Transcriptomic and enzymatic analysis reveals the roles of glutamate dehydrogenase in Corynebacterium glutamicum.

Glutamate dehydrogenase (Gdh), catalyzing the reversible conversion between 2-oxoglutarate and glutamate, plays an important role in the connection of nitrogen and carbon metabolism. Yet little is known about these enzymes in the amino acid-manufacturing Corynebacterium glutamicum. In the present study, we firstly identified the enzymatic characteristics of two Gdhs (GdhA and GdhB). The results showed that both GdhA and GdhB prefers NADPH as a coenzyme and have higher affinity for 2-OG than glutamate. The growth characteristics of gdhAΔ mutant and gdhBΔ mutant, gdhABΔ mutant showed GdhA serves as the main conduit for ammonium assimilation, and GdhB is the main glutamate- metabolizing enzyme in C. glutamicum. The full-genome transcriptomic analysis was used to investigate physiological response of C. glutamicum to the glutamate as nitrogen source, and gdh deletion. The results showed that the nitrogen starvation response was elicited when glutamine served as the sole nitrogen source. gdhAΔBΔ double deletion trigger a partially deregulated nitrogen starvation response, in which genes involved in nitrogen assimilation showed obviously upregulated in a certain extent. On the other hand, the genes of phosphotransferase system (PTS) and glycolysis pathway, most genes in pentose phosphate pathway were significantly upregulated, indicating that gdh deficiency initiated the enhancement of the absorption and metabolism of carbon sources. We believed that our results in this study will give new insights on the molecular mechanism of Gdh activity cross-talks with carbon and nitrogen metabolism, also setting a new background for further flux redistribution applied research of biotechnological interest.

Diastolic blood pressure predicts enlarged vertebral venous plexus and intracranial pressure in patients with bilateral transverse sinus stenosis.

Background: Bilateral transverse sinus stenosis (BTSS) is associated with intracranial hypertension. Enlarged vertebral venous plexus (EVVP) refers to a compensation mechanism against elevated intracranial pressure (ICP) in patients with BTSS. This study aims to investigate the influencing factors of EVVP. Methods: Patients with BTSS were prospectively recruited from the neurology department and neurosurgery department of Xuanwu Hospital Capital Medical University from January 2020 to December 2021. Results: A total of 37 patients were enrolled with a mean age of 45.42 ± 15.64 years. Women tend to be more susceptible to BTSS. The most common co-morbid disease was hypertension. The most common clinical manifestations were visual disorders, headaches, and tinnitus. BMI and DBP were significantly higher in BTSS patients without EVVP than those with EVVP. Multivariate analysis revealed that diastolic blood pressure (DBP) was negatively correlated with EVVP. In addition, a positive correlation between DBP and the ICP was also observed. A DBP of 81.5 mmHg was calculated as the cutoff value for the presence of EVVP. BTSS patients with DBP ≤ 81.5 mmHg had a higher incidence of EVVP and a lower ICP compared to those with DBP > 81.5 mmHg. Conclusions: DBP was identified as an independent predictor of EVVP. DBP was lower (≤81.5 mmHg) in patients with EVVP and therefore was associated with a lower ICP in patients with BTSS.

Enlarged Vertebral Venous Plexus Alleviated Intracranial Hypertension-Related Symptoms in Patients with Bilateral Transverse Sinus Stenosis.

BACKGROUND: Enlarged vertebral venous plexus (EVVP) was often observed in patients with bilateral transverse sinus stenosis (BTSS). The purpose of this study was to investigate the physiological role of EVVP in BTSS patients. METHODS: Forty-five BTSS patients and 92 normal controls were prospectively recruited from January 2014 to December 2019. The index of transverse sinus stenosis (ITSS) was used for the assessment of BTSS severity. Subjects underwent a standard lumbar puncture to measure the intracranial pressure (ICP). Papilledema and tinnitus were evaluated by using Frisén's grade and questionnaires for Tinnitus Handicap Inventory (THI), respectively. The intensity and impact of headache were assessed by using 10-point Numeric Pain Rating Scale and six-item Headache Impact Test, respectively. RESULTS: The BTSS group had more subjects with intracranial hypertension (IH) and less subjects with normal ICP than normal controls (p < 0.01; p < 0.01). BTSS patients had higher ICP than normal controls (p < 0.01). ICP was significantly lower in BTSS patients with EVVP than in those without EVVP (p < 0.01). No significant difference in ICP was found between normal controls with EVVP and those without EVVP (p = 0.99). A similar incidence of EVVP in BTSS patients and normal controls was found (p = 0.86). BTSS patients with IH exhibited a lower incidence of EVVP than those with normal ICP and overlapping ICP (p < 0.01; p < 0.01). The incidence of EVVP was not correlated with ITSS (p = 0.81). EVVP, rather than ITSS, correlated with ICP (p = 0.01). Furthermore, EVVP alleviated papilledema evaluated by Frisén's grade and tinnitus evaluated by the THI score in BTSS patients (p = 004; p = 0.02). CONCLUSIONS: EVVP in normal controls is a congenital phenomenon that exerts no impact on ICP. However, the presence of EVVP reduces ICP and alleviates IH-related papilledema and tinnitus in BTSS patients.

The role of urinary albumin-to-creatinine ratio as a biomarker to predict stroke: A meta-analysis and systemic review.

Albuminuria excretion rate, calculated as urinary albumin-to-creatinine ratio (UACR), is used clinically to evaluate albuminuria. There are different attitudes to whether high UACR predicts higher risk of stroke. The aim of this study was to evaluate the relationship between UACR and stroke. Two investigators independently searched MEDLINE, EMBASE, Cochrane Controlled Trials Register Database, Scopus and Google Scholar from January 1966 through June 2021 were screened. In addition, a manual search was conducted using the bibliographies of original papers and review articles on this topic. Two blinded reviewers abstracted the data independently to a predefined form. Among the 10,939 initially identified studies, 7 studies with 159,302 subjects were finally included. It is demonstrated that UACR predicted an increased risk of stroke using cutoff value of either 0.43 (HR, 2.39; 95% CI: 1.24 - 4.61; P <0.01), 10 mg/g (HR, 1.60; 95% CI: 1.30 - 1.97; P < 0.01) or 30 mg/g (HR, 1.84; 95% CI: 1.49 - 2.28; P < 0.01). The overall analysis confirmed that high UACR was associated with an increased rate of stroke (HR, 1.81; 95% CI: 1.52 - 2.17; P < 0.01). Furthermore, High UACR predicted higher risk of stroke in local inhabitants (HR, 1.67; 95% CI: 1.17 - 2.37; P = 0.04), adults (HR, 2.21; 95% CI: 2.07 - 2.36; P < 0.01) or elderly adults (HR, 1.96; 95% CI: 1.56 - 2.46; P < 0.01). Whereas, high UACR was unable to predict stroke in patients with either T2DM (HR, 2.25; 95% CI: 0.55 - 9.17; P = 0.26) or hypertension (HR, 0.95; 95% CI: 0.28 - 3.22; P = 0.93). Another subgroup analysis revealed that high UACR was associated with increased risk of ischemic stroke (HR, 1.60; 95% CI: 1.43 - 1.80; P < 0.01), as well as hemorrhagic stroke (HR, 1.76; 95% CI: 1.22 - 1.45; P < 0.01). In conclusion, UACR is associated with an increased risk of hemorrhagic and ischemic stroke. UACR may be used as an indicator to predict stroke in non-diabetic and non-hypertensive subjects.

Magnetic resonance black-blood thrombus imaging can confirm chronic cerebral venous thrombosis: a case report and literature review.

BACKGROUND: Cerebral venous thrombosis (CVT) is easily missed or misdiagnosed in clinical settings because of its high variability in terms of symptoms and radiological findings. Herein, we aimed to explore a promising modality for confirming presumed CVT in the hope to uncover its superior diagnostic performance to conventional imaging modalities.Case presentation: The patient complained of intolerable pain in her forehead and left eye. Her lumbar puncture opening pressure was 140 mmH2O, and her cerebrospinal fluid composition was normal. No marked abnormalities were observed in routine brain images, including non-contrast computed tomography, magnetic resonance imaging, and contrast-enhanced magnetic resonance venography. However, chronic mural thrombi in the lumen of the left cortical veins, transverse/sigmoid sinus, and superior sagittal sinus were identified in magnetic resonance black-blood thrombus imaging (MRBTI) maps. CONCLUSIONS: MRBTI can be used to directly and non-invasively visualize thrombi, and may thus be a promising tool over alternative routine techniques for confirming the diagnosis of CVT.

Probable risk factors of internal jugular vein stenosis in Chinese patients-A real-world cohort study.

OBJECTIVES: Extracranial venous anomalies, especially internal jugular vein stenosis (IJVS), have recently received increasing attention, however, its etiologies are uncertain. This study aimed to explore the probable risk factors of IJVS in Chinese PATIENTS AND METHODS: Eligible patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. Probable risk factors were analyzed, including the conditions that may result in IJV wall damage, extraluminal compression, gender and age. RESULTS: A total of 133 patients enrolled in the final analysis, including 73 females and 60 males, the mean age were 54.83 ±â€¯15.25 years. In this IJVS cohort, the top two risks were previous hepatitis B virus (HBV) infection (48.9 %) and osseous compression (41.4 %). The IJVS cohort was divided into two subsets: extraluminal compression and non-compression. In the former, osseous compression (80.9 %) was the top risk factor, other risks including arterial (22.1 %) and lymph node compression (2.9 %). While, in the latter subset, the most common risk factor was previous HBV infection (46.2 %). In addition, cerebral venous sinus thrombosis (CVST) in non-compression subset was more common than that in extraluminal compression subset (21.5 % VS. 2.9 %, p = 0.001). When considered the gender (Male vs. Female), the ratios were 28.3 % vs. 0 % of smoking, p < 0.001, 16.67 % vs. 1.37 % of hyperhomocysteinemia, p = 0.002, and 11.67 % vs. 1.37 % of hyperuricemia, p = 0.023. In the subset with age less than 45 years, the top three risks included CVST (56.25 %), immunological diseases (55.56 %), and hyperhomocysteinemia (50.00 %), while, in the subset with the ages over 60 years, type-2 diabetes (66.66 %), carotid artery compression (53.33 %), previous HBV infection (52.31 %), and osseous compression (49.09 %) were more common than others. CONCLUSION: This study illustrates the probable risks of IJVS may be diverse, in which osseous compression and previous HBV infection may be the top two probable risks of IJVS in Chinese. This is the biggest difference from previous reports based on Caucasian.

Probable factors affecting clinical outcomes of internal jugular vein stenosis.

BACKGROUND: Internal jugular vein stenosis (IJVS) has recently aroused increasing interests, whereas, the factors affecting its clinical outcomes are not clear. This study aims to explore the probable factors affected clinical prognosis by evaluating the IJVS with different etiologies and strategies. METHODS: Patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. One-year clinical outcomes of the IJVS cases enrolled in this study were assessed by outpatient and telephone follow-up using the Patient Global Impression of Change (PGIC) scores. According to the etiologies, patients were divided into thrombotic IJVS and non-thrombotic IJVS groups. And further, non-thrombotic IJVS group was divided into external compression and non-external compression subgroups. Outcomes of IJVS with different etiologies and strategies were compared and the probable prognostic factors were analyzed. RESULTS: A total of 118 eligible patients enrolled in this study, including 76 females and 42 males, mean aged 55.07±14.61 years. The average follow-up duration after discharge was 13.22±3.80 months. According to the PGIC scores, we categorized patients as good outcome and poor outcome groups. For thrombotic IJVS, patients underwent standard anticoagulant obtained remarkable PGIC improvement (100.0% vs. 33.3%, P=0.038). For non-thrombotic IJVS, stenting showed benefit in non-external compression subgroup (26.9% vs. 3.3%, P=0.019) but not in external compression subgroup. In addition, we found that in this Chinese IJVS cohort, poor outcomes involved old age (P=0.004), type 2 diabetes mellitus (P=0.036), previous hepatitis B virus (HBV) infection (P=0.027), and head noises (P=0.002). Multivariate logistic regression analysis indicated that continuous head noises [P=0.045, odds ratio (OR): 2.412, 95% confidence interval (CI): 1.019-5.711], as a unique symptom of IJVS may be significantly related to poor outcomes. CONCLUSIONS: In this Chinese cohort, elderly degenerative bone compression, type 2 diabetes mellitus, and previous HBV infection are the top-three probable etiologies of non-thrombotic IJVS and may involve poor outcome. Long-term head noises may predict IJVS and with poor outcome. Thrombosis-induced IJVS may get benefit from standard anticoagulation. Non-external compression IJVS can be corrected by stenting.

[Evaluation on Ability to Detect the Intracranial Hematoma with Different Density Using C-Arm Cone-beam Computed Tomography Based on Animal Model].

This study aims to evaluate the ability of C-arm cone-beam CT to detect intracranial hematomas in canine models. Twenty one healthy canines were divided into seven groups and each group had three animals. Autologous blood and contrast agent (3 mL) were slowly injected into the left/right frontal lobes of each animal. Canines in the first group, the control group, were only injected with autologous blood without contrast agent. Each animal in all the 7 groups was scanned with C-arm cone-beam CT and multislice computed tomography (MSCT) after 5 minutes. The attenuation values and their standard deviations of the hematoma and uniformed brain tissues were measured to calculate the image noise, signal to noise ratio (SNR) and contrast to noise ratio (CNR). A scale with scores 1-3 was used to rate the quality of the reconstructed image of different hematoma as a subjective evaluation, and all the experimental data were processed with statistical treatment. The results revealed that when the density of hematoma was less than 65 HU, hematomata were not very clear on C-arm CT images, and when the density of hematoma was more than 65 HU, hematomata showed clearly on both C-arm CT and MSCT images and the scores of them were close. The coherence between the two physicians was very reliable. The same results were obtained with C-arm cone-beam CT and MSCT grades in measuring SD value, SNR, and CNR. The reasonable choice of density detection range of intracranial hematoma with C-arm cone-beam CT could be effectively applied to monitoring the intracranial hemorrhage during interventional diagnosis and treatment.

Application of low injection rate and low contrast agent dose in three-dimensional rotational digital subtraction angiography of the intracranial aneurysm.

OBJECTIVE: The objective of this article is to explore the feasibility of low injection rate and low contrast agent dose in three-dimensional rotational digital subtraction angiography (3D DSA) of the intracranial aneurysm. MATERIALS AND METHODS: Fifty-one patients with suspected intracranial aneurysms were included. The catheter tip was kept within the internal carotid artery at the epistropheus level. Patients were divided into three groups randomly according to injection rate: group A (1.5 ml/s, n = 18), group B (2.0 ml/s, n = 18), and group C (3.0 ml/s, n = 15). The noise, signal-to-noise ratio (SNR), and carrier-to-noise ratio (CNR) of C2, C6, M1, and A1 segments were calculated. The continuous subtraction images and reconstructed images were evaluated by two technicians. RESULTS: No significant differences were found in noise between groups A and B, and groups A and C. Significant differences were found in the SNR and CNR of M1 and A1 segments between groups A and B, and groups B and C, but for C2 and C6 segments, they were not significant. Significant differences were found in the SNR and CNR of all segments between groups A and C. Significant differences were found in the contrast agent dose between all three groups. No significant differences were found in scores evaluated by two physicians between the three groups. CONCLUSION: The personalized injection protocol of low injection rate and low contrast agent dose in 3D DSA of the intracranial aneurysm is feasible. The application of this protocol can reduce the dose of iodine and obtain satisfactory images.