistant bacterial strains, which act as etiological agents. Furthermore, with the dearth of new antibiotics available and old antibiotics losing efficacy, it is prudent to switch to non-antibiotic approaches to fight this battle. Phage therapy represents one such approach that has proven effective against a range of bacterial pathogens including drug resistant strains. Inhaled phage therapy encompasses the use of stable phage preparations given via aerosol delivery. This therapy can be used as an adjunct treatment option in both prophylactic and therapeutic modes. In the present review, we first highlight the role and action of phages against pulmonary pathogens, followed by delineating the different methods of delivery of inhaled phage therapy with evidence of success. The review aims to focus on recent advances and developments in improving the final success and outcome of pulmonary phage therapy. It details the use of electrospray for targeted delivery, advances in nebulization techniques, individualized controlled inhalation with software control, and liposome-encapsulated nebulized phages to take pulmonary phage delivery to the next level. The review expands knowledge on the pulmonary delivery of phages and the advances that have been made for improved outcomes in the treatment of respiratory infections.

Clinical study of invasive pulmonary aspergillosis following influenza A H1N1.

ABSTRACT: This study to analyze the clinical characteristics of patients with invasive pulmonary aspergillosis (IPA) following influenza A (H1N1) infection.We retrospectively analyzed 10 cases with IPA following H1N1 infection. The clinical manifestations, laboratory examination results, chest computed tomography, and treatments were analyzed.Clinical manifestations: all 10 cases had typical flu-like symptoms at the onset of the disease, among which 7 patients developed dyspnea in the late stage, and 8 patients had hemoptysis. Laboratory examination: the absolute and percentage of peripheral blood lymphocytes in all 10 patients were declined, among which 5 cases were with decreased CD3+ CD4+ T cells/lymphocytes; 9 cases with increased bronchoalveolar lavage fluid galactomannan; 6 cases with increased serum galactomannan; 1 case with bronchoalveolar lavage fluid cultured aspergillus fumigatus; and 2 cases with aspergillus by second-generation sequencing. Chest computed tomography: all patients showed multiple diffused ground-glass opacities at the beginning, along with linear or reticular interstitial changes. Two cases had multiple subarachnoid nodules with halo signs, 3 cases had consolidation in multiple segments of both lungs, 2 cases had cavities, and 4 cases were with pleural effusion. Treatment: 10 patients were treated with antiviral and anti-Aspergillus drugs after admission. Four patients received respiratory support. All 10 cases were cured and discharged.Early diagnosis of IPA in influenza A (H1N1) patients is the key to successful treatment.

Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia.

AIMS: General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating. METHODS: Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst-suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods. RESULTS: We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5-HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5-HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons. CONCLUSION: Our results demonstrate that 5-HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5-HT 1A and 2C receptors.

Prevalence and determinants of potentially inappropriate medications prescribing in elderly patients in Chinese communities.

BACKGROUND: To assess the prevalence and associated risk of potentially inappropriate medications (PIMs) prescribing in community-dwelling elderly patients in China and to examine the most frequently used PIMs. This will provide a reference for the formulation of medication manuals for the community-dwelling elderly and further standardize the use of medications in elderly patients. METHODS: We conducted a cross-sectional retrospective study from April 1, 2020 to April 30, 2020. Data from elderly patients aged ≥65 years were collected from the Hengjie (N=2,294), Loujiang (N=3,972), and Tongxing communities (N=1,969) in Suzhou. The frequency of PIMs was detected using the 2019 Beers criteria and the 2017 Chinese criteria. Chi-square (for categorical variables), ANOVA (for continuous variables as applicable), and logistic regression were used to describe and identify potential predictors of PIMs. RESULTS: A total of 8,235 elderly patients were examined. Using the Chinese criteria, the prevalence of PIMs was 37.07%, which was slightly higher than that found using the 2019 Beers criteria (32.16%). The most prescribed PIMs were estazolam (21.53%) and insulin (4.60%) based on the Chinese criteria. Logistic regression analysis showed that advanced age, polypharmacy, and comorbid disease of patients were associated with a high risk of PIMs. Furthermore, the educational background and professional title of physicians were also associated with PIMs. CONCLUSIONS: Given the high prevalence of PIMs in the Chinese community-dwelling elderly population, the implementation of evidence-based interventions to promote rational clinical drug use could improve their quality of life.

Regulatory roles of HSPA6 in Actinidia chinensis Planch. root extract (acRoots)-inhibited lung cancer proliferation.

Actinidia chinensis Planch. root extract (acRoots) as one of Chinese traditional medications has been applied for antitumor therapy for decades, although the exact mechanisms have not been revealed. Our present study aimed to define the inhibitory specificity and pattern of acRoots in the lung cancer cell lines by comparing 40 types of cancer cell lines, select acRoots-associated inflammation target genes from transcriptional profiles of acRoots-sensitive and less-sensitive lung cancer cell lines, and validate the correlation of acRoots-associated inflammation target genes with prognosis of patients with lung cancer. We selected acRoots-sensitive (H1299) and less-sensitive lung cancer cells (H460) and found that the sensitivity was associated with the appearance of p53. The heat shock 70 kDa protein 6 (HSPA6) was defined as a critical factor in regulating cell sensitivity probably through the interaction with intra-HSPA family members, inter-HSP family members, and other families. The degree of cell sensitivity to acRoots increased in both sensitive and less-sensitive cells after deletion of HSPA6 genes. Thus, our data indicate that HSPA6 and HSPA6-dominated molecular network can be an alternative to modify cell sensitivity to drugs.

Surgical management of Sprengel's deformity by a modification of Green's procedure : A single center experience.

BACKGROUND: Sprengel's deformity is a rare congenital anomaly that can present in children, leading to cosmetic and functional impairment. This study investigated clinical results of this deformity among cases managed using a modified Green procedure. METHODS: From February 2008 to September 2015 a total of 34 patients with Sprengel's deformity were treated with a modified Green procedure. The mean age of patients at the time of surgery was 4.8 years (range 2-12 years) and the average follow-up time was 6.1 years (range 4-10 years). The shoulder abduction, Cavendish classification, Rigault classification, scapular elevation, and postoperative complications were evaluated. RESULTS: The mean shoulder abduction was 102.3° (range 70-140°) preoperatively and 142.6° (range 120-170°) postoperatively. The scapular elevation was 4.2 cm (range 2-6.5 cm) preoperatively and 1.35 cm (range 0-2 cm) postoperatively. Improvement by at least one Cavendish and/or Rigault grade was attained in all cases postoperatively. The differences in preoperative and postoperative shoulder abduction, scapular elevation, Cavendish grade and Rigault grade were statistically significant (p < 0.001). CONCLUSION: The modified Green procedure is a relatively safe and reliable method in the treatment of severe Sprengel's deformity, which ensures successful shoulder function as well as a good cosmetic appearance.

Local Delivery of Silk-Cellulose Incorporated with Stromal Cell-Derived Factor-1α Functionally Improves the Uterus Repair.

Severe infection and mechanical injury of the uterus may lead to infertility and miscarriage. Currently, there is a lack of effective treatment modality for functional repair of uterine injury. To address this clinical challenge, this study aimed to develop a chemotactic composite scaffold by incorporating recombinant human stromal cell-derived factor-1α (rhSDF-1α) into a silk fibroin-bacterial cellulose (SF-BC) membrane carrier. A rat model of uterine injury was utilized for this study, which was composed of three groups as follows: blank control, implantation with SF-BC only, or SF-BC loaded with rhSDF-1α. The tissue regeneration efficacy of the three groups was analyzed and compared. The results showed that SF-BC loaded with rhSDF-1α significantly enhanced endometrial regeneration and arteriogenesis of the injured rat uterus, which led to improved pregnancy outcomes, thus indicating much promise for functional uterine repair and regeneration. Impact Statement In this study, we demonstrated that the silk fibroin-bacterial cellulose (SF-BC) membrane possessed good physical, chemical, and biocompatibility properties in vitro. The in vivo study showed that the incorporation of recombinant human stromal cell-derived factor-1α (rhSDF-1α) within the SF-BC membrane promoted regeneration of full-thickness uterine injury and also improved the pregnancy outcome of the damaged uterus. The results thus suggest that SF-BC loaded with rhSDF-1α has good potential in future clinical applications for the repair of uterine injury.

High-Strength, Durable All-Silk Fibroin Hydrogels with Versatile Processability toward Multifunctional Applications.

Hydrogels have been the focus of extensive research due to their potential use in fields including biomedical, pharmaceutical, biosensors, and cosmetics. However, the general weak mechanical properties of hydrogels limit their utility. Here, we generate pristine silk fibroin (SF) hydrogels with excellent mechanical properties via a binary solvent induced conformation transition (BSICT) strategy. In this method, the conformational transition of SF is regulated by moderate binary solvent diffusion and SF/solvent interactions. ß-sheet formation serves as the physical crosslinks that connect disparate protein chains to form continuous 3D hydrogel networks, avoiding complex chemical and/or physical treatments. The Young's modulus of these new BSICT-silk fibroin hydrogels can reach up to 6.5±0.2 MPa, tens to hundreds of times higher than that of conventional hydrogels (0.01-0.1 MPa). These new materials filled the "empty soft materials space" in the elastic modulus/strain Ashby plot. More remarkably, the BSICT-SF hydrogels can be processed into different constructions through different polymer and/or metal based processing techniques, such as molding, laser cutting, and machining. Thus, these new hydrogel systems exhibit potential utility in many biomedical and engineering fields.

Is Mitochondrial Cell Fragility a Cell Weakness?

Mitochondrial dysfunction has historically been linked to the cessation of cell function and ageing. Downstream effects such as reduced calcium buffering capacity, elevated levels of reactive oxygen species, and alterations in adenosine-5'-triphosphate are linked to a wide variety of pathological diseases. The importance of the mitochondria has increasingly been highlighted due to its potential as a therapeutic target for drug intervention and cell elimination in cancer. In addition, due to its origin, drugs targeting bacteria are required to be thoroughly tested prior to administration to prevent toxicity for the mitochondria. In this chapter, we will discuss a variety of factors that could influence mitochondrial dysfunction and highlight potential solutions to these. A comprehensive understanding regarding the mechanisms underlying mitochondrial dysfunction could aid in developing future therapeutic targets in multiple pathologies such as cancer and liver diseases.

Pinocembrin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice.

Pinocembrin, one of the primary flavonoids in propolis, possesses many biological activities, including anti-inflammation, anti-oxidation and immunoregulation. This study aimed to evaluate whether pinocembrin could attenuate ovalbumin (OVA)-induced allergic airway inflammation in mice and to explore the possible mechanism. BALB/c mice sensitized and challenged with OVA were administered intraperitoneally with pinocembrin. Airway inflammation and airway hyperresponsiveness were examined. T-helper type (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) and OVA-specific immunoglobulin E (IgE) in serum were determined. The activation of nuclear factor kappa B (NF-κB) p65 were also measured. Our results showed that pinocembrin resulted in significant inhibition of pathophysiological signs of allergic asthma, including increased pulmonary eosinophilia infiltration, mucus hypersecretion and airway hyperresponsiveness (AHR). Treatment with pinocembrin significantly reduced Th2 cytokines interleukin (IL)-4, IL-5 and IL-13 in BALF, and OVA-specific IgE in serum. Moreover, pinocembrin treatment suppressed phosphorylation of inhibitor-κBα (IκBα) and NF-κB subunit p65 activation in lung tissue of OVA-sensitized mice. These data suggest that pinocembrin may inhibit allergic airway inflammation, and providing potential benefits in the treatment of inflammatory disease.

Peroxisome proliferator-activated receptor γ agonist suppresses mast cell maturation and induces apoptosis.

Peroxisome proliferator-activated receptor gamma (PPAR Î³), is important in the immunoregulation of the allergic response. Mast cells are the most important inflammatory cells in immediate hypersensitivity and allergic diseases. However, there is limited information regarding the effects of PPAR Î³ on mast cell maturation. In the present study, mouse bone marrow­derived mast cells (BMMCs) were cultured in interleukin (IL)­3 and stem cell factor (SCF), in the presence or absence of the PPAR Î³ agonist, pioglitazone (PIO). The expression levels of the tyrosine kinase receptor CD117 and the high affinity IgE receptor FcεRI α, were assessed by flow cytometry, cell viability was assessed by Alamar­Blue assay and histamine release was determined by measuring the activity of ß­hexosaminidase. IL­3 and SCF are required for the development of mast cells in vitro. PIO dose­dependently inhibited the expression of CD117 and FcεRI α, and the maturation of BMMCs. Treatment with PIO additionally inhibited the formation of granules and reduced the expression of ß­hexosaminidase. In addition, reverse transcription­polymerase chain reaction analysis revealed that BMMCs treated with PIO expressed a lower level of mast cell protease (MCP)­6 mRNA and PIO treatment enhanced the level of PPAR Î³ mRNA. Furthermore, PIO induced mast cell progenitor apoptosis. PPAR Î³ agonists may maintain mast cell homeostasis by inhibiting maturation of their precursors. The inhibitory effects of PPAR Î³ agonists include suppression of the activation of mast cells and a decrease in mast cell function in the inflammatory response. Therefore, PPAR Î³ agonists may serve as effective anti-inflammatory reagents in the treatment of allergic reactions.

Response surface modeling-based source contribution analysis and VOC emission control policy assessment in a typical ozone-polluted urban Shunde, China.

To develop a sound ozone (O3) pollution control strategy, it is important to well understand and characterize the source contribution due to the complex chemical and physical formation processes of O3. Using the "Shunde" city as a pilot summer case study, we apply an innovative response surface modeling (RSM) methodology based on the Community Multi-Scale Air Quality (CMAQ) modeling simulations to identify the O3 regime and provide dynamic analysis of the precursor contributions to effectively assess the O3 impacts of volatile organic compound (VOC) control strategy. Our results show that Shunde is a typical VOC-limited urban O3 polluted city. The "Jiangmen" city, as the main upper wind area during July 2014, its VOCs and nitrogen oxides (NOx) emissions make up the largest contribution (9.06%). On the contrary, the contribution from local (Shunde) emission is lowest (6.35%) among the seven neighbor regions. The local VOCs industrial source emission has the largest contribution comparing to other precursor emission sectors in Shunde. The results of dynamic source contribution analysis further show that the local NOx control could slightly increase the ground O3 under low (10.00%) and medium (40.00%) reduction ratios, while it could start to turn positive to decrease ground O3 under the high NOx abatement ratio (75.00%). The real-time assessment of O3 impacts from VOCs control strategies in Pearl River Delta (PRD) shows that the joint regional VOCs emission control policy will effectively reduce the ground O3 concentration in Shunde.

Evaluation of Neck Lymph Node Metastasis on Contrast-Enhanced Ultrasound: An Animal Study.

OBJECTIVES: To assess the performance of contrast-enhanced ultrasound (CEUS) intended to differentiate hyperplastic from malignant neck lymph nodes in an animal model. METHODS: Twenty-four New Zealand rabbits were randomly divided into two groups: neck lymph node metastasis group (12 rabbits) and reactive hyperplastic lymph node group (12 rabbits). Tongue VX2 carcinoma with cervical lymph node metastasis was induced in 12 rabbits by injecting VX2 carcinoma suspension into the left tongue submucosa. Hyperplastic neck lymph nodes were induced by injecting egg yolk in the submandibular region of the rabbits in hyperplastic group. CEUS were performed in both groups before and after intravenous administration of SonoVue. The site, number, echogenicity, longitudinal and transverse nodal dimensions, patterns of enhancement of the neck lymph nodes were observed and recorded. RESULTS: In both groups only one lymph node was found in the left (tumor) side of the neck. CEUS found 12 of 12 metastatic lymph nodes in metastasis group, and diagnosed 11 of 12 lymph nodes as metastatic. Histopathologic analysis revealed metastatic lesions in all 12 rabbits, each with one lymph node, and all 12 lymph nodes in hyperplastic group is inflammation lymph nodes. All 12 cases in the hyperplastic group showed centripetal homogeneous enhancement while in the metastasis group one case showed centripetal homogeneous enhancement, three cases showed centrifugal heterogeneous enhancement, and eight cases showed diffused heterogeneous enhancement. Only one lymph node was dissected on the left side of the neck in each rabbit in both groups. CONCLUSION: CEUS can play a role in discriminating metastatic from hyperplastic lymph nodes in head and neck carcinoma.

Exome sequencing identifies a mutation in TMC1 as a novel cause of autosomal recessive nonsyndromic hearing loss.

BACKGROUND: Autosomal recessive non-syndromic hearing loss (ARNSHL) is highly heterogeneous, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) have been implicated in its development. To date, 35 homozygous mutations in TMC1, identified in over 60 families worldwide, have been shown to be associated with ARNSHL. However, few of these mutations were detected in the Chinese population. In this study, we describe a pathogenic missense mutation located in the T5-T6 domain of TMC1 in a three-generation Chinese family with 14 members. METHODS: Whole exome sequencing was performed using samples from one unaffected individual and two affected individuals to systematically search for deafness susceptibility genes. Candidate mutations and cosegregation of the phenotype were verified by polymerase chain reaction and Sanger sequencing in all of the family members. RESULTS: We identified a novel TMC1 mutation in exon 20, c.1979C>T, p.P660L, which segregated with prelingual autosomal recessive sensorineural hearing loss. CONCLUSIONS: We found a new missense mutation in the T5-T6 domain of TMC1, which is highly conserved in many species. These data support the potential conserved role of p.P660L in human TMC1 function.