[The cases of tracing the source of patients infected with Omicron variant of SARS-CoV-2 based on wastewater-based epidemiology in Shenzhen].

Wastewater-based epidemiology (WBE) is an emerging discipline, which has been applied to drug abuse tracking and infectious disease pathogen surveillance. During the COVID-19 epidemic, WBE has been applied to monitor the epidemic trend and SARS-CoV-2 variants etc. In order to detect hidden COVID-19 cases and prevent transmission in the community, wastewater surveillance system for monitoring SARS-CoV-2 RNA was developed in Shenzhen. The sewage sampling sites were set up in key places such as the port areas, urban villages and residential communities of Futian, Nanshan, Luohu and Yantian districts. From July 26 to November 30, 2022, a total of 369 sewage sampling sites were set up, covering 1.93 million people. Continuous sampling was carried out for 3 hours in the peak period of water use every day. Sewage virus enrichment and SARS-CoV-2 nucleic acid detection were carried out by polyethylene glycol precipitation method and RT-qPCR, and a positive water sample disposal process was molded. This article aims to introduce the case of source tracing of COVID-19 infected patients based on urban sewage in Shenzhen. The sewage monitoring of Honghu water treatment plant in Luohu District played an early warning role, and the source of infection was traced. In the disposal of positive water samples in Futian South Road, Futian District, the important experience of monitoring point layout was obtained. In the sewage monitoring of Nanshan village, Nanshan District, the existence of occult infection was revealed. Sharing the experience of tracing the source of COVID-19 patients to avoid the spread of COVID-19 in the community based on wastewater surveillance of SARS-CoV-2 RNA in Shenzhen, and summarizing the advantages and application prospects of sewage surveillance can provide new ideas for monitoring emerging or re-emerging pathogens that are known to exhibit gastrointestinal excretion in the future.

[Analysis of the risk factors for poor prognosis and recurrence in patients with anti-NMDAR encephalitis].

To investigate the risk factors of poor prognosis and recurrence in patients with anti-NMDAR encephalitis. A single center, observational cohort study was used to retrospectively analyze 44 patients with anti NMDAR encephalitis hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from January 2014 to October 2020. The results showed that the interval from onset to immunotherapy in the poor prognosis group was significantly longer than that in the good prognosis group (t=2.045,P=0.047), and the course of disease in the poor prognosis group was significantly longer than that in the good prognosis group (t=4.127,P=0.000 2). The number of patients with clinical manifestations of dyskinesia was significantly increased (Fisher exact test: P=0.014). The patients with abnormal brain MRI in the poor prognosis group were significantly more than those in the good prognosis group (Fisher exact test: P=0.017), and the patients with slow wave>50% in the poor prognosis group were significantly more than those with slow wave <50% (Fisher exact test: P<0.001). Patients with the first onset of immunotherapy time <3 months, long course of disease, high intracranial pressure, and high cerebrospinal fluid protein are prone to relapse. Bivariate logistic regression analysis showed that patients with dyskinesia, abnormal brain MRI, and slow wave EEG more than 50% were risk factors for poor prognosis (OR values were 4.687, 4.978, and 24.500, respectively; P values were 0.018, 0.016, and 0.000, respectively). The time of first-line immunotherapy for the first onset<3 months was the risk factor for recurrence (OR 17.231, P=0.010). In conclusion, dyskinesia, abnormal brain MRI and slow wave of EEG more than 50% may be the risk factors for poor prognosis of patients. The duration of immunotherapy less than 3 months after the first onset might be the risk factor for recurrence.

[Exploration and practice of artificial intelligence assisted primary vision health management].

It has attracted much attention worldwide that the application of artificial intelligence (AI) in primary screening and clinical diagnosis and treatment of eye diseases. In recent years, this technology has also been widely used in various grass-roots eye disease management, effectively improving the current situation of weak eye disease diagnosis ability and shortage of human resources in primary medical institutions. At present, there is no reference standard or guideline for the management mode, implementation content and management method of vision health management based on this technology, which are in urgent need of standardization. The article described the work mode exploration of AI-assisted grass-roots visual health management in Shanghai and shared practical experience. The aim is to provide reference for other provinces in China to carry out relevant work.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

[Three dimensional nephrometry system for partial nephrectomy: Our initial exploration].

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm3 and (33.0±36.4) cm3, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION: Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.

[Digital and anatomical study of posterior atlantooccipital joint-occipital condyle-clivus screw technique].

Objective: To investigate the screw placement parameters, feasibility and safety of posterior atlantooccipital joint-occipital condyle-clivus screw technique in Chinese people. Methods: Upper cervical spine CT images of 46 patients, including 24 males and 22 females, were collected with random number table from June 2019 to May 2020 in Ningbo No.6 Hospital. The patients aged 20-55 years, with a mean age of (39±9) years. Total of 92 sides of upper cervical spine models were obtained by Mimics 19.0 digital three-dimensional reconstruction, and screw placement was conducted simulately. The midpoint of transition zone between the posterior arch of atlas and the inferior articular process of lateral mass was selected as the screw entry point. The diameter and length of screws was 3.5 mm and 50 mm, respectively. Detailed morphometric measurements of the 92 atlantooccipital joint-occipital condyle-clivus screws were conducted. The distance between the screw and its surrounding important structures, screw inside and upper tilting angles, the length of screw trajectory in atlas and the length of screw trajectory on occipital side (occipital condyle-clivus) were all measured. Paired t test was performed on the parameters of left and right screw placement to confirm whether there was difference between the two sides. Results: In the 46 cases of upper cervical spine digital three-dimensional models, 92 posterior atlantooccipital joint-occipital condyle-clivus screws were implanted. All the screws were completely fixed in the clivus, without breaking through the upper sphenoid sinus, entering into the canalis spinalis and foramen magnum, and damaging the surrounding structures such as hypoglossal canal. The screw trajectory parameters between the left and right sides were slightly different, but there was no statistical differences between the two sides (P>0.05). The vertical distance between the screw entry point and the upper edge of atlas was (12.6±1.0) mm, the vertical distance between the screw entry point and the lower edge of atlas was (6.5±0.6) mm, the distance between the screw and the medial border of atlas vertebral artery foramen was (6.7±0.6) mm, the distance between the screw entry point and the medial wall of atlas was (6.6±0.7) mm, the distance between the screw outer margin and the hypoglossal canal was (5.5±0.6) mm, screw inside tilting angle was 21.2°±2.5°, screw upper tilting angle was 52.0°±3.4°, the length of screw trajectory in atlas was (12.1±0.9) mm, the length of screw trajectory on occipital side (occipital condyle-clivus) was (37.9±0.9) mm. Conclusion: The posterior atlantooccipital joint-occipital condyle-clivus screw technique can serve as a feasible and safe treatment for instability of the occipitocervical junction, which can be used as a new posterior occipitocervical fusion technique.

[Biomechanical study of anterior occipital condyle screw plate system].

Objective: To analyze the feasibility of anterior occipitocervical fusion biomechanical characteristic of craniovertebral reconstruction by anterior occipital condyle screw plate system. Methods: Six cervical vertebra specimens including 4 males and 2 females were enrolled, whose mean age of death was (49.3±7.5) years. The normal models were established by soft tissue dissection, and the instability models were established by destroy bone and ligament structure including, anterior arch of the atlas, part of the lateral mass of the atlas, the odontoid process, the odontoid apical ligament, the pterygoid ligament, the transverse ligament of the atlas the joint capsule. The clivus screw fixation models were established by anterior clivus screw fixation, and then those models were performed by anterior occipital condyle screw fixation. All four groups were loaded with a 1.5 N·m continuous pure force in flexion-extension, lateral bending, and axial rotation. Then measured the range of motion of specimen C0-C1 and C0-C2. And the pull-out force test was conducted to compare the effects of unicortical and bicortical fixation on the pull-out force of screws. Results: In the C0-C1 segment, the range of motion in flexion-extension (forward and posterior), lateral bending and axial rotation in the clivus group was 6.46°±0.85°, 5.14°±0.76°, 2.73°±0.36°, 1.12°±0.41°, respectively; and it was 5.92°±0.90°, 4.16°±1.06°, 2.86°±0.50°, 1.05°±0.27°, respectively in the occipital condyle group. As for C0-C2 segment, the range of motion in the clivus group was 9.55°±1.99°, 10.46°±2.03°, 6.90°±1.29°, 13.51°±1.37°, respectively; and it was 8.14°±1.38°, 9.53°±1.55°, 4.75°±1.06°, 7.90°±1.68°, respectively, in the occipital condyle group. The ranges of motion in the occipital condyle group were significantly lower than clivus group (all P<0.05). The maximum pull out force by bicortical fixation was significantly better than unicortical fixation ((439±33) N vs (408±28) N, P<0.05). Conclusion: The anterior occipital condyle screw plate system provides better stability especially in anti-bending and anti-rotation than the anterior clival screw fixation.

[Study on the correlation between subgroup of blood lipid with degree of coronary artery stenosis in patients with coronary atherosclerotic heart disease].

Objective: To study the correlation between low-density lipoprotein particles (LDL-P) with other lipoprotein indexes. To explore the correlation between LDL-P and its subgroup particles(LDL1-P-LDL6-P) with the degree of coronary artery stenosis in patients with coronary atherosclerotic heart disease(CHD) combining with the result of coronary arteriography. To explore the value of lipoprotein subgroup granules in preventing the severity of coronary artery stenosis in CHD patients. Methods: Cross-sectional study. A total of 259 patients without lipid-lowering drugs for coronary angiography in the department of cardiology of TEDA International Cardiovascular Hospital during 3 months from August 2019 to December 2019 were collected, and 52 healthy subjects were recruited during the same period. The level of high sensitivity C-reactive protein (hs-CRP) and other biochemical indexes were detected by automatic biochemical analyzer. The level of LDL-P and other biochemical indexes were detected by nuclear magnetic resonance spectroscopy(NMRS). The relation between various biomarkers levels with coronary artery stenosis degree was analyzed. Analysis of variance and nonparametric tests were used to compare the differences of indexes among each group. Pearson correlation analysis was used to determine the correlation among the measured indexes. Logistic regression was used for multi-factor analysis, ROC curve was used to evaluate the diagnostic value of related indexes. Results: LDL-P was highly correlated with low-density lipoprotein cholesterol (LDL-C),apolipoprotein B (ApoB) and total cholesterol (TC) (r= 0.927, P<0.001; r=0.921, P<0.001; r=0.844, P<0.001). LDL-P, LDL4-P, LDL5-P and LDL6-P in patients with severe coronary stenosis were higher than those in patients with mild coronary stenosis(U=4 172.000, Z=4.256, P<0.001; t=2.573, P=0.011; U=3 995.000, Z=4.621, P<0.001;t=5.223, P<0.001), LDL-P and LDL6-P were higher than those of patients with moderate coronary stenosis (U=1 159.000, Z=2.294, P=0.022; t=2.075, P=0.041). High levels of hs-CRP, LDL5-P and LDL6-P were risk factors for the degree of coronary stenosis(OR=1.095, P=0.036;OR=1.015, P=0.046;OR=1.012, P=0.039). ROC analysis showed that the AUC of LDL-P, LDL5-P and LDL6-P on coronary stenosis was 0.67, 0.68 and 0.69, respectively. Hs-CRP combined with LDL5-P and LDL6-P had the greatest effect on the degree of coronary stenosis (AUC= 0.70). Conclusions: LDL-P is highly correlated with LDL-C. The levels of LDL-P and LDL6-P were significantly higher in patients with severe stenosis than in patients with mild and moderate stenosis. hs-CRP, LDL5-P and LDL6-P can be used as new risk factors for the degree of coronary stenosis and may be further used as risk predictors. The combined detection of hs-CRP, LDL5-P and LDL6-P is helpful for the diagnosis of the severity of coronary stenosis, and may further become risk predictors.

Mitochondrial fission is necessary for mitophagy, development and virulence of the insect pathogenic fungus Beauveria bassiana.

AIMS: Mitochondrial fission is an essential dynamics that maintains mitochondrial morphology and function. This study seeks to determine the roles of mitochondrial fission in the filamentous entomopathogenic fungus Beauveria bassiana. MATERIAL AND METHODS: Three fission-related genes (BbFis1, BbMdv1 and BbDnm1) were functionally characterized via protein intracellular localization and construction of gene disruption mutants. RESULTS: Mitochondrial localization was only observed for BbFis1 which interacts with BbMdv1, but BbMdv1 did not have interaction with BbDnm1. Single disruption mutant of three genes generated the elongated and enlarged mitochondria which could not be eliminated via the mitophagy. Three mutant strains displayed the reduced ATP synthesis and vegetative growth compared with the wild type. Three genes were involved in the early stage of conidiation and unnecessary for the late stage. However, all three genes significantly contribute to blastospore development under submerged condition, and the loss of BbMdv1 had the greatest effects compared with the losses of BbFis1 or BbDnm1. Finally, disruption of three genes significantly attenuated fungal virulence, but their mutations had different influences. CONCLUSIONS: In addition to their consistent roles in mitochondrial division and mitophagy, three fission-related genes perform divergent roles in the development and virulence of the entomopathogenic fungus B. bassiana. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that mitochondrial fission is associated with lifecycle of B. bassiana. These findings provide information for the manipulation of fungal physiology and facilitate the application of entomopathogenic fungi.

[The association of lipid profile and bleeding in patients with minor stroke or transient ischemic attack on antiplatelet therapy: subgroup analysis of CHANCE].

Objective: Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods: Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3 044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results: A total of 59 (1.9%) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95%CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04; 95%CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05; 95%CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions: Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.

Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is characterized by metabolic disturbances in calcium and phosphorus homeostasis as kidney function declines. Alterations in blood perfusion in bone resulting from arteriosclerosis of bone vessels may relate to the progression of CKD. Herein, change in dynamic contrast enhanced (DCE) MRI parameters (A: amplitude, kel: elimination constant, and kep: permeability rate constant) and MRI T2∗ relaxation time of the knee cartilage were measured in a rodent nephrectomy model in order to (1) examine the relationship of peripheral blood perfusion to CKD and (2) demonstrate the feasibility of using DCE-MRI parameters and MRI T2∗ as imaging biomarkers to monitor disease progression. DESIGN: Two groups of male Sprague-Dawley rats received either (1) no intervention or (2) 5/6 nephrectomy. RESULTS: We found that the CKD group (compared with the control group) had lower A and kel values and similar kep value in the lateral and medial articular cartilages beginning at 12 weeks (P < 0.05); statistically significantly higher T2∗ values in the lateral and medial articular cartilages beginning at 18 weeks (P < 0.05); statistically significantly decreased inner luminal diameter of the popliteal artery, and altered structure of the lateral and medial articular cartilages (P < 0.05). CONCLUSION: Perfusion deficiency and CKD may be related. DCE parameters and MRI T2∗ could serve as imaging biomarkers of cartilage degeneration in CKD progression.

Thiophene and diaminobenzo- (1,2,5-thiadiazol)- based DAD-type near-infrared fluorescent probe for nitric oxide: A theoretical research.

A near-infrared fluorescent probe (LS-NO) for the real-time detection of nitric oxide (NO) in inflammatory bowel disease (IBD) was developed recently. The probe used oligoglycol morpholine-functionalized thiophene as strong electron donors and diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor and NO trapping group. It could detect exogenous and endogenous NO in the lysosomes of living cells with high sensitivity and specificity. To further understand the fluorescent mechanism and character of the probes LS-NO and LS-TZ (after the reaction of the probe LS-NO with NO), the electron transfer in the excitation and emitting process within the model molecules DAD-NO and DAD-TZ was analyzed in detail under the density functional theory. The calculation results indicated the transformation from diaminobenzene (1,2,5-thiadiazole) as a weak electron acceptor to triazolo-benzo-(1,2,5-thiadiazole) as a strong electron acceptor made LS-NO an effective "off-on" near-infrared NO fluorescent probe.

NADPH oxidase is required for the sensory plasticity of the carotid body by chronic intermittent hypoxia.

Respiratory motoneuron response to hypoxia is reflex in nature and carotid body sensory receptor constitutes the afferent limb of this reflex. Recent studies showed that repetitive exposures to hypoxia evokes long term facilitation of sensory nerve discharge (sLTF) of the carotid body in rodents exposed to chronic intermittent hypoxia (CIH). Although studies with anti-oxidants suggested the involvement of reactive oxygen species (ROS)-mediated signaling in eliciting sLTF, the source of and the mechanisms associated with ROS generation have not yet been investigated. We tested the hypothesis that ROS generated by NADPH oxidase (NOX) mediate CIH-evoked sLTF. Experiments were performed on ex vivo carotid bodies from rats and mice exposed either to 10 d of CIH or normoxia. Acute repetitive hypoxia evoked a approximately 12-fold increase in NOX activity in CIH but not in control carotid bodies, and this effect was associated with upregulation of NOX2 mRNA and protein, which was primarily localized to glomus cells of the carotid body. sLTF was prevented by NOX inhibitors and was absent in mice deficient in NOX2. NOX activation by CIH required 5-HT release and activation of 5-HT(2) receptors coupled to PKC signaling. Studies with ROS scavengers revealed that H(2)O(2) generated from O(2).(-) contributes to sLTF. Priming with H(2)O(2) elicited sLTF of carotid bodies from normoxic control rats and mice, similar to that seen in CIH-treated animals. These observations reveal a novel role for NOX-induced ROS signaling in mediating sensory plasticity of the carotid body.

Long-term regulation of carotid body function: acclimatization and adaptation--invited article.

Physiological responses to hypoxia either continuous (CH) or intermittent (IH) depend on the O(2)-sensing ability of the peripheral arterial chemoreceptors, especially the carotid bodies, and the ensuing reflexes play important roles in maintaining homeostasis. The purpose of this article is to summarize the effects of CH and IH on carotid body function and the underlying mechanisms. CH increases baseline carotid body activity and sensitizes the response to acute hypoxia. These effects are associated with hyperplasia of glomus cells and neovascularization. Enhanced hypoxic sensitivity is due to alterations in ion current densities as well as changes in neurotransmitter dynamics and recruitment of additional neuromodulators (endothelin-1, ET-1) in glomus cells. Morphological alterations are in part due to up-regulation of growth factors (e.g. VEGF). Hypoxia-inducible factor-1 (HIF-1), a transcriptional activator might underlie the remodeling of carotid body structure and function by CH. Chronic IH, on the other hand, is associated with recurrent apneas in adults and premature infants. Two major effects of chronic IH on the adult carotid body are sensitization of the hypoxic sensory response and long-lasting increase in baseline activity i.e., sensory long-term facilitation (LTF) which involve reactive oxygen species (ROS) and HIF-1. In neonates, chronic IH leads to sensitization of the hypoxic response but does not induce sensory LTF. Chronic IH-induced sensitization of the carotid body response to hypoxia increases the likelihood of unstable breathing perpetuating in more number of apneas, whereas sensory LTF may contribute to increased sympathetic tone and systemic hypertension associated with recurrent apneas.

Abnormal methylation of spermatozoa induced by benzo(a)pyrene in rats.

Epigenetic mutations caused by pollutants are possibly linked to many diseases. Benzo(a)pyrene (BaP) is one of the most representative air pollutants and has aroused wide concern because of its strong carcinogenicity. The reproductive toxicity induced by BaP has been identified, but little is known about the characteristics of the methylation changes induced by BaP. In this study, a methylated DNA immunoprecipitation sequencing method was used to detect the methylation of sperm DNA of rats exposed to BaP. Compared with the respective genes in normal rats, there were 3227 hypomethylated genes and 828 hypermethylated genes after BaP exposure. Gene ontology enrichment analysis reported that differentially methylated genes (DMGs) were enriched in the localization, single-multicellular organism process and plasma membrane. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the DMGs were significantly enriched in the Ras signalling pathway, Rap1 signalling pathway, pancreatic secretion and neuroactive ligand-receptor interaction. DisGeNET disease spectrum analysis showed that DMGs were associated with infertility and certain genetic diseases. Further research needs to be done to explore whether these abnormal methylation are transgenerational.

Acute lung injury augments hypoxic ventilatory response in the absence of systemic hypoxemia.

The objective of the present study was to examine the impact of early stages of lung injury on ventilatory control by hypoxia and hypercapnia. Lung injury was induced with intratracheal instillation of bleomycin (BM; 1 unit) in adult, male Sprague-Dawley rats. Control animals underwent sham surgery with saline instillation. Five days after the injections, lung injury was present in BM-treated animals as evidenced by increased neutrophils and protein levels in bronchoalveolar lavage fluid, as well as by changes in lung histology and computed tomography images. There was no evidence of pulmonary fibrosis, as indicated by lung collagen content. Basal core body temperature, arterial Po(2), and arterial Pco(2) were comparable between both groups of animals. Ventilatory responses to hypoxia (12% O(2)) and hypercapnia (7% CO(2)) were measured by whole body plethysmography in unanesthetized animals. Baseline respiratory rate and the hypoxic ventilatory response were significantly higher in BM-injected compared with control animals (P = 0.003), whereas hypercapnic ventilatory response was not statistically different. In anesthetized, spontaneously breathing animals, response to brief hyperoxia (Dejours' test, an index of peripheral chemoreceptor sensitivity) and neural hypoxic ventilatory response were augmented in BM-exposed relative to control animals, as measured by diaphragmatic electromyelograms. The enhanced hypoxic sensitivity persisted following bilateral vagotomy, but was abolished by bilateral carotid sinus nerve transection. These data demonstrate that afferent sensory input from the carotid body contributes to a selective enhancement of hypoxic ventilatory drive in early lung injury in the absence of pulmonary fibrosis and arterial hypoxemia.

Modulation of the hypoxic sensory response of the carotid body by 5-hydroxytryptamine: role of the 5-HT2 receptor.

Previous studies have shown that glomus cells of the carotid body express 5-hydroxytryptamine (5-HT). The aim of this study was to elucidate the role of 5-HT on the hypoxic sensory response (HSR) of the carotid body. Sensory activity was recorded from multi-fiber (n=16) and single-fiber (n=8) preparations of ex vivo carotid bodies harvested from anesthetized, adult rats. 5-HT (3 microM) had no significant effect on the magnitude or on the onset of the HSR. However, 5-HT consistently prolonged the time necessary for the sensory activity to return to baseline following the termination of the hypoxic challenge. Ketanserin (40 microM), a 5-HT2 receptor antagonist completely prevented 5-HT-induced prolongation of the HSR, whereas had no effect on the control HSR (onset, magnitude, and time for decay without 5-HT). Carotid bodies expressed 5-HT, but hypoxia did not facilitate 5-HT release. These observations suggest that 5-HT is not critical for the HSR of the rat carotid body, but it modulates the dynamics of the HSR via its action on 5-HT2 receptors.

GABA(A) receptors in the rostral ventrolateral medulla mediate the depressor response induced by stimulation of the greater splanchnic nerve afferent fibres in rats.

Experiments have been carried out to investigate the chemical substrate in the rostral ventrolateral medulla (RVLM) underlying the depressor responses induced by activation of the greater splanchnic nerve (GSPL) afferent fibres of the rat. In anaesthetised rats with urethane and alpha-chloralose, microinjection of bicuculline, a GABA(A) receptor antagonist, into the RVLM, attenuated largely the depressor responses elicited by electrical stimulation of the GSPL afferent fibres, while strychnine or saline had no effect. In 18 RVLM neurons (including seven identified cardiovascular neurons), iontophoresis of bicuculline also significantly blocked the inhibition evoked by stimulation of the GSPL afferent inputs. We suggest that the depressor responses induced by stimulation of the GSPL afferent fibres involve a GABA(A)-receptor-mediated mechanism in the RVLM in rats.

Blood flow velocity estimation from x-ray densitometric data: an efficient numerical scheme for the inverse advection problem.

In previously published studies, blood flow velocity from x-ray biplane angiography was measured by solving an inverse advection problem, relating velocity to bolus densities summed across sections. Both spatial and temporal velocity variations were recovered through a computationally expensive parameter estimation algorithm. Here we prove the existence and uniqueness of the solution on three sub-domains of the plane defined by the axial position along the vessel and the time of the angiographic sequence. A fast direct scheme was designed in conjunction with a regularization step stemming from the volume flow conservation law applied on consecutive segments. Its accuracy and immunity towards noise were tested on both simulated and real densitometric data. The relative error between the estimated and expected velocities was less than 5% for more than 90% of the points of the spatiotemporal plane with simulated densities normalized to 1.0 and a Gaussian additive noise of standard deviation 0.01. For densities reconstructed from a biplane angiographic sequence, increase in velocity is used as a functional index for the stenosis ratio and to characterize the sharing of flow at bifurcation.

Convergence of midbrain, visceral and somatic inputs onto neurons in the nucleus paragigantocellularis lateralis in rats.

Extracellular recordings were made in nucleus paragigantocellularis lateralis (PGL) of the rat in response to stimulation of the dorsal periaqueductoral gray matter (dPAG), ventrolateral periaqueductuctoral gray matter (vPAG), deep peroneal nerve (DPN), median nerve (MN) and great splanchnic nerve (GSPL). Stimulation of dPAG or MN evoked mainly excitatory responses while the responses to stimulation of vPAG were inhibitory. However, stimulation of GSPL or DPN produced both inhibitory and excitatory responses. These neurons were not only responsive to one stimulation site, but were likely responsive to any other stimulation sites. Eighty-nine percent of cells tested (73/82) received convergent inputs from two or more sites. Sixty percent (21/35) of the neurons were identified as cardiovascular units based on their barosensitivity and slow conduction velocities of the descending axons projecting into the spinal cord. This result provided new evidence for the integrative function of neurons in PGL under some circumstances.