Clinical and histological features of patients with chronic hepatitis B virus infection in the grey zone.

Chronic HBV infection patients who do not conform to any of the usual immune states are regarded as 'grey zone' patients. We aimed to investigate the proportion of chronic HBV infection patients in the grey zone, and evaluate the clinical characteristics and liver pathological changes in grey zone patients. Clinical data of 1391 treatment-naive chronic HBV infection patients with liver biopsy were collected. Natural history of HBV infection was determined based on European Association for the Study of the Liver (EASL) 2017, American Association for the Study of Liver Diseases (AASLD) 2018 and Chinese 2019 guidelines for the prevention and treatment of chronic HBV infection. Significant liver histological changes and associated risk factors of normal ALT grey zone patients were analysed. According to EASL, AASLD and Chinese criteria, there were 50.0%, 28% and 37.4% chronic HBV infection patients in the grey zone. Among the 353 grey zone patients with normal ALT, 72.4% had significant liver histological changes. ALT (optimal cut-off value 25 IU/L) and HBV DNA (optimal cut-off value 18,000 IU/mL) were independent risk factors of significant liver histological abnormalities. In conclusion, a substantial proportion of grey zone patients with normal ALT have significant liver histological changes that can be predicted by levels of serum ALT and HBV DNA. These results provide guidance of antiviral treatment in grey zone patients.

Tofu by-product soy whey substitutes urea: Reduced ammonia volatilization, enhanced soil fertility and improved fruit quality in cherry tomato production.

Soy whey is an abundant, nutrient-rich and safe wastewater produced in tofu processing, so it is necessary to valorize it instead of discarding it as sewage. Whether soy whey can be used as a fertilizer substitute for agricultural production is unclear. In this study, the effects of soy whey serving as a nitrogen source to substitute urea on soil NH3 volatilization, dissolved organic matter (DOM) components and cherry tomato qualities were investigated by soil column experiment. Results showed that the soil NH4+-N concentrations and pH values of the 50% soy whey fertilizer combined with 50% urea (50%-SW) and 100% soy whey fertilizer (100%-SW) treatments were lower than those of 100% urea treatment (CKU). Compared with CKU, 50%-SW and 100%-SW treatments increased the abundance of ammonia oxidizing bacteria (AOB) by 6.52-100.89%, protease activity by 66.22-83.78%, the contents of total organic carbon (TOC) by 16.97-35.64%, humification index (HIX) of soil DOM by 13.57-17.99%, and average weight per fruit of cherry tomato by 13.46-18.56%, respectively. Moreover, soy whey as liquid organic fertilizer reduced the soil NH3 volatilization by 18.65-25.27% and the fertilization cost by 25.94-51.87% compared with CKU. This study provides a promising option with economic and environmental benefits for soy whey utilization and cherry tomato production, which contributes to the win-win effectiveness of sustainable production for both the soy products industry and agriculture.

Fluoxetine attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage: a possible role for the regulation of TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Neuroinflammation is closely associated with functional outcome in subarachnoid hemorrhage (SAH) patients. Our recent study demonstrated that fluoxetine inhibited NLRP3 inflammasome activation and attenuated necrotic cell death in early brain injury after SAH, while the effects and potential mechanisms of fluoxetine on neuroinflammation after SAH have not been well-studied yet. METHODS: One hundred and fifty-three male SD rats were subjected to the endovascular perforation model of SAH. Fluoxetine (10 mg/kg) was administered intravenously at 6 h after SAH induction. TAK-242 (1.5 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h after SAH. SAH grade, neurological scores, brain water content, Evans blue extravasation, immunofluorescence/TUNEL staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were performed. RESULTS: Fluoxetine administration attenuated BBB disruption, brain edema, and improved neurological function after SAH. In addition, fluoxetine alleviated the number of Iba-1-positive microglia/macrophages, neutrophil infiltration, and cell death. Moreover, fluoxetine reduced the levels of pro-inflammatory cytokines, downregulated the expression of TLR4 and MyD88, and promoted the nuclear translocation of NF-κB p65, which were also found in rats with TAK-242 administration. Combined administration of fluoxetine and TAK-242 did not enhance the neuroprotective effects of fluoxetine. CONCLUSION: Fluoxetine attenuated neuroinflammation and improved neurological function in SAH rats. The potential mechanisms involved, at least in part, TLR4/MyD88/NF-κB signaling pathway.

[Hypoglossal canal dural arteriovenous fistulas treated with transvenous embolization:report of two cases and literature review].

Two cases of hypoglossal canal dural arteriovenous fistulas (HCDAVF) were reported. The clinical manifestation, radiological features, treatment and prognosis were reviewed. Both cases presented chemosis and pulsatile tinnitus. 3D-time-of-flight (TOF) magnetic resonance angiography (MRA) demonstrated abnormal high signal in hypoglossal canal. Cerebral digital subtraction angiography (DSA) showed that these HCDAVFs were supplied by multiple intracranial and extracranial arteries, and fistulas were located in hypoglossal canal. Fistulas were blocked by coils and Onyx-18 through transvenous approach, and the angiography after the embolism showed complete occlusion of fistula. No adverse events after treatment and no recurrence during the follow up were observed.

Melatonin attenuates neurogenic pulmonary edema via the regulation of inflammation and apoptosis after subarachnoid hemorrhage in rats.

Neurogenic pulmonary edema (NPE) is a serious non-neurological complication that can occur after a subarachnoid hemorrhage (SAH) and is associated with decreased survival and a poor neurological outcome. Melatonin is a strong antioxidant that has beneficial effects against SAH in rats, including reduced mortality and reduced neurological deficits. The molecular mechanisms underlying these clinical effects in the SAH model, however, have not been clearly identified. This study was undertaken to determine the influence of melatonin on SAH-induced NPE and the potential mechanism of these effects using the filament perforation model of SAH in male Sprague Dawley rats. Either melatonin (150 mg/kg) or a vehicle was given via an intraperitoneal injection 2 hr after an SAH induction. Lung samples were extracted 24 hr after SAH. The results show that the melatonin treatment attenuated SAH-induced NPE by preventing alveolar-capillary barrier dysfunctions via inhibiting the disruption of tight junction proteins (ZO-1 and occludin). Moreover, the treatment downregulated the levels of mature interleukin (IL) -1ß, myeloperoxidase (MPO), and matrix metallopeptidase (MMP) 9 expression/activation, which were increased in the lung; also, melatonin treatment improved neurological deficits. Furthermore, the melatonin treatment markedly reduced caspase-3 activity and the number of TUNEL-positive cells in the lung. Taken together, these findings show that administration of melatonin attenuates NPE by preventing alveolar-capillary barrier dysfunctions via repressing the inflammatory response and by anti-apoptosis effects after SAH.

Melatonin attenuates inflammatory response-induced brain edema in early brain injury following a subarachnoid hemorrhage: a possible role for the regulation of pro-inflammatory cytokines.

Melatonin is a strong anti-oxidant that has beneficial effects against early brain injury (EBI) following a subarachnoid hemorrhage (SAH) in rats; protection includes the reduction of both mortality and neurological deficits. The molecular mechanisms underlying these clinical effects in the SAH model have not been clearly identified. This study examined the influence of melatonin on brain edema secondary to disruption of the blood-brain barrier (BBB) and the relationship between these effects and pro-inflammatory cytokines in EBI following SAH using the filament perforation model of SAH in male Sprague-Dawley rats. Melatonin (150 mg/kg) or vehicle was given via an intraperitoneal injection 2 hr after SAH induction. Brain samples were extracted 24 hr after SAH. Melatonin treatment markedly attenuated brain edema secondary to BBB dysfunctions by preventing the disruption of tight junction protein expression (ZO-1, occludin, and claudin-5). Melatonin treatment also repressed cortical levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), which were increased in EBI 24 hr after SAH. To further identify the mechanism of this protection, we demonstrated that administration of melatonin attenuated matrix metallopeptidase 9 expression/activity and vascular endothelial growth factor expression, which are related to the inflammatory response and BBB disruption in EBI after SAH. Taken together, this report shows that melatonin prevents disruption of tight junction proteins which might play a role in attenuating brain edema secondary to BBB dysfunctions by repressing the inflammatory response in EBI after SAH, possibly associated with regulation of pro-inflammatory cytokines.

Intraventricular haemorrhage treated by extra ventricular drainage with catheter mistakenly penetrating the cisterna ambiens: A case report.

Intraventricular haemorrhage (IVH) is a severe and acute type of stroke with a complex pathophysiology and is a therapeutic challenge. This case report described a man in his early 50's diagnosed with IVH by computed tomography (CT). Although bilateral extraventricular drainage (EVD) was undertaken, a postoperative CT scan showed that while the left catheter was correctly positioned, the right catheter had been wrongly inserted into the cisterna ambiens. The procedure was equivalent to simultaneous EVD combined with cisternostomy. As a consequence, the haematoma was rapidly removed, the risk of infection and long-term hydrocephalus was reduced, and prognosis was improved. Large case-control studies or prospective studies are needed to evaluate the safety and effectiveness of this treatment modality.

[Effects of Straw and Fertilizer Managements on Nitrogen Loss in Rice Cultivation in Taihu Lake Basin].

Nitrogen loss from rice systems is an important source of agricultural non-point source pollution. Many studies revolve around reducing the rate of nitrogen fertilizer application. However, studies examining the characteristics of nitrogen loss in multiple loss paths （runoff, leaching, and lateral seepage） under different straw and fertilizer managements are lacking. Therefore, a study was carried out based on a rice field planted for more than 20 years with straw continuously returned to the field for more than 5 years in Taihu lake basin. The effects of straw and fertilizer managements on nitrogen loss in different paths during the whole growth period of rice were studied. Moreover, straw and fertilizer managements were evaluated by their production suitability and environmental friendliness based on crop yield, nitrogen use efficiency, and nitrogen loss. The results showed that straw removal from the field increased the response sensitivity of nitrogen accumulation in plant tissue to nitrogen application. The nitrogen loss in the rice season was 9-17 kg·hm-2, accounting for 5%-7% of the nitrogen application rate. Straw removal increased the risk of nitrogen loss when soaking water discharged. Straw returning could decrease the nitrogen loss by more than 15%, though the effect of straw on nitrogen loss via lateral seepage was not clear. Furthermore, the suitable substitution of organic fertilizer （30% in this study） could respectively reduce the amount of nitrogen loss via runoff, leaching, and lateral seepage by 16%, 26%, and 37% compared with the fertilizer application under the same nitrogen gradient. In conclusion, the implementation of straw returning and fertilizer type optimization measures effectively reduced the nitrogen loss for unit weight of rice production and realized the balance between agricultural production and environmental protection.

'An eye for an eye' therapeutic strategy for cavernous sinus dural arteriovenous fistula: a single-center experience.

BACKGROUND: In cavernous sinus dural arteriovenous fistulas (CS-DAVF), ophthalmological symptoms are usually the main clinical presentation, caused by abnormal drainage of the superior ophthalmic vein (SOV). Early opacification of the SOV during cerebral angiography inevitably signifies the fistula's shunt point at the confluence of the SOV and CS. We aimed to leverage this anatomical feature to achieve precise embolization, thereby enhancing the embolization success rate and preventing CS-related symptoms and complications resulting from overpacking. METHODS: This single-center, case series study was conducted between May 2017 and September 2023, and included the largest sample of CS-DAVF patients treated via the transfemoral vein-SOV approach. We retrospectively reviewed the data of 32 CS-DAVF patients with inferior petrosal sinus (IPS) occlusion. RESULTS: The study demonstrated an excellent immediate postoperative complete embolization rate (31/32, 97%). Only three patients (3/32, 9%) developed temporary endovascular treatment-related complications. The average operation time was 131.6±61.6 min, with an average of 1.2±1.1 coils and 1.8±1.2 mL Onyx glue used per patient. CS-DAVF-associated ophthalmological symptoms resolved in all patients. We also identified a rare anatomical variation, where 77% of the patients had a facial vein draining into the external jugular vein. CONCLUSIONS: Transfemoral vein-SOV embolization should be considered a crucial alternative approach in CS-DAVF patients with occluded IPS and predominantly SOV drainage. This approach showed an excellent immediate postoperative complete embolization rate and satisfactory long-term outcomes along with clinical safety. We therefore strongly advocate for this 'an eye for an eye' treatment strategy.

TIMP1 protects against blood-brain barrier disruption after subarachnoid haemorrhage by inhibiting ubiquitination of astrocytic ß1-integrin.

BACKGROUND: Astrocytes regulate blood-brain barrier (BBB) integrity, whereas subarachnoid haemorrhage (SAH) results in astrocyte dysregulation and BBB disruption. Here, we explored the involvement of tissue inhibitor of matrix metalloprotease-1 (TIMP1) in astrocyte-mediated BBB protection during SAH, along with its underlying mechanisms. METHODS: C57BL/6J mice were used to establish a model of SAH. The effects of TIMP1 on SAH outcomes were analysed by intraperitoneal injection of recombinant mouse TIMP1 protein (rm-TIMP1; 250 µg/kg). The roles of TIMP1 and its effector ß1-integrin on astrocytes were observed by in vivo transduction with astrocyte-targeted adeno-associated virus carrying TIMP1 overexpression plasmid or ß1-integrin RNAi. The molecular mechanisms underlying TIMP1 and ß1-integrin interactions were explored in primary cultured astrocytes stimulated with red blood cells (RBCs). RESULTS: TIMP1 was upregulated after SAH. Administration of rm-TIMP1 mitigated SAH-induced early brain injury (EBI) in male and female mice. TIMP1 was primarily expressed in astrocytes; its overexpression in astrocytes led to increased ß1-integrin expression in astrocytes, along with the preservation of astrocytic endfoot attachment to the endothelium and subsequent recovery of endothelial tight junctions. All of these effects were reversed by the knockdown of ß1-integrin in astrocytes. Molecular analysis showed that TIMP1 overexpression decreased the RBC-induced ubiquitination of ß1-integrin; this effect was partially achieved by inhibiting the interaction between ß1-integrin and the E3 ubiquitin ligase Trim21. CONCLUSION: TIMP1 inhibits the interaction between ß1-integrin and Trim21 in astrocytes, thereby rescuing the ubiquitination of astrocytic ß1-integrin. It subsequently restores interactions between astrocytic endfeet and the endothelium, as well as BBB integrity, eventually mitigating SAH-induced EBI.

LRIG1 dictates the chemo-sensitivity of temozolomide (TMZ) in U251 glioblastoma cells via down-regulation of EGFR/topoisomerase-2/Bcl-2.

In the current study, we aimed to understand the potential role of leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) in TMZ-resistance of U251 glioma cells. We established TMZ-resistant U251 clones (U251/TMZ cells), which expressed low level of LRIG1, but high levels of epidermal growth factor receptor (EGFR), topoisomerase-2 (Topo-2) and Bcl-2. Depletion of LRIG1 by the targeted RNA interference (RNAi) upregulated EGFR/Topo-2/Bcl-2 in U251 cells, and the cells were resistant to TMZ. Reversely, over-expression of LRIG1 in U251 cells downregulated EGFR/Topo-2/Bcl-2 expressions, and cells were hyper-sensitive to TMZ. Our data suggested EGFR-dependent mammalian target of rapamycin (mTOR) activation was important for Topo-2 and Bcl-2 expressions in U251/TMZ cells. The EGFR inhibitor and the mTOR inhibitor downregulated Topo-2/Bcl-2 expressions, both inhibitors also restored TMZ sensitivity in U251/TMZ cells. Finally, inhibition of Topo-2 or Bcl-2 by targeted RNAi(s) knockdown or by the corresponding inhibitor re-sensitized U251/TMZ cells to TMZ, indicating that both Topo-2 and Bcl-2 were important for TMZ resistance in the resistant U251 cells. Based on these results, we concluded that LRIG1 inhibits EGFR expression and the downstream signaling activation, interferes with Bcl-2/Topo-2 expressions and eventually sensitizes glioma cells to TMZ.

The comparison between dissociate bone flap cranioplasty and traditional cranioplasty in the treatment of depressed skull fractures.

OBJECTIVE: Depressed skull fractures (DSF) with operation indications should be paid with enough attention because they have several complications and can influence esthetics. The optimal surgical method for DSF remains unclear. We explored the merits of dissociate bone flap cranioplasty. PATIENTS AND METHODS: From July 2006 to August 2012, we performed 30 craniotomies on patients with DSF, which were divided into 2 groups: 1 group, which consisted of 18 patients, underwent dissociate bone cranioplasty; the other 12 patients underwent lever-up cranioplasty. A helical computed tomographic scan was routinely obtained after the operation and a 3-dimensional technique was performed on some patients to evaluate the postoperative condition of the flap. RESULTS: Dissociate bone flap cranioplasty was performed on the 18 patients [11 men, 7 women: age, 26-70 (41) y]. No complications were observed in these patients. Lever-up cranioplasty was applied in the 12 patients [8 men, 4 women: age, 19-60 (41.8) y]; 2 patients had wound infection and 2 emerged with epidural hematoma. Obvious statistical significance of stability (P = 0.013) and position (P = 0.015) was found between the 2 methods. CONCLUSIONS: Dissociate bone flap cranioplasty is safer, more flexible, has less complications, and has better plasticity. We advocate the use of bone flap cranioplasty in dealing with DSF.

Berberine mitigates intracerebral hemorrhage-induced neuroinflammation in a gut microbiota-dependent manner in mice.

BACKGROUND: Neuroinflammation is a frequent cause of brain damage after intracerebral hemorrhage (ICH). Gut microbiota are reported to regulate neuroinflammation. Berberine has been found to have anti-inflammatory actions, including in the central nervous system. However, it is not known whether berberine regulates neuroinflammation after ICH, nor is the relationship between the antineuroinflammatory actions of berberine and the gut microbiota after ICH understood. METHODS: ICH was induced in male mice by collagenase injection. Immunofluorescent staining and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect microglia/macrophage phenotypes. Immunofluorescent staining, ELISA, and FITC-dextran were conducted to determine gut function. 16S rRNA sequencing of the fecal material was conducted to determine alterations in the gut microbiota. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) were used to deplete or restore the gut microbiota, respectively. Cylinder, forelimb placement and wire hanging tests were conducted to evaluate neurobehavioral function. RESULTS: Berberine significantly reduced neuroinflammation and alleviated neurological dysfunction by preventing microglial/macrophage proinflammatory polarization in ICH mice. Berberine also enhanced the function of the intestinal barrier, as shown by reductions in the levels of lipopolysaccharide-binding protein. Neuroinflammation in ICH mice was markedly reduced after transplantation of microbiota from berberine-treated mice, similar to treatment with oral berberine. In addition, a reduction in the microbiota reversed the neuroprotective effect of berberine. CONCLUSIONS: Berberine is a potential treatment for ICH-induced neuroinflammation, and its effects are at least partially dependent on the gut microbiota.

[Effects of Aeration on Surface Water Nutrient Dynamics and Greenhouse Gas Emission in Different Straw Returning Paddy Fields].

Straw returning is of great significance for improving soil structure, soil fertility, crop yield, and quality. However, straw returning causes environmental problems such as increased methane emission and non-point source pollutant emission risk. How to reduce the negative effects of straw returning is an urgent problem to be solved.In this study, the effects of aerobic treatment on carbon and nitrogen concentration in surface water and greenhouse gas emissions in paddy fields with different treatments of straw returning were systematically compared.The results showed that different treatments of straw returning significantly increased chemical oxygen demand (COD) in the surface water of the paddy field and significantly promoted the methane emission of the rice field and the global warming potential (GWP), although it slightly reduced N2O emission. The increasing trends showed that wheat straw returning>rape straw>broad bean straw returning.Straw returning increased rice yield when compared with the control without straw returning, but the difference was not significant. Aerobic treatment reduced the COD in surface water by 15%-32%, the methane emission of the paddy field by 10.4%-24.8%, and the GWP of paddy field by 9.7%-24.4% under different straw returning treatments, without affecting the rice yield. The mitigation effect of aerobic treatment with wheat straw returning was the best. The results indicated the potential of oxygenation measures in greenhouse gas emission mitigation and COD emission risk reduction in straw returning paddy fields, especially in wheat straw returning paddy fields.

The potential effect of HBV vaccination on off-treatment HBsAg reversion after interferon-induced HBsAg clearance.

Off-treatment HBsAg reversion occurs in a considerable number of chronic hepatitis B(CHB) patients after IFN(interferon)-induced HBsAg clearance. HBV vaccination protects the general population against HBV infection. However, it remains unclear whether HBV vaccination could prevent off-treatment HBsAg reversion in CHB patients with HBsAg clearance. CHB patients (n = 199) with HBsAg clearance were included in the current study, comprising spontaneous HBsAg clearance group (n = 51), NA (nucleoside/nucleotide analogues)-induced group (n = 36) and IFN-induced group (n = 112). Log-rank test was performed to compare the cumulative incidences of HBsAg reversion between groups. Cox regression model was used to identify the factors associated with off-treatment HBsAg reversion. The 5-year cumulative incidence of HBsAg reversion in IFN-induced group was significantly higher than that in NA-induced group or spontaneous group (27.6% vs. 3.3% vs. 8.1%, both p < .05). In IFN-induced group, 66.7% of CHB patients received HBV vaccination. The cumulative incidence of HBsAg reversion in individuals with strong responses to HBV vaccination (HBsAb level >100mIU/ml) was significantly lower than that in those with weak responses to HBV vaccination (HBsAb level ≤100mIU/ml) or without HBV vaccination in IFN-induced group (7.7% vs. 58.5% vs. 31.9%, both p < .05). Multivariate Cox regression analysis confirmed strong responses to HBV vaccination were independently associated with a lower cumulative incidence of HBsAg reversion after IFN-induced HBsAg clearance (HR = 0.246, 95%CI: 0.066-0.907, p = .035). HBV vaccination has potential to prevent off-treatment HBsAg reversion in CHB patients after IFN-induced HBsAg clearance via a sufficiently high level of HBsAb, helping clinicians optimize the clinical management of such patients.

Clinic-radiomics model using liver magnetic resonance imaging helps predict chronicity of drug-induced liver injury.

BACKGROUND AND AIMS: Some drug-induced liver injury (DILI) cases may become chronic, even after drug withdrawal. Radiomics can predict liver disease progression. We established and validated a predictive model incorporating the clinical characteristics and radiomics features for predicting chronic DILI. METHODS: One hundred sixty-eight DILI patients who underwent liver gadolinium-diethylenetriamine pentaacetate-enhanced magnetic resonance imaging were recruited. The patients were clinically diagnosed using the Roussel Uclaf causality assessment method. Patients who progressed to chronicity or recovery were randomly divided into the training (70%) and validation (30%) cohorts, respectively. Hepatic T1-weighted images were segmented to extract 1672 radiomics features. Least absolute shrinkage and selection operator regression was used for feature selection, and Rad-score was constructed using support vector machines. Multivariable logistic regression analysis was performed to build a clinic-radiomics model incorporating clinical characteristics and Rad-scores. The clinic-radiomics model was evaluated for its discrimination, calibration, and clinical usefulness in the independent validation set. RESULTS: Of 1672 radiomics features, 28 were selected to develop the Rad-score. Cholestatic/mixed patterns and Rad-score were independent risk factors of chronic DILI. The clinic-radiomics model, including the Rad-score and injury patterns, distinguished chronic from recovered DILI patients in the training (area under the receiver operating characteristic curve [AUROC]: 0.89, 95% confidence interval [95% CI]: 0.87-0.92) and validation (AUROC: 0.88, 95% CI: 0.83-0.91) cohorts with good calibration and great clinical utility. CONCLUSION: The clinic-radiomics model yielded sufficient accuracy for predicting chronic DILI, providing a practical and non-invasive tool for managing DILI patients.

Characterization of Chromatin Accessibility in Fetal Bovine Chondrocytes.

Despite significant advances of the bovine epigenome investigation, new evidence for the epigenetic basis of fetal cartilage development remains lacking. In this study, the chondrocytes were isolated from long bone tissues of bovine fetuses at 90 days. The Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq) were used to characterize gene expression and chromatin accessibility profile in bovine chondrocytes. A total of 9686 open chromatin regions in bovine fetal chondrocytes were identified and 45% of the peaks were enriched in the promoter regions. Then, all peaks were annotated to the nearest gene for Gene Ontology (GO) and Kyoto Encylopaedia of Genes and Genomes (KEGG) analysis. Growth and development-related processes such as amide biosynthesis process (GO: 0043604) and translation regulation (GO: 006417) were enriched in the GO analysis. The KEGG analysis enriched endoplasmic reticulum protein processing signal pathway, TGF-ß signaling pathway and cell cycle pathway, which are closely related to protein synthesis and processing during cell proliferation. Active transcription factors (TFs) were enriched by ATAC-seq, and were fully verified with gene expression levels obtained by RNA-seq. Among the top50 TFs from footprint analysis, known or potential cartilage development-related transcription factors FOS, FOSL2 and NFY were found. Overall, our data provide a theoretical basis for further determining the regulatory mechanism of cartilage development in bovine.

DJ-1 Alleviates Neuroinflammation and the Related Blood-Spinal Cord Barrier Destruction by Suppressing NLRP3 Inflammasome Activation via SOCS1/Rac1/ROS Pathway in a Rat Model of Traumatic Spinal Cord Injury.

DJ-1 has been shown to play essential roles in neuronal protection and anti-inflammation in nervous system diseases. This study aimed to explore how DJ-1 regulates neuroinflammation after traumatic spinal cord injury (t-SCI). The rat model of spinal cord injury was established by the clamping method. The Basso, Beattie, Bresnahan (BBB) score and the inclined plane test (IPT) were used to evaluate neurological function. Western blot was then applied to test the levels of DJ-1, NLRP3, SOCS1, and related proinflammatory factors (cleaved caspase 1, IL-1ß and IL-18); ROS level was also examined. The distribution of DJ-1 was assessed by immunofluorescence staining (IF). BSCB integrity was assessed by the level of MMP-9 and tight junction proteins (Claudin-5, Occludin and ZO-1). We found that DJ-1 became significantly elevated after t-SCI and was mainly located in neurons. Knockdown of DJ-1 with specific siRNA aggravated NLRP3 inflammasome-related neuroinflammation and strengthened the disruption of BSCB integrity. However, the upregulation of DJ-1 by Sodium benzoate (SB) reversed these effects and improved neurological function. Furthermore, SOCS1-siRNA attenuated the neuroprotective effects of DJ-1 and increased the ROS, Rac1 and NLRP3. In conclusion, DJ-1 may alleviate neuroinflammation and the related BSCB destruction after t-SCI by suppressing NLRP3 inflammasome activation by SOCS1/Rac1/ROS pathways. DJ-1 shows potential as a feasible target for mediating neuroinflammation after t-SCI.

Safety and Efficacy of Tirofiban in Severe Ischemic Stroke Patients Undergoing Mechanical Thrombectomy.

Tirofiban has recently shown encouraging efficacy and safety among acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT). However, the benefits of tirofiban varied among studies depending on the patient's condition, which was often not well analyzed. This study aimed to identify the characteristics of patients who may obtain the largest benefits from tirofiban. The efficacy endpoint was a favorable outcome defined as a modified Rankin Scale (mRS) score of 0~2 at 90 days. The safety endpoints were intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Adjusted logistic regression analysis and subgroup analyses were utilized to investigate the factors associated with tirofiban and the outcome. All of 285 patients fit the inclusion criteria. Tirofiban was associated with a higher rate of favorable outcome (aOR 2.033, 95% CI, 1.002~4.123, p = 0.043) but not with an increased risk of ICH, sICH or mortality (p > 0.05). Moreover, subgroup analyses revealed that tirofiban was associated with favorable outcomes in patients with NIHSS > 14 (aOR 2.778, 95% CI 1.056~7.356, p = 0.038) but not in patients with NIHSS ≤ 14 (aOR 1.719, 95% CI 0.646~4.578, p = 0.278). No significant heterogeneity was found in the effect of tirofiban across the subgroups of age, sex, ASPECTS, time from onset to puncture, use of t-PA or stroke etiology (p for interaction > 0.05). The administration of tirofiban was associated with favorable outcomes in severe ischemic stroke patients, and further studies are needed to confirm this finding.

Single-Institute Experience of Bypass Surgery for Complex Anterior Cerebral Artery Aneurysms: Paying Special Attention to the Spatial and Diameter Relationship Between the Efferent Arteries.

OBJECTIVE: To present a retrospective review of a single-institute experience with bypass surgery of complex anterior cerebral artery aneurysm. METHODS: Eight patients (5 females and 3 males; mean age, 34.2 years) with complex anterior cerebral artery aneurysms were treated with bypass. There were 3 precommunicating aneurysms, 1 communicating artery aneurysm, and 4 postcommunicating aneurysms (2 in A2 and 2 in A3). A3-A3 side-to-side in situ bypass was performed in 6 cases. A3-radial artery-A3 interpositional bypass was performed in 1 case with A3 segments located far apart, and A3-A3 transplantation was performed in 1 case with nonparallel aligned A3 segments. Of the 8 aneurysms, 3 were secured with proximal clipping, 1 was secured with distal clipping, 1 was secured with direct clipping, 1 was secured with isolation, and 2 were secured with embolization. RESULTS: Aneurysm obliteration was achieved in all cases. Only 1 in situ bypass from a smaller donor artery to a larger recipient artery failed with minor postoperative infarction. Intraoperative bleeding from the site of anastomosis occurred in 1 case during embolization. All patients had complete recovery with normal neurological function during follow-up at outpatient clinics. CONCLUSIONS: We established a simplified surgical algorithm for complex anterior cerebral artery aneurysms based on the geometrical and spatial relationship between efferent arteries. The reasons for bypass failure and hemorrhagic complication were also discussed.