Allele-dependent interaction of LRRK2 and NOD2 in leprosy.

Leprosy, caused by Mycobacterium leprae, rarely affects children younger than 5 years. Here, we studied a multiplex leprosy family that included monozygotic twins aged 22 months suffering from paucibacillary leprosy. Whole genome sequencing identified three amino acid mutations previously associated with Crohn's disease and Parkinson's disease as candidate variants for early onset leprosy: LRRK2 N551K, R1398H and NOD2 R702W. In genome-edited macrophages, we demonstrated that cells expressing the LRRK2 mutations displayed reduced apoptosis activity following mycobacterial challenge independently of NOD2. However, employing co-immunoprecipitation and confocal microscopy we showed that LRRK2 and NOD2 proteins interacted in RAW cells and monocyte-derived macrophages, and that this interaction was substantially reduced for the NOD2 R702W mutation. Moreover, we observed a joint effect of LRRK2 and NOD2 variants on Bacillus Calmette-Guérin (BCG)-induced respiratory burst, NF-κB activation and cytokine/chemokine secretion with a strong impact for the genotypes found in the twins consistent with a role of the identified mutations in the development of early onset leprosy.

Predicting Severity in Hypertriglyceridemia-Induced Acute Pancreatitis: The Role of Neutrophils, Calcium, and Apolipoproteins.

BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more severe progression, often leading to higher ICU admission rates. This condition poses a significant challenge due to its rapid progression and the potential for severe complications, including multiple organ failure. HTG-AP is distinct from other forms of pancreatitis, such as those caused by cholelithiasis or alcohol, in terms of clinical presentation and outcomes. It's essential to identify early markers that can predict the severity of HTG-AP to improve patient management and outcomes. MATERIAL AND METHODS This study divided 127 HTG-AP patients into mild acute pancreatitis (MAP, n=71) and moderate-to-severe acute pancreatitis (MSAP/SAP, n=56) groups. Blood biological indicators within the first 24 hours of admission were analyzed. Risk factors for HTG-AP progression were determined using binary logistic regression and ROC curves. RESULTS Elevated levels of HCT, NLR, TBI, DBI, AST, Cre, and AMS were noted in the MSAP/SAP group, with lower levels of LYM, Na⁺, Ca²âº, ApoA, and ApoB compared to the MAP group (p<0.05). NEUT%, Ca²âº, ApoA, and ApoB were significantly linked with HTG-AP severity. Their combined ROC analysis yielded an area of 0.81, with a sensitivity of 61.8% and specificity of 90%. CONCLUSIONS NEUT%, Ca²âº, ApoA, and ApoB are significant risk factors for progressing to MSAP/SAP in HTG-AP. Their combined assessment provides a reliable predictive measure for early intervention in patients at risk of severe progression.

Selective EZH2 inhibitor zld1039 alleviates inflammation in cisplatin-induced acute kidney injury partially by enhancing RKIP and suppressing NF-κB p65 pathway.

Enhancer of zeste homolog 2 (EZH2), a component of polycomb repressive complex 2 (PRC2), is a histone lysine methyltransferase mediating trimethylation of histone H3 at lysine 27 (H3K27me3), which is a repressive marker at the transcriptional level. EZH2 sustains normal renal function and its overexpression has bad properties. Inhibition of EZH2 overexpression exerts protective effect against acute kidney injury (AKI). A small-molecule compound zld1039 has been developed as an efficient and selective EZH2 inhibitor. In this study, we evaluated the efficacy of zld1039 in the treatment of cisplatin-induced AKI in mice. Before injection of cisplatin (20 mg/kg, i.p.), mice were administered zld1039 (100, 200 mg/kg, i.g.) once, then in the following 3 days. We found that cisplatin-treated mice displayed serious AKI symptoms, evidenced by kidney dysfunction and kidney histological injury, accompanied by EZH2 upregulation in the nucleus of renal tubular epithelial cells. Administration of zld1039 dose-dependently alleviated renal dysfunction as well as the histological injury, inflammation and cell apoptosis in cisplatin-treated mice. We revealed that zld1039 administration exerted an anti-inflammatory effect in kidney of cisplatin-treated mice via H3K27me3 inhibition, raf kinase inhibitor protein (RKIP) upregulation and NF-κB p65 repression. In the cisplatin-treated mouse renal tubular epithelial (TCMK-1) cells, silencing of RKIP with siRNA did not abolish the anti-inflammatory effect of EZH2 inhibition, suggesting that RKIP was partially involved in the anti-inflammatory effect of zld1039. Collectively, EZH2 inhibition alleviates inflammation in cisplatin-induced mouse AKI via upregulating RKIP and blocking NF-κB p65 signaling in cisplatin-induced AKI. The potent and selective EZH2 inhibitor zld1039 has the potential as a promising agent for the treatment of AKI.

Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson's disease.

Type-1 reactions (T1R) are pathological inflammatory episodes and main contributors to nerve damage in leprosy. Here, we evaluate the genewise enrichment of rare protein-altering variants in 7 genes where common variants were previously associated with T1R. We selected 474 Vietnamese leprosy patients of which 237 were T1R-affected and 237 were T1R-free matched controls. Genewise enrichment of nonsynonymous variants was tested with both kernel-based (sequence kernel association test [SKAT]) and burden methods. Of the 7 genes tested 2 showed statistical evidence of association with T1R. For the LRRK2 gene an enrichment of nonsynonymous variants was observed in T1R-free controls (PSKAT-O = 1.6 × 10-4). This genewise association was driven almost entirely by the gain-of-function variant R1628P (P = 0.004; odds ratio = 0.29). The second genewise association was found for the Parkin coding gene PRKN (formerly PARK2) where 7 rare variants were enriched in T1R-affected cases (PSKAT-O = 7.4 × 10-5). Mutations in both PRKN and LRRK2 are known causes of Parkinson's disease (PD). Hence, we evaluated to what extent such rare amino acid changes observed in T1R are shared with PD. We observed that amino acids in Parkin targeted by nonsynonymous T1R-risk mutations were also enriched for mutations implicated in PD (P = 1.5 × 10-4). Hence, neuroinflammation in PD and peripheral nerve damage due to inflammation in T1R share overlapping genetic control of pathogenicity.

Efficacy of Optimized Treatment Protocol Using LAU-7b Formulation against Ovalbumin (OVA) and House Dust Mite (HDM) -Induced Allergic Asthma in Atopic Hyperresponsive A/J Mice.

PURPOSE: To assess the efficacy of the novel clinical formulation of fenretinide (LAU-7b) for the treatment of allergic asthma. To study the association between LAU-7b treatment in allergic asthma and the modulation of very long chain ceramides (VLCC). METHODS: We used two allergens (OVA and HDM) to induce asthma in mouse models and we established a treatment protocol with LAU-7b. The severity of allergic asthma reaction was quantified by measuring the airway resistance, quantifying lung inflammatory cell infiltration (Haematoxylin and eosin stain) and mucus production (Periodic acid Schiff satin). IgE levels were measured by ELISA. Immunophenotyping of T cells was done using Fluorescence-activated cell sorting (FACS) analysis. The analysis of the specific species of lipids and markers of oxidation was performed using mass spectrometry. RESULTS: Our data demonstrate that 10 mg/kg of LAU-7b was able to protect OVA- and HDM-challenged mice against increase in airway hyperresponsiveness, influx of inflammatory cells into the airways, and mucus production without affecting IgE levels. Treatment with LAU-7b significantly increased percentage of regulatory T cells and CD4+ IL-10-producing T cells and significantly decreased percentage of CD4+ IL-4-producing T cells. Our data also demonstrate a strong association between the improvement in the lung physiology and histology parameters and the drug-induced normalization of the aberrant distribution of ceramides in allergic mice. CONCLUSION: 9 days of 10 mg/kg of LAU-7b daily treatment protects the mice against allergen-induced asthma and restores VLCC levels in the lungs and plasma.

Elevated levels of cerebrospinal fluid S100B are associated with brain injury and unfavorable outcomes in children with central nervous system infections.

PURPOSE: This work aimed to assess whether elevated levels of cerebrospinal fluid (CSF) S100B are associated with brain injury and unfavorable outcomes at discharge in children with central nervous system (CNS) infections. METHODS: CSF S100B and associated clinical parameters were retrospectively analyzed in 83 children with CNS infections and 88 children without neurological pathology served as controls. Children with CNS infections were divided into an infectious encephalitis group and an infectious meningitis group based on whether cerebral parenchyma was involved, and CSF S100B levels in different age subgroups between the two groups were compared. The predictive value of CSF S100B in children with infectious encephalitis was evaluated by multivariate logistic regression analysis, and the discriminative power was investigated by receiver operating characteristic (ROC) analysis. RESULTS: CSF S100B levels in the infectious encephalitis group were significantly higher than the infectious meningitis and the control group at each age range. CSF S100B ≥ 0.96 µg/L had 62.9% sensitivity and 76.2% specificity for diagnosing cerebral parenchyma injury in children with CNS infections. Increased CSF S100B levels were proven to be an independent predictor of unfavorable outcomes in children with infectious encephalitis and the optimal cut-off value (1.77 µg/L of CSF S100B) for predicting unfavorable outcomes in children with infectious encephalitis showed 61.1% sensitivity and 96.2% specificity. CONCLUSIONS: This study has demonstrated that elevated levels of CSF S100B are associated with brain injury and could be used as an independent predictor of clinically unfavorable outcomes at discharge in children with CNS infections.

Enterovirus-related diarrhoea in Guangdong, China: clinical features and implications in hand, foot and mouth disease and herpangina.

BACKGROUND: A series of complications caused by enteroviruses, including meningitis, encephalitis, acute flaccid paralysis, acute cardiopulmonary failure, respiratory infection, and myocardial injury have been reported in hand, foot and mouth disease/herpangina (HFMD/HA). However, the complication of diarrhoea caused by enteroviruses has been neglected, and a summary of its clinical features and impact on HFMD/HA is unavailable. METHODS: We included inpatients with HFMD/HA admitted to the Paediatric Department of Zhujiang Hospital during 2009-2012. We summarised and compared clinical data for cases with and without diarrhoea, and determined enterovirus serotypes by reverse transcriptase polymerase chain reaction and genotyping based on a partial-length fragment of viral protein 1 or the 5'-untranslated region. RESULTS: There were 804 inpatients with HFMD/HA and 28 (3.5%) presented with diarrhoea. Gastrointestinal symptoms were mild in most cases of diarrhoea (82.1%), with high prevalence of no dehydration (82.1%), short duration of diarrhoea (78.6%) and watery stools (75.0%). The prevalence of multi-organ dysfunction syndrome (10.7 vs 0.40%) (p = 0.001), hepatic injury (14.3 vs 3.4%) (p = 0.019), myocardial injury (21.4 vs 6.1%) (p = 0.002) and convulsion (21.4 vs 7.2%) (p = 0.016) was significantly higher in the diarrhoea than no diarrhoea group. There was no significant difference between the two groups regarding prevalence of death, altered consciousness, paralysis, central nervous system involvement, or acute respiratory infection. CONCLUSIONS: Most patients with diarrhoea caused by enteroviruses circulating in Guangdong Province in 2009-2012 had mild or moderate gastrointestinal symptoms. Although enterovirus-related diarrhoea caused additional multi-organ dysfunction syndrome, hepatic injury and myocardial injury in children with HFMD/HA, timely intervention efficiently reduced disease severity and improved outcome.

Changes in enterovirus serotype constituent ratios altered the clinical features of infected children in Guangdong Province, China, from 2010 to 2013.

BACKGROUND: Enterovirus (EV)-related hand, foot, and mouth disease/herpangina (HFMD/HA) has been prevalent in Guangdong Province, China, since 2010. METHODS: Clinical data for EV-related HFMD/HA inpatients admitted to the Department of Paediatrics of Zhujiang Hospital from 2010 to 2013 were retrospectively reviewed. The corresponding EV serotypes were also determined by reverse transcription-polymerase chain reaction or BLAST analysis of the sequenced partial lengths of the viral protein1/5'-untranslated region. RESULTS: A total of 867 eligible inpatients admitted during 2010-2013 were included in the study. Of these, the serotype of the responsible EV was successfully identified in 824 cases. The incidence of enterovirus 71 (EV71) infection amongst pediatric HFMD/HA inpatients decreased dramatically from 55.5 % in 2010 to 8.1 % in 2013, with a similar decrease recorded for coxsackievirus A16 (CVA16). However, the incidence of non-EV71/CVA16 infection increased from 30.0 % in 2010 to 83.8 % in 2013. We noted that the types of infection caused by different EV serotypes varied: EV71 was responsible for 100 % of the paralysis cases (26/26), 84.6 % of the deaths (11/13), and 84.1 % of cases with severe central nervous system involvement (SCNSI) (74/88); echovirus contributed to 16.4 % of the deaths (2/13) and 4.4 % of the SCNSI cases; and coxsackievirus accounted for only 2.2 % of the SCNSI cases (2/90). The clinical features of HFMD/HA cases varied greatly during the time period examined, with drastic changes in the hospitalization rates (45.1, 63.7, 36.4, and 19.1 % for 2010, 2011, 2012, and 21013, respectively), mortality rates (2.3, 0.9, 2.5, and 0.0 %, respectively), paralysis (5.1, 1.2, 5.4, and 0.0 %, respectively), SCNSI (16.8, 7.1, 12.7, and 2.2 %, respectively), and acute respiratory infection (21.1, 22.0, 45.9, and 59.0 %, respectively). CONCLUSIONS: The incidences of infection caused by different EV serotypes, along with the clinical features of HFMD/HA cases, changed drastically in Guangdong Province, China, from 2010 to 2013, with the biggest changes observed in 2013. The changed constituent ratios of the different EV serotypes might therefore be responsible for the differences in the observed clinical features of HFMD/HA during this period.

[A Detection Technique for Gas Concentration Based on the Spectral Line Shape Function].

The methods that can rapidly and precisely measure concentrations of various gases have extensive applications in the fields such as air quality analysis, environmental pollution detection, and so on. The gas detection method based on the tunable laser absorption spectroscopy is considered a promising technique. For the infrared spectrum detection techniques, the line shape function of an absorption spectrum of a gas is an important parameter in qualitative and quantitative analysis of a gas. Specifically, how to obtain the line shape function of an absorption spectrum of a gas quickly and accurately is a key problem in the gas detection fields. In this paper we analyzed several existing line shape functions and proposed a method to calculate precisely the line shape function of a gas, and investigated the relation between the gas concentration and the peak value of a line shape function. Then we experimentally measured the absorption spectra of an acetylene gas in the wavelength range of 1,515-1,545 nm with a tunable laser source and a built-in spectrometer. With Lambert-Beer law we calculated the peak values of the line shape function of the gas at the given frequencies, and obtained a fitting curve for the line shape function in the whole waveband by using a computer program. Comparing the measured results with the calculated results of the Voigt function, we found that there was a deviation-between the experimental results and the calculated results. And we found that the measured concentration of the acetylene gas by using the fitting curve of the line shape function was more accurate and compatible with the actual situation. Hence, the empirical formula for the line shape function obtained from the experimental results would be more suitable for the concentration measurement of a gas. As the fitting curve for the line shape function of the acetylene gas has been deduced from the experiment, the corresponding peak values of the spectral lines can be immediately calculated out from the curve and used for the measurements of different concentrations of acetylene gases. Therefore, the calculation for the line shape function values is greatly simplified. The obtained data of the line shape function of the acetylene gas can be used for remote sensing of the gas, and the proposed method can also be applied for the measurements of line shape functions of other gases.

[Gas Concentration Measurement Based on the Integral Value of Absorptance Spectrum].

The absorptance spectrum of a gas is the basis for the qualitative and quantitative analysis of the gas by the law of the Lambert-Beer. The integral value of the absorptance spectrum is an important parameter to describe the characteristics of the gas absorption. Based on the measured absorptance spectrum of a gas, we collected the required data from the database of HIT-RAN, and chose one of the spectral lines and calculated the integral value of the absorptance spectrum in the frequency domain, and then substituted the integral value into Lambert-Beer's law to obtain the concentration of the detected gas. By calculating the integral value of the absorptance spectrum we can avoid the more complicated calculation of the spectral line function and a series of standard gases for calibration, so the gas concentration measurement will be simpler and faster. We studied the changing trends of the integral values of the absorptance spectrums versus temperature. Since temperature variation would cause the corresponding variation in pressure, we studied the changing trends of the integral values of the absorptance spectrums versus both the pressure not changed with temperature and changed with the temperature variation. Based on the two cases, we found that the integral values of the absorptance spectrums both would firstly increase, then decrease, and finally stabilize with temperature increasing, but the ranges of specific changing trend were different in the two cases. In the experiments, we found that the relative errors of the integrated values of the absorptance spectrum were much higher than 1% and still increased with temperature when we only considered the change of temperature and completely ignored the pressure affected by the temperature variation, and the relative errors of the integrated values of the absorptance spectrum were almost constant at about only 1% when we considered that the pressure were affected by the temperature variation. As the integral value of the absorptance spectrum varied with temperature and the calculating error for the integral value fluctuates with ranges of temperature, in the gas measurement when we usd integral values of the absoptance spectrum, we should select a suitable temperature variation and obtain a more accurate measurement result.

[A preliminary study of long-term mitochondrial dysfunction in rat brain caused by lipopolysaccharide-induced sepsis].

OBJECTIVE: To preliminarily investigate the long-term structural and functional injuries of mitochondria in rat brain caused by sepsis. METHODS: Wistar rats were randomly assigned into sepsis and control groups. A rat model of sepsis was prepared by an intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS) of gram-negative bacteria, and the survival assay was performed. Eight rats in the sepsis group were sacrificed at 12, 24, 48, or 72 hours after LPS injection, while rats in the control group were sacrificed after an intraperitoneal injection of an equal volume of normal saline. Mitochondria were extracted from rat brain tissue. Mitochondrial membrane potential (MMP) and mitochondrial swelling level were determined by flow cytometry, and the activities of electron transport chain complexes (I-V) were measured using enzyme assay kits. Hematoxylin-eosin (HE) staining and electron microscopy were used to observe morphological changes in brain tissue and mitochondria. RESULTS: The sepsis group had a significantly lower survival rate than the control group (P<0.01). The MMP and activities of electron transport chain complexes (I-V) in the sepsis group, which were significantly lower than those in the control group (P<0.05), were reduced to the lowest levels at 48 hours and partially recovered at 72 hours. The mitochondrial swelling level in the sepsis group, which was significantly higher than that in the control group (P<0.05), increased to the peak level at 48 hours and partially recovered at 72 hours. Hematoxylin and Eosin staining revealed substantial damages in the structure of brain tissue, and electron microscopy showed mitochondrial swelling, and vacuolization in a few mitochondria. CONCLUSIONS: In the rat model of LPS-induced sepsis, both structural and functional injuries are found in cerebral mitochondria, and achieve the peak levels probably at around 48 hours.

Mast cell degranulation promotes ischemia-reperfusion injury in rat liver.

BACKGROUND: Mast cells (MCs) play a role in ischemia-reperfusion (I/R) injury in many organs. However, a recent study found that MCs are not involved in I/R injury in isolated rat livers that were perfused only for 1 h. The purpose of this study is to reevaluate the role of MCs in hepatic I/R injury in rat. MATERIALS AND METHODS: A warm hepatic I/R injury model of 1 h ischemia followed by 24 h of reperfusion was used. MC modulation was induced via cromolyn injection or a method called MC depletion using compound 48/80. The effects of MC modulation were evaluated by toluidine blue staining and assessment of mast cell tryptase in sera. The role of MCs in I/R injury was evaluated by hematoxylin and eosin staining graded by Suzuki criteria, alanine aminotransferase and aspartate aminotransferase levels in sera, and malondialdehyde levels in liver homogenates. RESULTS: First, MC degranulation peaked after 2 h of reperfusion and liver damage peaked after approximately 6 h of reperfusion. Second, a method called MC depletion previously used in the skin with repeated injections of compound 48/80 worked similarly in the hepatic setting. Third, stabilization of MCs with cromolyn or depletion of MCs with compound 48/80 each decreased hepatic I/R injury. The most noticeable effects of cromolyn and compound 48/80 treatment were observed after approximately 6 h of reperfusion. CONCLUSIONS: MC degranulation promotes hepatic I/R injury in rats.

Cellulose nanofiber/MXene (Ti3C2Tx)/liquid metal film as a highly performance and flexible electrode material for supercapacitors.

In recent times, there has been significant interest in the utilization of cellulose nanofiber (CNF) films as the foundation for supercapacitors due to their three-dimensional structure, flexibility and eco-friendliness. An ultrasonic and vacuum filtration method was used to prepare a hybrid film consisting of MXene (Ti3C2Tx), CNF and liquid metal (LM). The combination of CNF and LM with MXene produces a porous structure with higher electrical conductivity, which facilitates the transportation of ions and electrons within the composition and confers the material with heightened electrochemical properties. The CNF/MXene/LM electrode has a significant area capacitance of 871.3 mF cm-2 at a current density of 5 mA cm-2. The hybrid film demonstrates excellent stability, maintaining a high conductivity of 546.4 S∙cm-1 and retaining 96.9 % capacitance after 2000 cycles at a current density of 10 mA cm-2. By utilizing the thin film as an electrode, a high-performance quasi-solid supercapacitor was fabricated, with a remarkably thin thickness of only 0.319 mm. Supercapacitors show exceptional electrical properties, including a surface-specific capacitance of 188.2 mF cm-2 at a current density of 5 mA cm-2. This study indicates that flexible electrodes made from cellulose nanofiber have extensive potential in the realm of supercapacitors.

Establishment and Verification of an Artificial Intelligence Prediction Model for Children With Sepsis.

BACKGROUND: Early identification of high-risk groups of children with sepsis is beneficial to reduce sepsis mortality. This article used artificial intelligence (AI) technology to predict the risk of death effectively and quickly in children with sepsis in the pediatric intensive care unit (PICU). STUDY DESIGN: This retrospective observational study was conducted in the PICUs of the First Affiliated Hospital of Sun Yat-sen University from December 2016 to June 2019 and Shenzhen Children's Hospital from January 2019 to July 2020. The children were divided into a death group and a survival group. Different machine language (ML) models were used to predict the risk of death in children with sepsis. RESULTS: A total of 671 children with sepsis were enrolled. The accuracy (ACC) of the artificial neural network model was better than that of support vector machine, logical regression analysis, Bayesian, K nearest neighbor method and decision tree models, with a training set ACC of 0.99 and a test set ACC of 0.96. CONCLUSIONS: The AI model can be used to predict the risk of death due to sepsis in children in the PICU, and the artificial neural network model is better than other AI models in predicting mortality risk.

[Accurate calculation of spectral line profiles by considering influence of varying pressure and temperature in a gas].

Accurate calculation of spectral line profiles of a gas is very important for gas sensing. As we know, a variation in pressure (temperature) of a gas will result in the corresponding variation in temperature (pressure) of the gas. In the present paper we calculated spectral line profiles of a gas by considering the changes in both temperature and pressure. The authors found that in our case the Lorentzian profile has broader applicable ranges of pressure and temperature, and the Gaussian profile is only applicable in some extreme conditions. Furthermore, the authors found that the influence of variations in pressure and temperature has to be considered in calculating the peak values of the spectral line profiles such as Gaussian, Lorentzian, and Voigt; otherwise the resultant relative errors of the calculated peak values can exceed 0.1. The similar observations were also found for other gases such as CH4, CO2, CO, and NO, although the parameters such as wavelength, coefficient of pressure-broadening, relative molecular mass, and temperature were different.

Surgical treatment of severe benign tracheal stenosis.

OBJECTIVE: To present clinical experiences regarding surgical treatment of patients with severe cicatricial tracheal stenosis. PATIENTS AND METHODS: From January 2008 to March 2020, 14 patients underwent tracheal resection and reconstruction under general anesthesia. Nine cases had cervical tracheal stenosis and five cases had thoracic tracheal stenosis. The mean diameter and length of strictured trachea was 0 - 8 mm with a mean of 4.5 ± 2.4 mm and 1 - 3 cm with a mean of 1.67 ± 0.63 cm, respectively. General anesthesia and mechanical ventilation were performed in ten cases and four patients underwent femoral arteriovenous bypass surgery due to severe stenosis. End-to-end anastomosis of trachea was performed in 13 cases and the anastomosis between trachea and cricothyroid membrane was performed in one case. Absorbable and unabsorbable sutures were used for the anterior and posterior anastomoses, respectively. Postoperative neck anteflexion was maintained by a suture between the chin and superior chest wall. The relevant data of the 14 patients were retrospectively reviewed, and the operation time, blood loss, postoperative hospital stay, postoperative complications and follow-up were retrieved. RESULTS: There was no intraoperative death. The length of resected trachea ranged from 1.5 to 4.5 cm with a mean of 1.67 ± 0.63 cm. Operation time ranged from 50 - 450 min with a mean of 142.8 ± 96.6 min and intraoperative hemorrhage ranged from 10 - 300 ml with a mean of 87.8 ± 83.6 ml. Follow-up period ranged from 5 to 43 months with a mean of 17.9 ± 10.6 months. None of the patients had recurrent laryngeal nerve paralysis during postoperative follow-up. Ten cases were discharged uneventfully. Anastomosis stenosis occurred in three cases who received interventional therapies. Bronchopleurocutaneous fistula occurred in one patient after 6 days postoperatively and further treatment was declined. CONCLUSION: The strategies of anesthesia, mechanical ventilation, identification of stenosis lesion, the "hybrid" sutures and postoperative anteflexion are critical to be optimized for successful postoperative recovery.

Multi-center experience in an optimized right upper lobectomy surgical procedure in China.

BACKGROUND: This multi-center study was aimed at retrospectively evaluating the feasibility, safety, clinical outcomes, and surgical learning curve of an optimized procedure for right upper lobectomy (RUL), which is challenging because of the anatomical structures and features of this lobe. METHODS: This study included 45 RUL cases of robot-assisted thoracoscopy (RATS) in a pilot cohort and 187 RUL cases of video-assisted thoracoscopy (VATS) in three cohorts. A total of 121 and 111 patients underwent traditional and optimized RUL, respectively. The optimized surgical procedure was performed to consecutively transect the superior arterial trunk and bronchus, and finally disconnect the pulmonary vein and posterior ascending artery with interlobar fissures. Clinical and radiological data were reviewed retrospectively. RESULTS: Optimized RUL can be performed successfully by RATS or VATS. The optimized procedure yielded better clinical outcomes than the traditional procedure, including shorter operation times, less blood loss, fewer complications, shorter hospital times, lower costs, and a lower likelihood of postoperative intermedius bronchial kinking. Additionally, for calcified interlobar lymph nodes, the optimized VATS group was less likely to be converted to thoracotomy than the traditional group. The skills required to perform optimized VATS RUL can be gained by surgeons after 12 to 15 cases. The two RUL procedures in the pilot cohort showed similar disease-free survival. CONCLUSIONS: The optimized RUL was safe, economical, and feasible, with a short learning curve and satisfactory disease-free survival.

Preconditioning donor liver with Nodosin perfusion lessens rat ischemia reperfusion injury via heme oxygenase-1 upregulation.

BACKGROUND AND AIM: Ischemia reperfusion injury (IRI) remains a major cause of graft injury, dysfunction and even failure post-transplantation. Heme oxygenase 1 (HO-1) has been found to be an attractive target for anti-inflammatory therapies and a potential candidate responsible for cell injury. The objective of this study was to investigate whether preconditioning the donor liver with Nodosin perfusion upregulates HO-1 and then lessens IRI in rat models. METHODS: Wistar rats were divided into four groups: experimental group, control group, positive control group and negative control group in which the donor liver was preconditioned with Nodosin, lactated ringer's solution, cobalt protoporphyrin and zinc protoporphyrin perfusion, respectively. We measured HO-1 expression and enzyme activity in rat livers of each group ex vivo at 0, 1 and 2 h after perfusion. At 1 h after perfusion, donor livers of Wistar rats were transplanted into Sprague-Dawley rats orthotopically. Serum transaminase levels, degree of cell apoptosis and Suzuki's score were used to assess ischemia/reperfusion injury in recipients at 24 h after transplantation. RESULTS: Ex vivo, donor liver preconditioning with Nodosin perfusion induced HO-1 expression and enzyme activity significantly, compared with the control group (P < 0.05). In vivo, serum transaminase levels, cell apoptosis degree and Suzuki's score of representative recipients in the Nodosin group were lower than that in the control group (P < 0.05). Preconditioning with Nodosin perfusion induced HO-1 protein mainly in Kupffer cells. CONCLUSIONS: This study suggests that preconditioning with Nodosin perfusion provides a potential protective effect through inducing HO-1 expression to attenuate ischemia/reperfusion injury in liver transplantation.

Tension-compression viscoelastic behaviors of the periodontal ligament.

BACKGROUND/PURPOSE: Although exhaustively studied, the mechanism responsible for tooth support and the mechanical properties of the periodontal ligament (PDL) remain a subject of considerable controversy. In the past, various experimental techniques and theoretical analyses have been employed to tackle this intricate problem. The aim of this study was to investigate the viscoelastic behaviors of the PDL using three-dimensional finite element analysis. METHODS: Three dentoalveolar complex models were established to simulate the tissue behaviors of the PDL: (1) deviatoric viscoelastic model; (2) volumetric viscoelastic model; and (3) tension-compression volumetric viscoelastic model. These modified models took into consideration the presence of tension and compression along the PDL during both loading and unloading. The inverse parameter identification process was developed to determine the mechanical properties of the PDL from the results of previously reported in vitro and in vivo experiments. RESULTS: The results suggest that the tension-compression volumetric viscoelastic model is a good approximation of normal PDL behavior during the loading-unloading process, and the deviatoric viscoelastic model is a good representation of how a damaged PDL behaves under loading conditions. Moreover, fluid appears to be the main creep source in the PDL. CONCLUSION: We believe that the biomechanical properties of the PDL established via retrograde calculation in this study can lead to the construction of more accurate extra-oral models and a comprehensive understanding of the biomechanical behavior of the PDL.

[Differential invasion and metastasis capacities of methotrexate enantiomer-resistant A549 cell lines].

OBJECTIVE: To study the differential in vitro motor and invasion capacities of methotrexate (MTX) enantiomer-resistant tumor cells. METHODS: The incremental concentrations and successive low-dose induction were employed to acquire the cell series resistant to 15 µmol/L MTX enantiomer, namely L-(+)-MTX/A549 and D-(-)-MTX/A549. Their drug-resistant indices were determined by MTT assay and their migration capacities by wound healing assay. Double soft-agar clone formation was used to detect the colony efficiency and size. And Transwell was employed to detect the in vitro movement and invasion capacity of three cell types. RESULTS: The resistance indices of L-(+)-MTX/A549 and D-(-)-MTX/A549 were (6.1 ± 1.0) and (20.3 ± 1.8) respectively. At 72 hours after wound healing assay, the number of L-(+)-MTX/A549 entering scratch zone was fewer than that of D-(-)-MTX/A549; The numbers of colony formation in D-(-)-MTX/A549, L-(+)-MTX/A549 and parental cells were (50 ± 7), (44 ± 6), (52 ± 7) and the rates of colony formation (1.68% ± 0.23%), (1.49% ± 0.18%), (1.73% ± 0.23%) respectively. And there was no significant significance among three groups (P > 0.05). But the size of D-(-)-MTX/A549 was larger than that of L-(+)-MTX/A549. Transwell detected infiltration and invasion through artificial basement membrane Matrigel. The numbers of D-(-)-MTX/A549, L-(+)-MTX/A549 and parent cells were (267 ± 30), (106 ± 16) and (134 ± 16) respectively. The data were significant between D-(-)-MTX/A549 cells and L-(+)-MTX/A549 or parent cells (P < 0.05) but not significant between L-(+)-MTX/A549 and parent cells (P > 0.05). CONCLUSION: The D-(-)-MTX-induced NSCLC A549 cells have greater motor and invasion capacities than those of L-(+)-MTX-induced ones. It suggests that MTX enantiomer has different capacities of tumor invasion and metastasis after acquiring resistance.