Directed Greybox Fuzzing with Stepwise Constraint Focusing

Dynamic data flow analysis has been widely used to guide greybox fuzzing. However, traditional dynamic data flow analysis tends to go astray in the massive path tracking and requires to process a large volume of data, resulting in low efficiency in reaching the target location. In this paper, we propose a directed greybox fuzzer based on dynamic constraint filtering and focusing (CONFF). First, all path constraints are tracked, and those with high priority are filtered as the next solution targets. Next, focusing on a single path constraint to be satisfied, we obtain its data condition and probe the mapping relationship between it and the input bytes through multi-byte mapping and single-byte mapping. Finally, various mutation strategies are utilized to solve the path constraint currently focused on, and the target location of the program is gradually approached through path selection. The CONFF fuzzer can reach a specific location faster in the target program, thus efficiently triggering the crash. We designed and implemented a prototype of the CONFF fuzzer and evaluated it with the LAVA-1 dataset and some real-world vulnerabilities. The results show that the CONFF fuzzer can reproduce crashes on the LAVA-1 dataset and most of the real-world vulnerabilities. For most vulnerabilities, the CONFF fuzzer reproduced the crashes with significantly reduced time compared to state-of-the-art fuzzers. On average, the CONFF fuzzer was 23.7x faster than the state-of-the-art code coverage-based fuzzer Angora and 27.3x faster than the classical directed greybox fuzzer AFLGo

Effects of Non-invasive Positive Pressure Ventilation on Sleep of Patients in Respiratory Intensive Care Unit Assessed by Overnight Polysomnography

BackgroundSleep disorders are commonin RICU patients, with mechanical ventilation as one of the important factors leading to sleep disorders in RICU patients. Previous studies have mainly focused on the effect of invasive positive pressure ventilation (IPPV) on sleep in RICU patients, but there is no study on the effect of polysomnography on sleep in RICU patients with non-invasive positive pressure ventilation (NIPPV) .ObjectiveTo evaluate patients' sleep disorders and the effect of NIPPV on sleep in patients in respiratory intensive care unitsby overnight polysomnography.MethodsThe clinical data of 31 patients who underwent overnight polysomnography in the Department of Respiratory and Critical Care Medicine of Peking University First Hospital from May 2012 to August 2021 were retrospectively analyzed. The clinical data〔sex, age, height, body mass index, APACHEⅡscore, underlying diseases, main diagnosis, white blood cell count, hemoglobin, serum albumin, high-sensitivity C-reactive protein (hs-CRP) , arterial blood gas analysis, respiratory failure classification, total length of hospital stay, length of stay in RICU, RICU stay in the past 6 months, death during hospitalization〕, sleep characteristics 〔respiratory events: apnea-hypopnea index (AHI) , respiratory disturbance index (RDI) , total detection time, total sleep time, sleep latency, sleep efficiency, sleep stage: time, latency and proportion of REM and NREM, pulse oxygen: minimum pulse oxygen, average pulse oxygen during sleep, heart rate: minimum heart rate, maximum heart rate〕 of patients were collected. The patients were divided into NIPPV group and control group (non-NIPPV group) according to whether NIPPV treatment was performed during overnight polysomnography, and the clinical data and sleep characteristics of the two groups were compared.ResultsThere were 15 cases in the NIPPV group and 16 cases in the control group. Compared with the control group, the total sleep time (P=0.028) , REM sleep time (P=0.034) , NREM time (P=0.003) and N2 sleep time (P=0.003) were shortened in the NIPPV group, while the sleep efficiency (P=0.038) decreased, and the average heart rate increased (P=0.028) .ConclusionSleep disturbance is a common problem in RICU patients, and NIPPV patients are more likely to lead to decreased total sleep time, decreased REM sleep, and decreased sleep efficiency. It is recommended that RICU patients be routinely assessed with overnight polysomnography and given appropriate intervention to conduct appropriate interventions

The Effect of Mechanical Ventilation on TASK-1 Expression in the Brain in a Rat Model

Background and Objective. TWIK-related acid-sensitive potassium channel 1 (TASK-1) is closely related to respiratory central control and neuronal injury. We investigated the effect of MV on TASK-1’s functions and explored the mechanism using a rat model. Methods. Male Sprague-Dawley rats were randomized to three groups: (1) high tidal volume (HVt): MV for four hours with Vt at 10 mL/kg; (2) low Vt (LVt): MV for four hours with Vt at 5 mL/kg; (3) basal (BAS): anesthetized and unventilated animals. We measured lung histology and plasma and brain levels of proteins (IL-6, TNF-α, and S-100B) and determined TASK-1 levels in rat brainstems as a marker of respiratory centre activity. Results. The LISs (lung injury scores) were significantly higher in the HVt group. Brain inflammatory cytokines levels were different to those in serum. TASK-1 levels were significantly lower in the MV groups (P=0.002) and the HVt group tended to have a lower level of TASK-1 than the LVt group. Conclusion. MV causes not only lung injury, but also brain injury. MV affects the regulation of the respiratory centre, perhaps causing damage to it. Inflammation is probably not the main mechanism of ventilator-related brain injury

CXCR4/Let-7a Axis Regulates Metastasis and Chemoresistance of Pancreatic Cancer Cells Through Targeting HMGA2

Background/Aims: Pancreatic cancer cells (PCC) is one of the most risky cancers and gemcitabine (GEM) is the standard first-line drug for treating PCC. The PCC will develop drug resistance to GEM after a period of treatment. However, the detailed molecular mechanism of pathogenesis and drug resistance remains unresolved. Methods: we employed qRT-PCR and western blot to examine the expression level of CXCR4, let-7a and HMGA2. In addition, we used MTT assay to detect cell proliferation and transwell assay to measure migration and invasiveness. The expression level of epithelial marker E-cadherin and mesenthymal marker N-cadherin was detected by western blot. The apoptosis was determined using annexin V-FITC/PI apoptosis detection kit by flow cytometry. Results: we first proved that CXCR4 negatively regulated let-7a in PCC. Next, let-7a was confirmed to play crucial role in tumorigenesis, metastasis and drug resistance of pancreatic cancer cells Bxpc-3 and Panc-1 in vitro and in vivo. Finally, we identified HMGA2 as important downsteam target of let-7a in PCC and overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of GEM inhibited by let-7a. Conlusion: Taken together, we show an important signaling pathway involved in pathogenesis and drug resistance of PCC, thereby providing deeper insight into molecular mechanism by which CXCR4/let-7a regulates tumorigenesis and drug resistance of PCC. These findings will help us develop new strategies for diagnosis and treatment of PCC

Clinical Features of Herpes Simplex Encephalitis and Risk Factors for Post-Encephalitic Epilepsy in Children

Abstract Objective Herpes simplex encephalitis (HSE) is a common form of sporadic encephalitis and is prone to neurological sequelae such as epilepsy in young children, which can have a significant impact on young children at the time of neurological development. This study aimed to analyze the clinical features of HSE in children and to explore its risk factors for post-encephalitic epilepsy (PE). Methods The case data of children who met the HSE diagnostic criteria between January 2013 and June 2021 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results The incidence of PE in children with HSE was 42.2% (19/45cases). The initial symptoms were fever with headache or convulsions. In the acute phase, there were 13 cases (28.9%) with psychiatric behavior disorders, 16 cases (35.6%) with neurological deficit symptoms, and 24 cases (53.3%) with altered consciousness. Univariate analysis of fever duration, fever peak, psychiatric behavior disorders, neurological deficit symptoms, acute phase seizures and seizure frequency, ICU length of stay, admission GCS, and cranial imaging in children with HSE indicated statistically significant mixed involvement (all P < 0.05), and multivariate logistic regression analysis suggested that repetitive seizures (more than 5 seizures) (OR = 1.551;95% CI 1.229–1.958, P < 0.001) in the acute phase was an independent risk factor for the occurrence of PE. Conclusion The main symptoms in children with HSE in the acute phase include seizures, altered consciousness, neurological deficit symptoms, and psychiatric behavioral abnormalities. Children with HSE has a high incidence of PE, especially if they have repetitive seizures (more than 5 seizures) in the acute phase

Pulmonary tuberculosis associated acute fibrinous and organizing pneumonia: A case report and literature review

Abstract Background Acute fibrinous and organizing pneumonia (AFOP) is a rare histological interstitial pneumonia pattern characterized by patches of “fibrin balls” distributed within the alveoli and organizing pneumonia. Currently, there is no consensus on the diagnosis and treatment of this disease. Methods We present the case of a 44‐year‐old male with AFOP secondary to Mycobacterium tuberculosis. We have further reviewed organizing pneumonia (OP) and AFOP caused by tuberculosis. Conclusion Tuberculosis secondary to OP or AFOP is rare and challenging to diagnose. We need to constantly adjust the treatment plan based on the patient's symptoms, test results, and response to treatment in order to arrive at an accurate diagnosis and maximize treatment efficacy

Cyclic steps along the South Taiwan Shoal and West Penghu submarine canyons on the northeastern continental slope of the South China Sea

Large-scale step-like features within the South Taiwan Shoal and West Penghu submarine canyons on the northeastern continental slope of the South China Sea are investigated by integrating high-resolution multibeam bathymetric data and multichannel seismic profiles. These step-like features, ranging from 1.2 to 10.0 km in wavelength and 5.4–80.9 m in wave height, are mostly interpreted as cyclic steps formed by turbidity currents flowing through the canyons, based on their characteristic step-like morphology, in-train alignment, large wavelengths and aspect ratios (ratio of wavelength to wave height), and typical upstream-sloping backset bedding, among others. A train of 19 continuous steps delineated along the thalweg of the South Taiwan Shoal canyon measures up to 100 km and may be the longest ever reported. Nine short trains of scours identified on a terrace of the South Taiwan Shoal canyon are oriented parallel to the distributaries draining over the terrace and roughly perpendicular to the main canyon thalweg, indicating a complicated flow pattern within the canyon valley. Two trains of scours separated by an intracanyon high in the steeper middle reach of the West Penghu canyon are interpreted as transitional bed forms between antidunes and cyclic steps, which develop downstream into a train of five net-depositional cyclic steps with typical backset bedding in the gentler-sloping lower reach of the canyon. Average slope gradients for the canyon reaches with cyclic steps range from 0.26° to 1.24°. Along each thalweg step train, a slope break is identified to separate the net-erosional cyclic steps in the steeper upstream segment from the net-depositional ones in the gentler downstream segment. Rough estimations indicate that the paleoflows are 100 to 300 m thick with maximum velocities of up to 10 m s–1. The estimated flow depths match well with those inferred from geomorphologic analysis. Estimated paleodischarges of ?7–23 × 105 m3 s–1 are equivalent to ten times the discharge of the modern Amazon River