[Predictive value of whole brain perfusion on admission for shunt-dependent hydrocephalus fllowing aneurysmal subarachnoid hemorrhage].

Objective: To explore the value of predicting shunt-dependent hydrocephalus (SDHC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) based on whole brain CT perfusion(CTP) and clinical data within 24 hours at admission. Methods: The clinical and imaging data of aSAH patients who received interventional embolization in our hospital were retrospectively collected from March 2018 to August 2022. All patients underwent one-stop whole brain CT examination within 24 hours after symptom onset, and the qualitative and quantitative CTP parameters were obtained after post-processing. Follow-up was conducted once every 2 months by consulting electronic medical records or by telephone for 6 months. According to whether SDHC occurred or not, the patients were divided into SDHC group and non-SDHC group. The differences between the two groups were compared. Logistic regression model was used to analyze and determine the predictive factors of SDHC, and the SDHC predictive model was established. The effectiveness of the predictive model was evaluated by drawing the receiver operating characteristic (ROC) curve of the subjects. Results: A total of 414 patients were included, including 132 males and 282 females, aged (59±11) years. 17.6%(73/414) patients had SDHC. There were significant differences in the occurrence of acute hydrocephalus, the World Neurosurgical League Scale (WFNS), the Hunt-Hess scale, the modified Fisher score (mFS), and the qualitative and quantitative parameters of CTP between the two groups (both P<0.001). Multivariate logistic regression analysis showed that acute hydrocephalus (OR=8.621, 95%CI: 4.237-17.542),old age (OR=1.107, 95%CI: 1.068-1.148), high mFS and high Hunt-Hess classification (OR=3.740, 95%CI: 1.352-10.342) were the risk factors of SDHC in aSAH patients, and high mean cerebral blood flow (mCBF) (OR=0.931, 95%CI: 0.885-0.980) was a protective factor of SDHC.The area under ROC curve (AUC) of the prediction model constructed by these five variables was 0.923(95%CI: 0.89-0.95), with 84.5% sensitivity and 87.7% specificity. Conclusion: The mCBF and acute hydrocephalus, age, mFS and Hunt-Hess classification within 24 hours at admission can be used to predict SDHC for aSAH patients.

Association of cord plasma metabolites with birth weight: results from metabolomic and lipidomic studies of discovery and validation cohorts.

BACKGROUND: Birth weight is a good predictor of fetal intrauterine growth and long-term health. Although several studies have evaluated the relationship between metabolites and birth weight, no prior study has comprehensively investigated the metabolomic and lipidomic and further validated and quantified meaningful metabolites. METHODS: Firstly, a pseudotargeted metabolomics approach was applied to detect 2418 metabolites in 504 cord blood samples in the discovery set enrolled from the Wuhan Healthy Baby Cohort (HBC), China. Metabolome-wide association scan (MWAS) analysis and pathway enrichment were applied to discover metabolites and metabolic pathways that were significantly associated with birth weight for gestational age (BWGA) z-score. Logistic regression models were used to analyze the association of metabolites in the most significantly associated pathways with small for gestational age (SGA) and low birth weight (LBW). Subsequently, 350 cord blood samples in a validation cohort were subjected to targeted analysis to validate the metabolites screened from the discovery cohort. RESULTS: In the discovery set, 513 metabolites were significantly associated with BWGA z-score (PFDR <0.05), of which 298 KEGG-annotated metabolites were included in the pathway analysis. The primary bile acid biosynthesis pathway was the most relevant metabolic pathway associated with BWGA z-score in our study. Elevated cord plasma primary bile acids were associated with lower BWGA z-score and higher odds of SGA or LBW in the discovery and validation cohorts. In the validation set, a 2-fold increase in taurochenodeoxycholic acid (TCDCA) and taurocholic acid (TCA) was associated with 0.10 (95% CI: 0.00, 0.20) and 0.18 (95 %CI: 0.04, 0.31) decrease in BWGA z-score, respectively, after adjusting for covariates. In addition, a 2-fold increase in cord plasma TCDCA and TCA was associated with an adjusted odds ratio of 1.52 (1.00, 2.30) and 1.77 (1.05, 2.98) for SGA, respectively. The adjusted ORs for a 2-fold increase in TCDCA and TCA concentrations were 2.39 (95% CI 1.00, 5.71) and 3.21 (0.96, 10.74) for LBW, respectively. CONCLUSIONS: The results indicate a significant association between primary bile acids and lower BWGA z-score, as well as higher risk of SGA and LBW. Abnormalities of primary bile acid metabolism may play an important role in restricted fetal development. This article is protected by copyright. All rights reserved.

18F-FDG PET/CT-based radiomics model for predicting the degree of pathological differentiation in non-small cell lung cancer: a multicentre study.

AIM: To explore the value of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)-based radiomics model for predicting the degree of pathological differentiation in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Clinical characteristics of 182 NSCLC patients from four centres were collected, and radiomics features were extracted from 18F-FDG PET/CT images. Three logistic regression prediction models were established: clinical model; radiomics model; and nomogram combining radiomics signatures and clinical features. The predictive ability of the models was assessed using receiver operating characteristics curve analysis. RESULTS: Patients from centre 1 were assigned randomly to the training and internal validation cohorts (7:3 ratio); patients from centres 2-4 served as the external validation cohort. The area under the curve (AUC) values for the clinical model in the training, internal validation, and external validation cohort were 0.74 (95% confidence interval [CI] = 0.64-0.84), 0.64 (95% CI = 0.46-0.81), and 0.74 (95% CI = 0.60-0.88), respectively. In the training (AUC: 0.84 [95% CI = 0.77-0.92]), internal validation (AUC: 0.81 [95% CI = 0.67-0.95]), and external validation cohorts (AUC: 0.74 [95% CI = 0.58-0.89]), the radiomics model showed good predictive ability for differentiation. Compared to the clinical and radiomics models, the nomogram has relatively better diagnostic performance, and the AUC values for nomogram in the training, internal validation, and external validation cohort were 0.86 (95% CI = 0.78-0.93), 0.83 (95% CI = 0.70-0.96), and 0.77 (95% CI = 0.62-0.92), respectively. CONCLUSIONS: The 18F-FDG PET/CT-based radiomics model showed good ability for predicting the degree of differentiation of NSCLC. The nomogram combining the radiomics signature and clinical features has relatively better diagnostic performance.

The jigsaw puzzle of pedigree: whole-genome resequencing reveals genetic diversity and ancestral lineage in Sunong black pigs.

The Sunong black pig is a new composite breed under development generated from Chinese indigenous pig breeds (i.e., Taihu and Huai) and intensive pig breeds (i.e., Landrace and Berkshire), which is an important genetic material for studying breeding mechanisms. However, there is currently limited knowledge about the genetic structure and germplasm characteristics of Sunong black pigs. To comprehensively understand their genetic composition and ancestry proportions, we performed population structure and local ancestry inference analysis based on whole-genome sequencing information. The results showed that Sunong black pigs could be clustered independently into a group, whose pedigree was intermediate between indigenous and commercial pig breeds, but closer to commercial pigs. Furthermore, local ancestry inference analysis revealed that Sunong black pigs inherited immune and reproductive traits from indigenous pig breeds, including CC and CXC chemokine family, Toll-like receptor family, IFN gene family, ESR1, AREG and EREG gene, while growth and development-related traits were inherited from commercial pig breeds, including IGF1 and GSY2 gene. Overall, Sunong black pigs have formed a relatively stable genome structure with some advantageous traits inherited from their ancestral breeds. This study deepened the understanding of the breeding mechanism of Sunong black pigs and provided a reference for cross-breeding programmes in livestock.

[Topography-guided transepithelial corneal collagen cross-linking by sequential ultraviolet A irradiation in different diameters for progressive keratoconus in adults].

Objective: To compare the efficacy and safety of a novel customized topography-guided transepithelial corneal collagen cross-linking (TG-CXL) procedure by sequential ultraviolet A irradiation in different diameters and conventional transepithelial corneal collagen cross-linking (TE-CXL) in adult patients with progressive keratoconus. Methods: A prospective cohort study was conducted. Adult patients diagnosed with progressive keratoconus in the Affiliated Xiamen Eye Center of Xiamen University were continuously recruited and randomly assigned to receive the TG-CXL or TE-CXL procedure from March 2020 to March 2021. Patients in the TE-CXL group were irradiated in the central 9-mm zone of the cornea (total energy, 7.2 J/cm2; irradiance, 45 mW/cm2), while patients in the TG-CXL group were first irradiated with the protocol used in the TE-CXL group, and further irradiated in the central 6-mm zone (total energy, 3.6 J/cm2; irradiance, 9 mW/cm2). The subjective symptom of pain and corneal fluorescein sodium staining were scored within postoperative 3 days. Slit lamp examination, measurements of uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), corneal topography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy, corneal endothelial cell count, and non-contact tonometry were performed before surgery and at 3, 6, and 12 months after surgery. Results: A total of 66 patients were enrolled (mean age, 23.0±3.3 years old), with 33 patients (33 eyes) in each group. No statistically significant differences were found in age, gender, and maximum keratometry (Kmax) between the two groups (P>0.05). On day 1 after surgery, the average pain score of the TG-CXL group (2.21±0.45) was significantly higher than that of the TE-CXL group (1.32±0.33) (P<0.05). The pain was rapidly alleviated in both groups on days 2 and 3. On days 1 and 2, the corneal fluorescein sodium staining scores in the TG-CXL group (4.15±0.83 and 2.21±0.60, respectively) were significantly higher than those in the TE-CXL group (1.76±0.56 and 0.85±0.51, respectively, P<0.001), while there was no significant difference between the two groups at day3 (P=0.184). The UCVA and BCVA of the TG-CXL group at 3, 6, and 12 months after surgery were significantly improved when compared with the baseline. At 3, 6, and 12 months, the BCVA (LogMAR) of the TG-CXL group (0.21±0.15, 0.22±0.16, and 0.22±0.16, respectively) were significantly improved when compared with those of the TE-CXL group(0.32±0.15, 0.34±0.15, and 0.36±0.16, respectively, P<0.01). However, there was no significant difference in UCVA between groups at any time point after surgery (P>0.05). The spherical and cylindrical power values of the TG-CXL group were improved when compared with the baseline (P<0.05). However, no significant difference in spherical power values was found between the two groups at any time point after surgery (P>0.05). Meanwhile, there were significant differences in cylindrical power values between the two groups at 6 and 12 months after surgery (P<0.05). The Kmax in the TG-CXL group was improved at all of the time points after surgery when compared with the baseline (P<0.001), while no significant difference in Kmax was found at any time point after surgery in the TE-CXL group when compared with the baseline (P>0.05). At 6 and 12 months after surgery, the Kmax values in the TG-CXL group were significantly lower than the TE-CXL group (P<0.05). No significant differences were found in flat keratomety, steep keratometry, the minimal thickness of the cornea, endothelial cell density, and intraocular pressure between the two groups at any time point after surgery (P>0.05). Within one month after surgery, optical coherence tomography revealed the increased density in the anterior stroma in both groups. In most patients in the TG-CXL group, a demarcation line was visible in the central and para-central corneal stroma, representing a clear and continuous, high-signal arc-shaped linear structure, which was deeper in the central cornea than the para-central cornea. In contrast, a demarcation line, fuzzy and focally discontinuous, was visible only in a few patients in the TE-CXL group, with an almost uniform depth in the central and the para-central cornea. Confocal microscopy demonstrated an apparent mesh-like cross-linked collagen structure in the superficial and intermediate corneal stroma at all time points after surgery in the TG-CXL group, with thickening stromal collagen fibers and an increased number of interconnections. In contrast, the mesh-like structure and number of interconnections in the superficial corneal stroma were significantly reduced at 12 months after surgery in the TE-CXL group, with no cross-linking structure in the intermediate corneal stroma at any time point after surgery. No serious complications such as corneal infection, sterile corneal ulcer, and persistent epithelial defect were observed in both groups during the follow-up of 12 months. Conclusions: The TG-CXL procedure by sequential irradiation in two different diameters with ultraviolet A light was effective and safe in the management of progressive keratoconus in adults, achieving significant refractive improvement. This might be a good technical alternative for refractive corneal cross-linking surgery.

[Exploration of making removable partial denture by digital technology].

To explore the digital manufacturing process of distal extension removable partial denture. From November 2021 to December 2022, 12 patients (7 males and 5 females) with free-ending situation were selected from the Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University. Three-dimensional model of the relationship between alveolar ridge and jaw position was obtained by intraoral scanning technique. After routine design, manufacturing and try-in of metal framework for removable partial denture, the metal framework was located in the mouth and scanned again to obtain the composite model of dentition, alveolar ridge and metal framework. The free-end modified model is obtained by merging the digital model of free-end alveolar ridge with the virtual model with the metal framework. The three-dimensional model of artificial dentition, and base plate was designed on the free-end modified model, and the resin model were made by digital milling technology. The removable partial denture was made by accurately positioning the artificial dentition and base plate, bonding metal framework with injection resin, grinding and polishing the artificial dentition and resin base. Compared with the design data after clinical trial, the results showed that there was an error of 0.4-1.0 mm and an error of 0.03-0.10 mm in the connection between the resin base of artificial dentition and the connecting rod of the in-place bolt and the connection between artificial dentition and resin base. After denturen delivery, only 2 patients needed grinding adjustment in follow-up visit due to tenderness, and the rest patients did not find any discomfort. The digital fabrication process of removable partial denture used in this study can basically solve the problems of digital fabrication of free-end modified model and assembly of artificial dentition with resin base and metal framework.

Nomogram for evaluating coronary revascularisation necessity based on multi-parameter coronary CT angiography.

AIM: To build a nomogram model to improve the evaluation of revascularisation necessity using multi-parameter coronary computed tomography (CT) angiography (CCTA). MATERIALS AND METHODS: In this retrospective study, 335 patients who underwent CCTA and required revascularisation within 1 month were selected and allocated to the revascularisation group; 208 patients who did not undergo revascularisation were allocated to the non-revascularisation group. CCTA parameters, including CCTA stenosis, plaque qualitative-quantitative characteristics, and fractional flow reserve derived from CT angiography (CT-FFR), for both groups were analysed and compared. Independent risk factors for evaluating revascularisation were obtained using univariate and multivariable regression analysis, after which multi-parameter models were built. Finally, a nomogram was created with these independent risk factors using the R programming language. RESULTS: Plaque analysis was performed successfully for 543 patients with 1,072 target plaques. The performance of the multi-parameter model (AUC 0.894, p<0.001) was significantly higher than that of models based on stenosis (AUC 0.804, p<0.001), plaque qualitative/quantitative characteristics (AUC 0.754/0.789, p<0.001), or CT-FFR (AUC 0.848, p<0.001) alone, to evaluate the necessity of revascularisation. The independent risk factors were CCTA stenosis (OR 1.004, p=0.04), positive remodelling (OR 2.474, p<0.001), total plaque volume (OR 1.001, p<0.001), non-calcified plaque volume proportion (OR 1.019, p<0.001), and CT-FFR (OR 0.001, p<0.001). Subsequently, a nomogram based on these factors was created. CONCLUSION: The multi-parameter CCTA model improved performance in evaluating revascularisation necessity. The nomogram based on these factors is shows promise in clinical settings.

[Short-term efficacy of dapagliflozin in children with hereditary proteinuric kidney disease].

Objective: To explore the short-term efficacy and safety of dapagliflozin in children with hereditary proteinuric kidney disease. Methods: This was a prospective cohort study. From August 2020 to December 2021, 23 children with hereditary kidney disease from Children's Hospital of Fudan University were enrolled. Patients received dapagliflozin 5 mg/d (weight≤30 kg) or initial dose 5 mg/d for 1 week, then 10 mg/d (weight>30 kg) and the dose of angiotensin converting enzyme inhibitors was stable during treatment. Clinical data including demographic parameters, primary diagnosis, estimated glomerular filtration rate (eGFR), 24 h proteinuria and characteristics in the follow-up were collected. The primary outcome was the change in 24 h proteinuria at 12 (±2) weeks, secondary outcomes included changes of 24 h proteinuria at 24 (±2) weeks, eGFR at both 12 (±2) and 24 (±2) weeks. The data were analysed by using mixed linear model. Results: Totally 23 patients were enrolled, including 16 males and 7 females. The age was (10.8±2.9) years. The primary diseases were Alport syndrome (12 cases), Dent disease (5 cases), proteinuria (4 cases), and focal segmental glomerulosclerosis (2 cases) respectively. Primary outcome showed that 24 h proteinuria decreased from baseline at 12 (±2) weeks during treatment (1.75 (1.46, 2.20) vs. 1.84 (1.14, 2.54) g/m2, P<0.05). Secondary outcomes showed that there was no significant difference in 24 h urine protein at 24 (±2) weeks (P>0.05). eGFR decreased slightly at 12 (±2) weeks ((107±21) vs. (112±28) ml/(min·1.73m2), P<0.05), and there was no significant difference at 24 (±2) weeks (P>0.05). Serum albumin increased at 12 (±2) and 24 (±2) weeks following the treatment ((39±8) vs. (37±8) g/L, (38±7) vs. (37±8) g/L, both P<0.05). No hypoglycemia event was reported during the treatment. Conclusion: The dapagliflozin had therapeutic effects on decreasing proteinuria and increasing serum albumin in short-term treatment in children with hereditary proteinuric kidney disease, no hypoglycemia or serious adverse events were observed.

[A multicenter, double-blind, randomized controlled clinical trial comparing ergometrine with oxytocin and oxytocin alone for prevention of postpartum hemorrhage at cesarean section].

Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant (P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups (P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant (P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

[Role of the CCL28-CCR10 pathway in monocyte migration in rheumatoid arthritis].

OBJECTIVE: To examine the expression of chemokine receptor CCR10 on monocytes/macrophages in the joints of patients with rheumatoid arthritis (RA), and to investigate the role of chemokine CCL28 and its receptor CCR10 in the migration of RA monocytes and its mechanism. METHODS: The expression of CCR10 in synovial tissues from 8 RA patients, 4 osteoarthritis (OA) patients, and 4 normal controls was analyzed by immunohistochemistry, and cell staining was scored on a 0-5 scales. Flow cytometry was used to measure the percentage of CCR10 positive cells in CD14+ monocytes from peripheral blood of 26 RA patients and 20 healthy controls, as well as from synovial fluid of 15 RA patients. The chemotactic migration of monocytes from RA patients and healthy controls in response to CCL28 was evaluated using an in vitro Transwell system. Western blotting was conducted to assess phosphorylation of the extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) pathways in RA monocytes upon CCL28 treatment. RESULTS: CCR10 was predominantly expressed in RA synovial lining cells and sublining macrophages, endothelial cells, and lymphocytes. CCR10 expression was significantly increased on lining cells and sublining macrophages in RA synovial tissue compared with OA and normal synovial tissue (both P < 0.01). The patients with RA had markedly elevated expression of CCR10 on peripheral blood CD14+ monocytes compared with the healthy controls [(15.6±3.0)% vs. (7.7±3.8)%, P < 0.01]. CCR10 expression on synovial fluid monocytes from the RA patients was (32.0±15.0)%, which was significantly higher than that on RA peripheral blood monocytes (P < 0.01). In vitro, CCL28 caused significant migration of CD14+ monocytes from peripheral blood of the RA patients and the healthy controls at concentrations ranging from 10-100 µg/L (all P < 0.01). The presence of neutralizing antibody to CCR10 greatly suppressed CCL28-driven chemotaxis of RA monocytes (P < 0.01). Stimulation of RA monocytes with CCL28 induced a remarkable increase in phosphorylation of ERK and Akt (both P < 0.05). ERK inhibitor (U0126) and phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) strongly reduced the migration of RA monocytes in response to CCL28 (both P < 0.01). CONCLUSION: RA patients had increased CCR10 expression on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages. CCL28 ligation to CCR10 promoted RA monocyte migration through activation of the ERK and PI3K/Akt signaling pathways. The CCL28-CCR10 pathway could participate in monocyte recruitment into RA joints, thereby contributing to synovial inflammation and bone destruction.

Deep Underground Laboratory Measurement of

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

Risk factors for hearing loss in neonates admitted to neonatal intensive care units.

OBJECTIVE: This study aimed to research risk factors of hearing loss among neonates in the neonatal intensive care unit. METHOD: Hearing screening tests were performed on 572 neonates in the neonatal intensive care unit. Those who failed screening tests were referred for diagnostic tests. RESULTS: The pass rates for automated auditory brainstem response, distortion product otoacoustic emission and acoustic impedance tests at first hearing screening were 69.93 per cent, 70.02 per cent and 92.92 per cent for 1144 ears. Failure in the first screening correlated with preterm birth, very low birth weight, revised advanced maternal age, neonatal hyperbilirubinaemia and Activity, Pulse, Grimace, Appearance, Respiration score less than 8. Thirty cases failed in diagnostic hearing tests for brainstem auditory evoked potentials, 28 failed in otoacoustic emissions and 33 failed in acoustic impedance, which correlated with preterm birth, very low birth weight, twins, advanced maternal age and revised advanced maternal age. CONCLUSION: Abnormalities in the hearing levels of most neonates who needed hearing retests were completely or partially reversible. Preterm birth, very low birth weight, twins and advanced maternal age are potential risk factors for hearing impairment.

[Naringenin inhibits thoracic aortic aneurysm formation in mice with Marfan syndrome].

OBJECTIVE: To identify whether naringenin plays a protective role during thoracic aneurysm formation in Marfan syndrome. METHODS: To validate the effect of naringenin, Fbn1C1039G/+ mice, the mouse model of Marfan syndrome, were fed with naringenin, and the disease progress was evaluated. The molecular mechanism of naringenin was further investigated via in vitro studies, such as bioluminescence resonance energy transfer (BRET), atomic force microscope and radioligand receptor binding assay. RESULTS: Six-week-old Fbn1C1039G/+ mice were fed with naringenin for 20 weeks. Compared with the control group, naringenin significantly suppressed the aortic expansion [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.49±0.47) mm, n=18 vs. (1.87±0.19) mm, n=22, P < 0.05], the degradation of elastin, and the expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the ascending aorta of Fbn1C1039G/+ mice. Besides, treatment with naringenin for 6 weeks also attenuated the disease progress among the 20-week-old Fbn1C1039G/+ mice with established thoracic aortic aneurysms [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.24±0.23) mm, n=8 vs. (1.90±0.17) mm, n=8, P < 0.05]. To understand the underlying molecular mechanisms, we examined the effects of naringenin on angiotensin Ⅱ type 1 receptor (AT1) signaling and transforming growth factor-ß (TGF-ß) signaling respectively, which were the dominant signaling pathways contributing to aortopathy in Marfan syndrome as previously reported. The results showed that naringenin decreased angiotensin Ⅱ (Ang Ⅱ)-induced phosphorylation of protein kinase C (PKC) and extracellular regulating kinase 1/2 (ERK1/2) in HEK293A cell overexpressing AT1 receptor. Moreover, naringenin inhibited Ang Ⅱ-induced calcium mobilization and uclear factor of activated T-cells (NFAT) signaling. The internalization of AT1 receptor and its binding to ß-arrestin-2 with Ang Ⅱ induction were also suppressed by naringenin. As evidenced by atomic force microscope and radioligand receptor binding assay, naringenin inhibited Ang Ⅱ binding to AT1 receptor. In terms of TGF-ß signaling, we found that feeding the mice with naringenin decreased the phosphorylation of Smad2 and ERK1/2 as well as the expression of TGF-ß downstream genes. Besides, the serum level of TGF-ß was also decreased by naringenin in the Fbn1C1039G/+ mice. Furthermore, we detected the effect of naringenin on platelet, a rich source of TGF-ß, both in vivo and in vitro. And we found that naringenin markedly decreased the TGF-ß level by inhibiting the activation of platelet. CONCLUSION: Our study showed that naringenin has a protective effect on thoracic aortic aneurysm formation in Marfan syndrome by suppressing both AT1 and TGF-ß signaling.

Association of Homocysteine and Risks of Long-Term Cardiovascular Events and All-Cause Death among Older Patients with Obstructive Sleep Apnea: A Prospective Study.

OBJECTIVES: This study aimed to assess whether raised baseline plasma tHcy concentrations increased the risks of major adverse cardiovascular events (MACE) and all-cause death outcomes in older patients with obstructive sleep apnea (OSA). DESIGN: A multicenter, prospective, observational study. SETTING: Beijing, Shandong Province, Gansu Province of China. PARTICIPANTS: A total of 1, 290 OSA patients aged 60 to 96 years from sleep centers of six hospitals in China consecutively recruited between January 2015 and October 2017. MEASUREMENTS: Cox proportional models assessed the association between tHcy and the risk of new-onset all events among Chinese older OSA patients. RESULTS: The final analysis (60.1% male; median age, 66 years) used data from 1, 100 subjects during a median follow-up of 42 months, a total of 105 (9.5%) patients developed MACE and 42 (3.8%) patients died. Multivariable Cox regression analysis showed higher adjusted hazard ratios (aHRs) of MACE, myocardial infarction (MI), hospitalization for unstable angina, and composite of all events with tHcy levels in the 4th quartile (HR=5.93, 95% CI: 2.79-12.59; HR=4.72, 95% CI:1.36-4.61; HR=4.26, 95% CI:1.62-5.71; HR=4.17, 95% CI:2.23-7.81) and the 3rd quartile (HR=3.79, 95% CI:1.76-8.20; HR=3.65, 95% CI:1.04-2.98; HR=2.75, 95% CI:1.08-3.76; HR=2.51, 95% CI:1.31-4.83) compared to reference tHcy levels in quartile 1, respectively, while the aHRs (95% CIs) of all-cause death showed significantly higher only in the highest tHcy level quartile than in the lowest quartile (HR=3.20, 95% CI=1.16-8.84, P=0.025) with no significant differences in risks of cardiovascular death and hospitalisation for heart failure among groups (P>0.05). CONCLUSIONS: tHcy, a marker of prognosis for older OSA patients, was significantly associated with the increased risk of MACE and all-cause death in this population independent of BMI, smoking status, and other potential risk factors, but not all clinical components events of MACE. New therapeutic approaches for older patients with OSA should mitigate tHcy-associated risks of MACE, and even all-cause death.

[Relationship between etiology and morphological classification of benign central airway stenosis and its prognosis].

Objectives: To analyze the relationship between etiology and morphological classification of benign central airway stenosis and its prognosis. Methods: We performed a retrospective study of the medical records of 453 patients initially diagnosed with benign airway stenosis at Department of Respiratory Diseases in Beijing Tiantan Hospital affiliated to Capital Medical University from January 2003 to October 2019. Of 453 patients, 260 were male. The age of the study population was 12-86(44.0±24.5) years. Results: Among the 453 patients diagnosed with benign central airway stenosis, 161 case (35.5%, including 113 post-tracheostomy tracheal stenosis and 48 post-intubation tracheal stenosis) were iatrogenic; 88 cases were from benign tumors (19.4%), 77 cases from tracheal or bronchial tuberculosis (17.0%), 71 case from tracheal foreign bodies (15.7%). Disease causes varied among different gender or age groups. The main type of stenosis was structural stenosis, of which 241 cases (53.2%) were intra-luminal and 183 cases (40.4%) were scar contracture type. The site of stenosis showed a certain relationship with the causes of stenosis. The stenosis degree was mainly from grade 2 to grade 4 (76.4%), and the length was mainly within 3 cm (84.8%). Single factor analysis on the relationship between disease cause, morphological classification and prognosis of benign central airway stenosis showed statistically better prognosis in groups that were caused by benign tumor, intraductal stenosis or stenosis that were 3-4 in degree and 1-2 degree in length. Conclusion: The common causes of central airway stenosis included iatrogenic stenosis, benign tumor, tracheal or bronchial tuberculosis and tracheal foreign bodies. Benign airway stenosis with different disease causes and morphological classification had different prognosis after bronchoscopic interventional treatment. Clinicians should know the disease causes, morphological characterization and risk factors for benign airway stenosis for earlier diagnosis, treatment or prevention.

[Clinical validation of the 2020 diagnostic approach for pediatric autoimmune encephalitis in a single center].

Objective: To evaluate the value of the 2020 diagnostic criteria (Cellucci criteria) for pediatric autoimmune encephalitis (AE) in children with suspected AE in a single center. Methods: The clinical data of 121 children hospitalized at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2021, with a diagnosis of suspected AE, were retrospectively collected and analyzed. The children were divided into definite antibody-positive AE (dAPAE), probable antibody-negative AE (prANAE), possible AE (pAE) and non-AE groups according to the Chinese expert consensus and the Graus criteria. A new diagnosis was made according to the Cellucci criteria which was compared with the clinical diagnosis to evaluate the diagnostic value of the Cellucci criteria. The Mann-Whitney U test, Kruskal-Wallis test, and χ2 test were used to compare the differences among groups. The sensitivity and specificity were used to evaluate efficacy of the Cellucci criteria. Results: Among the 121 children, 72 were males and 49 were females, with an age of 10.3 (6.5, 14.0) years at disease onset. There were 99 cases diagnosed as AE according the clinical diagnosis (58 males and 41 females), of which 43 cases were diagnosed as dAPAE, 14 cases as prANAE and 42 cases as pAE, and the other 22 cases were not AE (14 males and 8 females). The top 2 initial symptoms in the 99 children with AE were seizures (53 cases, 53.5%) and abnormal mental behaviors (35 cases, 35.4%). And the most common symptoms during the course of the disease were abnormal mental behaviors (77 cases, 77.8%) and seizures (64 cases, 64.6%). There were statistically differences in the incidence of consciousness disorders, autonomic dysfunctions during the course of the disease and the length of hospitalization among the 4 groups (χ2=21.63, 13.74, H=22.60, all P<0.05). Ninety-six of the 121 children were tested for AE-related antibodies, of which 45 cases (46.9%) were antibody-positive. According to the Cellucci criteria, 42 cases were diagnosed as dAPAE, 34 cases as prANAE and 14 cases as pAE. Compared with the clinical diagnosis, the sensitivity of the Cellucci criteria for the diagnosis of the 3 types of AE were 93.02%, 92.86% and 87.88%, and the specificity were 96.23%, 74.39% and 86.36%, respectively. Conclusions: The Cellucci criteria has a high sensitivity and specificity for the diagnosis of pAE and dAPAE in the clinical management of children with suspected AE, while a high sensitivity but low specificity for the diagnosis of prANAE. Therefore, it is recommended to apply the Cellucci criteria selectively in clinical practice according to the actual situation, especially in the diagnosis of prANAE.

The Drivers of the Martian Bow Shock Location: A Statistical Analysis of Mars Atmosphere and Volatile EvolutioN and Mars Express Observations.

The Martian interaction with the solar wind leads to the formation of a bow shock upstream of the planet. The shock dynamics appear complex, due to the combined influence of external and internal drivers. The extreme ultraviolet fluxes and magnetosonic Mach number are known major drivers of the shock location, while the influence of other possible drivers is less constrained or unknown such as crustal magnetic fields, solar wind dynamic pressure, or the Interplanetary Magnetic Field (IMF) intensity, and orientation. In this study, we compare the influence of the main drivers of the Martian shock location, based on several methods and published datasets from Mars Express (MEX) and Mars Atmosphere Volatile EvolutioN (MAVEN) missions. We include here the influence of the crustal fields, extreme ultraviolet fluxes, solar wind dynamic pressure, as well as (for MAVEN, thanks to magnetic field measurements) magnetosonic Mach number and Interplanetary Magnetic Field parameters (intensity and orientation angles). The bias due to the cross-correlations among the possible drivers is investigated with a partial correlations analysis. Several model selection methods (Akaike Information Criterion and Least Absolute Shrinkage Selection Operator regression) are also used to rank the relative importance of the physical parameters. We conclude that the major drivers of the shock location are extreme ultraviolet fluxes and magnetosonic Mach number, while crustal fields and solar wind dynamic pressure are secondary drivers at a similar level. The IMF orientation also plays a significant role, with larger distances for perpendicular shocks rather than parallel shocks.

Discrete Aurora at Mars: Dependence on Upstream Solar Wind Conditions.

Discrete aurora at Mars, characterized by their small spatial scale and tendency to form near strong crustal magnetic fields, are emissions produced by particle precipitation into the Martian upper atmosphere. Since 2014, Mars Atmosphere and Volatile EvolutioN's (MAVEN's) Imaging Ultraviolet Spectrograph (IUVS) has obtained a large collection of UV discrete aurora observations during its routine periapsis nightside limb scans. Initial analysis of these observations has shown that, near the strongest crustal magnetic fields in the southern hemisphere, the IUVS discrete aurora detection frequency is highly sensitive to the interplanetary magnetic field (IMF) clock angle. However, the role of other solar wind properties in controlling the discrete aurora detection frequency has not yet been determined. In this work, we use the IUVS discrete aurora observations, along with MAVEN observations of the upstream solar wind, to determine how the discrete aurora detection frequency varies with solar wind dynamic pressure, IMF strength, and IMF cone angle. We find that, outside of the strong crustal field region (SCFR) in the southern hemisphere, the aurora detection frequency is relatively insensitive to the IMF orientation, but significantly increases with solar wind dynamic pressure, and moderately increases with IMF strength. Interestingly however, although high solar wind dynamic pressures cause more aurora to form, they have little impact on the brightness of the auroral emissions. Alternatively, inside the SCFR, the detection frequency is only moderately dependent on the solar wind dynamic pressure, and is much more sensitive to the IMF clock and cone angles. In the SCFR, aurora are unlikely to occur when the IMF points near the radial or anti-radial directions when the cone angle (arccos(B x /|B|)) is less than 30° or between 120° and 150°. Together, these results provide the first comprehensive characterization of how upstream solar wind conditions affect the formation of discrete aurora at Mars.