Anti-inflammatory response-based risk assessment in acute type A aortic dissection: A national multicenter cohort study.

Background: Early identification of patients at high risk of operative mortality is important for acute type A aortic dissection (TAAD). We aimed to investigate whether patients with distinct risk stratifications respond differently to anti-inflammatory pharmacotherapy. Methods: From 13 cardiovascular hospitals, 3110 surgically repaired TAAD patients were randomly divided into a training set (70%) and a test set (30%) to develop and validate a risk model to predict operative mortality using extreme gradient boosting. Performance was measured by the area under the receiver operating characteristic curve (AUC). Subgroup analyses were performed by risk stratifications (low versus middle-high risk) and anti-inflammatory pharmacotherapy (absence versus presence of ulinastatin use). Results: A simplified risk model was developed for predicting operative mortality, consisting of the top ten features of importance: platelet-leukocyte ratio, D-dimer, activated partial thromboplastin time, urea nitrogen, glucose, lactate, base excess, hemoglobin, albumin, and creatine kinase-MB, which displayed a superior discrimination ability (AUC: 0.943, 95 % CI 0.928-0.958 and 0.884, 95 % CI 0.836-0.932) in the derivation and validation cohorts, respectively. Ulinastatin use was not associated with decreased risk of operative mortality among each risk stratification, however, ulinastatin use was associated with a shorter mechanical ventilation duration among patients with middle-high risk (defined as risk probability >5.0 %) (ß -1.6 h, 95 % CI [-3.1, -0.1] hours; P = 0.048). Conclusion: This risk model reflecting inflammatory, coagulation, and metabolic pathways achieved acceptable predictive performances of operative mortality following TAAD surgery, which will contribute to individualized anti-inflammatory pharmacotherapy.

Case report of epileptic seizure during awake craniotomy of functional area glioma and literature study.

Intraoperative seizure is the most prevalent and serious complication of awake craniotomy in functional areas, which may not only trigger complications of the surgical procedure or even the failure of awake craniotomy but also may result in adverse consequences to patients. The influencing factors of intraoperative seizures are unclear, and only the possible influencing factors can be acquired from the examination and summary of existing cases to offer guidance for the seizure prevention of intraoperative epilepsy.

Inflammatory profiles define phenotypes with clinical relevance in acute type A aortic dissection.

Association of distinct inflammatory profiles with short-term mortality is little known in type A aortic dissection (TAAD). Latent class analysis was used to identify distinct inflammatory profiles based on leukocyte, neutrophils, monocyte, lymphocytes, platelet, fibrinogen, D-dimer, neutrophils-lymphocyte ratio, platelet-lymphocyte ratio, and lymphocyte-monocyte ratio. We identified 193 patients with median age of 56 (IQR 47-63) years and 146 males. Patients were divided as hyper-inflammatory profiles (84 [43.5%]) and hypo-inflammatory profiles (109 [56.5%]). Although baseline characteristics were not different, hyper-inflammatory patients had higher 6-month mortality (20 [23.8%] vs. 11 [10.1%]; P = 0.014) and 30-day mortality (18 [21.4%] vs. 9 [8.3%], P = 0.009) than hypo-inflammatory patients. After adjustment for potential confounders, hyper-inflammatory profiles remain associated with higher risk of 6-month mortality than hypo-inflammatory profiles (adjusted OR 2.427 [95%CI 1.154, 5.105], P = 0.019). Assessment of preoperative inflammatory profiles adds clarity regarding the extent of inflammatory response to TAAD aetiopathologies, highlighting individual anti-inflammatory pharmacotherapy for TAAD. ClinicalTrials.gov Identifier: NCT04398992.

Prognostic Implication of Pulmonary Arterial Pressure in Surgical Repair of Predominantly Congenital Mitral Valve Regurgitation-Based Intracardiac Abnormalities.

INTRODUCTION: Knowledge is limited regarding the significance of pulmonary arterial pressure (PAP) in predominantly congenital mitral valve regurgitation (MR)-based intracardiac abnormalities. METHODS: From a prospective cohort, we included 200 patients with congenital MR regardless of other associated intracardiac abnormalities (mean age 60.4 months, 67% female, systolic PAP (sPAP) 54.2 mm Hg) surgically repaired in 2012-2019 and followed up to 2020 (median 30.0 months). Significant pulmonary hypertension (PH) was defined as sPAP >50 mm Hg at rest or mean PAP >25 mm Hg on right heart catheterization. By perioperative sPAP changes, patients were stratified as group I (pre-normotension to post-normotension), group II (pre-hypertension to post-normotension), or group III (pre-hypertension to post-hypertension). Primary outcomes were the recurrence of MR (defined as the regurgitation grade of moderate or greater) and the progression of MR (defined as any increase in the magnitude of regurgitation grade after surgery). Cox proportional hazard and Kaplan-Meier curve were performed. RESULTS: There was no association between preoperative PH and the recurrent MR (adjusted hazard ratios [aHR]: 1.146 [95% CI: 0.453-2.899]) and progressive MR (aHR: 1.753 [95% CI: 0.807-3.804]), respectively. There were no significant differences among group I, group II, and group III in the recurrent MR but in the progressive MR. A dose dependency was identified for preoperative sPAP with recurrent MR (aHR: 1.050 [95% CI: 1.029-1.071]) and progressive MR risks (aHR: 1.037 [95% CI: 1.019-1.055]), respectively. CONCLUSIONS: Preoperative higher sPAP is associated with worse outcomes, warranting heightened attention to the identification of perioperative sPAP.

Circulating biomarker-based risk stratifications individualize arch repair strategy of acute Type A aortic dissection via the XGBoosting algorithm.

Aims: The incremental usefulness of circulating biomarkers from different pathological pathways for predicting mortality has not been evaluated in acute Type A aortic dissection (ATAAD) patients. We aim to develop a risk prediction model and investigate the impact of arch repair strategy on mortality based on distinct risk stratifications. Methods and results: A total of 3771 ATAAD patients who underwent aortic surgery retrospectively included were randomly divided into training and testing cohorts at a ratio of 7:3 for the development and validation of the risk model based on multiple circulating biomarkers and conventional clinical factors. Extreme gradient boosting was used to generate the risk models. Subgroup analyses were performed by risk stratifications (low vs. middle-high risk) and arch repair strategies (proximal vs. extensive arch repair). Addition of multiple biomarkers to a model with conventional factors fitted an ABC risk model consisting of platelet-leucocyte ratio, mean arterial pressure, albumin, age, creatinine, creatine kinase-MB, haemoglobin, lactate, left ventricular end-diastolic dimension, urea nitrogen, and aspartate aminotransferase, with adequate discrimination ability {area under the receiver operating characteristic curve (AUROC): 0.930 [95% confidence interval (CI) 0.906-0.954] and 0.954, 95% CI (0.930-0.977) in the derivation and validation cohort, respectively}. Compared with proximal arch repair, the extensive repair was associated with similar mortality risk among patients at low risk [odds ratio (OR) 1.838, 95% CI (0.559-6.038); P = 0.316], but associated with higher mortality risk among patients at middle-high risk [OR 2.007, 95% CI (1.460-2.757); P < 0.0001]. Conclusion: In ATAAD patients, the simultaneous addition of circulating biomarkers of inflammatory, cardiac, hepatic, renal, and metabolic abnormalities substantially improved risk stratification and individualized arch repair strategy.

Transplantation of Nurr1-overexpressing neural stem cells and microglia for treating parkinsonian rats.

BACKGROUND: Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment. METHODS: In this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr1 gene were transplanted into the striatum of the rat model of PD. The results were evaluated through reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence analysis. RESULTS: The behavioral abnormalities of PD rats were improved by combined transplantation of NSCs and microglia, both forced with Nurr1. The number of tyrosine hydroxylase+ cells in the striatum of PD rats increased, and the number of Iba1+ cells decreased compared with the other groups. Moreover, the dopamine neurons differentiated from grafted NSCs could still be detected in the striatum of PD rats after 5 months. CONCLUSIONS: The results suggested that transplantation of Nurr1-overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be  a new potential strategy for the cell replacement therapy in PD.

Nurr1 promotes neurogenesis of dopaminergic neuron and represses inflammatory factors in the transwell coculture system of neural stem cells and microglia.

INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life. AIM: This study investigated the effect of Nurr1 on neuroinflammation and differentiation of NSCs cocultured with primary microglia in the transwell coculture system. RESULTS: The results showed that Nurr1 exerted anti-inflammatory effects and promoted the differentiation of NSCs into dopaminergic neurons. CONCLUSIONS: The results suggested that Nurr1 protects dopaminergic neurons from neuroinflammation insults by limiting the production of neurotoxic mediators by microglia and maintain the survival of transplanted NSCs. These phenomena provided a new theoretical and experimental foundation for the transplantation of Nurr1-overexpressed NSCs as a potential treatment of PD.

Association between previously identified loci affecting telomere length and coronary heart disease (CHD) in Han Chinese population.

PURPOSE: To replicate previously confirmed telomere-length loci in a Chinese Han population with coronary heart disease (CHD), and investigate these loci and the possibility of and age at onset of CHD. PATIENTS AND METHODS: 1514 CHD patients and 2470 normal controls were recruited. Medical data including age, sex, body mass index, lipid profiles, history of hypertension, type 2 diabetes mellitus, and dyslipidemia were collected from all the participants. Seven previously identified single-nucleotide polymorphisms (SNPs) related to leucocyte telomere length were genotyped, including rs10936599 in TERC, rs2736100 in TERT, rs7675998 in NAF1, rs9420907 in OBFC1, rs8105767 in ZNF208, rs755017 in RTEL1, and rs11125529 in ACYP2. RESULTS: No significant difference in genotype frequencies from the Hardy-Weinberg equilibrium test was noted for all tested SNPs both in the CHD patients and the normal controls. No polymorphism was observed for rs9420907, and AA genotype was noted in both the CHD patients and the controls. Neither the genotype nor the allele frequencies of rs2736100, rs8105767, rs11125529, and rs2967374 were significantly different between the CHD patients and the normal controls. For rs10936599 and rs755017, statistical difference was found for the allele frequency but not genotype. Distributions of genotype and allele were significantly different between the two groups for rs7675998. The odds ratio for carriers of CHD was 2.127 (95% confidence interval: 1.909-2.370) for the A allele of rs7675998. By one-way analysis of variance test, rs7675998 was associated with the onset age of CHD. CHD patients with the AA genotype of rs7675998 had significantly lower onset age (P<0.05). CONCLUSION: In a Chinese Han population, NAF1 gene encoding proteins with known function in telomere biology may influence both the possibility of and the age at onset of CHD, as previously reported in European studies.

[The correlation between Chlamydiae pneumonia and carotid atherosclerosis].

OBJECTIVES: To study the correlation between Chlamydiae pneumonia and carotid atherosclerosis, and the correlation between the infection of Chlamydiae pneumonia and ischemic events. METHODS: The study group consisted of 19 patients who underwent unilateral carotid endarterectomy surgery during the period from January 2010 to December 2011, and the atherosclerotic plaque specimens were harvested from these patients. The control group consisted of 10 patients who underwent extracranial-intracranial bypass surgery during the same period, and the normal external carotid artery specimens were got from these patients. The clinical data between the two groups had comparability. The presence of Chlamydiae pneumonia in atherosclerotic plaque and normal artery tissue were investigated by immunohistochemistry. The expression of Toll-like receptor 2 (TLR2), tumor necrosis factor-α (TNF-α) and vascular cell adhesion molecule-1 (VCAM-1) in the atherosclerotic plaque infected with Chlamydiae pneumonia were also detected. Data were analyzed using Fisher's exact test. RESULT: Chlamydiae pneumonia was found in 9 of 19 atherosclerotic plaques, while no positive result was found in control group. The statistical analysis showed a significant difference (P = 0.011). Among the 19 patients in study group, 15 of them had ischemic events, and Chlamydiae pneumonia was found in 9 of these 15 patients; while the other 4 patients didn't have any ischemic events and no Chlamydiae pneumonia was found in them, but there was no statistical different between them (P = 0.087). Through immunohistochemistry, the expression of Chlamydiae pneumonia, TLR2, TNF-α and VCAM-1 were found in same area. CONCLUSIONS: There is a correlation between Chlamydiae pneumonia and carotid atherosclerosis.And there might be a correlation between Chlamydiae pneumonia and cerebral ischemic events.

Effects of congenital cataract mutation R116H on alphaA-crystallin structure, function and stability.

alpha-crystallin is a molecular chaperone that maintains the optical properties of the lens and delays the onset scattering caused by aging-related protein aggregation. In this research, we found that the missense mutation R116H resulted in an altered size distribution, impaired packing of the secondary structures and modified quaternary structure with great hydrophobic exposure. The mutant exhibited a substrate-dependent chaperone (aggregation-inhibition) or anti-chaperone (aggregation-promotion) effect. Equilibrium unfolding experiments indicated that the mutation stabilized an aggregation-prone intermediate which was not populated during the unfolding of the wild-type protein. The accumulation of this intermediate greatly promoted the formation of non-native large oligomers or aggregates during unfolding. These results suggested that both the aggregation of the mutant upon stress and co-deposition with the target proteins were likely to be responsible for the onset of cataract.

[Surgical treatment of vertebral artery-posterior inferior cerebellar artery dissecting aneurysms].

OBJECTIVE: To study an effective method for vertebral artery-posterior inferior cerebellar artery (VA-PICA) dissecting aneurysms. METHODS: Five patients with VA-PICA dissecting aneurysms were treated surgically between December 2007 and February 2010, who were all males, aged from 40 to 55 years. Four of them presented with subarachnoid hemorrhage (SAH), 1 of them suffered from an intermittent headache on occipital area about 4 months. All the aneurysms were trapped via a far-lateral approach after revascularization of the PICAs by occipital artery-posterior inferior cerebellar artery (OA-PICA) bypass. RESULTS: Among the 5 patients, 1 of them got a good outcome without any neurological deficit after surgery, 3 of them had postoperative lower cranial nerve palsy, 1 of them complicated with bleeding in the operative field after postoperative antithrombotic treatment, and suffered from contralateral hemiplegia after second surgery of removing hematoma. Postoperative cerebral angiographies (received by 2 patients) and CT angiographies (received by 3 patients) all showed patent bypasses and no filling of the aneurysms. During the follow-up from 2 to 29 months, 4 patients got good outcomes, 1 patient still suffered from moderate hemiplegia. CONCLUSIONS: Trapping the aneurysms after revascularization of PICA by OA-PICA bypass should be an effective method to treat the VA-PICA dissecting aneurysms, but individualized strategies also need to be considered based on different cases.

Poly[[tetraaqua-bis(µ(3)-1H-benzimidazole-5,6-dicarboxyl-ato)dicobalt(II)] trihydrate].

The title complex, {[Co(2)(C(9)H(4)N(2)O(4))(2)(H(2)O)(4)]·3H(2)O}(n), was synthesized hydro-thermally. The unique Co(II) ion is coordin-ated in a distorted octa-hedral coordination environment by two water mol-ecules and three symmetry-related 1H-benzimid-azole-5,6-dicarboxyl-ate (Hbidc) ligands. The Hbidc ligands coordinate via a bis-chelating and mono-chelating carboxyl-ate group and by an imidazole group N atom, bridging the Co(II) ions and forming an extended two-dimensional structure in the ab plane. In the crystal structure, inter-molecular N-H⋯O and O-H⋯O hydrogen bonds connect complex and solvent water mol-ecules, forming a three-dimensional supermolecular network. One of the solvent water mol-ecules lies on a twofold rotation axis.

catena-Poly[[[tetra-aqua-manganese(II)]-µ-4,4'-bipyridine] bis-(3-hydroxy-cinnamate) dihydrate].

The title compound, {[Mn(C(10)H(8)N(2))(H(2)O)(4)](C(9)H(7)O(3))(2)·2H(2)O}(n), was obtained by the hydro-thermal reaction of manganese chloride with mixed 3-hydroxy-lcinnamic acid (H(2)L) and 4,4'-bipyridine (4,4'-bipy) ligands. The structure contains [Mn(C(10)H(8)N(2))(H(2)O)(4)](2+) cations with the Mn(II) atoms lying on a centres of inversion and bridged into a linear chain along the a axis by 4,4'-bipy ligands, surrounded by HL(-) anions and uncoordinated water mol-ecules. Extensive O-H⋯O hydrogen-bonding and weak π-π inter-actions [centroid-centroid distance = 3.7572  (3) Å] between the constituents lead to the formation of a three-dimensional supra-molecular network.

Expression of a telomerase-associated gene in normal, atrophic, and tumorous testes.

OBJECTIVE: To evaluate the expression of telomerase transcriptional elements-interacting factor (TEIF) in human testis under different status and its relation with human telomerase reverse transcriptase (hTERT) expression. METHODS: Specific antisera against TEIF were generated by immunization of rabbits with purified recombinated partial TEIF. Samples were assigned to three groups according to their pathological types, including 16 normal testes, 8 atrophic testes, and 6 testicular seminomas. They were subjected to immunohistochemical staining of TEIF and hTERT. Results from both TEIF and hTERT were analyzed semi-quantitatively and compared. RESULTS: The expressions of TEIF and hTERT were detected in all samples of normal, atrophic testes, and seminomas. No differences of TEIF expressions among these three groups were observed (P > 0.05). On the contrary, the expressions of hTERT were significantly lower in atrophic testes compared with those of normal testes and seminomas (both P < 0.05). Nevertheless, co-expressions of TEIF with hTERT were revealed to be in normal and malignant cases (P < 0.05) but not in atrophic testes, which generally presented TEIF expression. The cellular distributions of both proteins were similar and mainly in spermatocytes and some Sertoli cells, while were all negative in the interstitial cells and other stromal cells. Conclusions The uniform expressions of TEIF in all these specimens suggest that it may be a marker of testis and its related diseases. The strong expression of hTERT in normal testes and testicular seminomas comparing with the low expression in atrophic testes may suggest a role for telomerase in maintaining proliferation of germ cells.