Single-cell RNA sequencing reveals that NRF2 regulates vascular smooth muscle cell phenotypic switching in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a life-threatening disease characterized by extensive membrane destruction in the vascular wall that is closely associated with vascular smooth muscle cell (VSMC) phenotypic switching. A thorough understanding of the changes in regulatory factors during VSMC phenotypic switching is essential for managing AAA therapy. In this study, we revealed the impact of NRF2 on the modulation of VSMC phenotype and the development of AAA based on single-cell RNA sequencing analysis. By utilizing a murine model of VSMC-specific knockout of nuclear factor E2-related factor 2 (NRF2), we observed that the absence of NRF2 in VSMCs exacerbated AAA formation in an angiotensin II-induced AAA model. The downregulation of NRF2 promoted VSMC phenotypic switching, leading to an enhanced inflammatory response. Through genome-wide transcriptome analysis and loss- or gain-of-function experiments, we discovered that NRF2 upregulated the expression of VSMC contractile phenotype-specific genes by facilitating microRNA-145 (miR-145) expression. Our data identified NRF2 as a novel regulator involved in maintaining the VSMC contractile phenotype while also influencing AAA formation through an miR-145-dependent regulatory mechanism.

Non-linear relationship between red blood cell distribution width and gastrointestinal bleeding risk in stroke patients: results from multi-center ICUs.

Background: The red blood cell distribution width (RDW) is closely linked to the prognosis of multiple diseases. However, the connection between RDW and gastrointestinal bleeding (GIB) in stroke patients is not well understood. This study aimed to clarify this association. Methods: This retrospective study involved 11,107 hospitalized patients from 208 hospitals in the United States, admitted between January 1, 2014, and December 31, 2015. We examined clinical data from 7,512 stroke patients in the intensive care unit (ICU). Multivariate logistic regression assessed the link between RDW and in-hospital GIB in stroke patients. Generalized additive model (GAM) and smooth curve fitting (penalty spline method) were utilized to explore the non-linear relationship between RDW and GIB in stroke patients. The inflection point was calculated using a recursive algorithm, and interactions between different variables were assessed through subgroup analyses. Results: Among the 11,107 screened stroke patients, 7,512 were included in the primary analysis, with 190 identified as having GIB. The participants had a mean age of (61.67 ± 12.42) years, and a median RDW of 13.9%. Multiple logistic analysis revealed RDW as a risk factor for in-hospital GIB in stroke patients (OR = 1.28, 95% CI 1.21, 1.36, p < 0.05). The relationship between RDW and in-hospital GIB in stroke patients was found to be non-linear. Additionally, the inflection point of RDW was 14.0%. When RDW was ≥14.0%, there was a positive association with the risk of GIB (OR: 1.24, 95% CI: 1.16, 1.33, p < 0.0001). Conversely, when RDW was <14.0%, this association was not significant (OR: 1.02, 95% CI: 0.97-1.07, p = 0.4040). Conclusion: This study showed a substantial non-linear link between RDW and the risk of GIB in stroke patients. Maintaining the patient's RDW value below 14.0% could lower the risk of in-hospital GIB.

Correction: Establishment of a prediction model for prehospital return of spontaneous circulation in out-of-hospital patients with cardiac arrest.

[This corrects the article on p. 508 in vol. 15, PMID: 37900904.].

Non-linear relationship between pulse pressure and the risk of prediabetes: a 5-year cohort study in Chinese adults.

Previous research has established a strong link between pulse pressure (PP) and diabetes, but there is limited investigation into the connection between PP and prediabetes. This study aims to explore the potential association between PP and prediabetes. A retrospective cohort study encompassed 202,320 Chinese adults who underwent health check-ups between 2010 and 2016. Prediabetes was defined in accordance with the World Health Organization criteria, indicating impaired fasting glucose, with fasting blood glucose levels ranging from 6.1 to 6.9 mmol/L. To assess the PP-prediabetes relationship, we employed Cox regression analysis, sensitivity analysis, and subgroup analysis. Cox proportional hazards regression, coupled with cubic spline functions and smooth curve fitting, helped elucidate the non-linear PP-prediabetes relationship. Upon adjusting for confounding factors, we observed a positive association between PP and prediabetes (HR 1.15, 95% CI 1.11-1.18, P < 0.0001). Participants in the fourth quartile (PP ≥ 51 mmHg) had a 73% higher likelihood of developing prediabetes compared to those in the first quartile (PP < 36 mmHg) (HR 1.73, 95% CI 1.52-1.97, P < 0.0001). Moreover, the relationship between PP and prediabetes was non-linear. A two-piece Cox proportional hazards regression model identified an inflection point at 40 mmHg for PP (P for log-likelihood ratio test = 0.047). Sensitivity and subgroup analyses corroborated the robustness of our findings. Our study reveals a non-linear correlation between PP and prediabetes, signifying an increased risk of prediabetes when PP levels exceed 40 mmHg. This discovery has significant clinical implications for early prediabetes prevention and intervention, ultimately contributing to improved patient outcomes and quality of life.

Elevated platelet count is associated with decreased mortality from hemorrhagic stroke in hospital: a multi-center retrospective cohort study.

This study aimed to investigate the relationship between platelet count (PC) and mortality in patients with hemorrhagic stroke (HS). The research reviewed data from 10,466 patients hospitalized in 208 hospitals in the United States from January 1, 2014, to December 31, 2015. Of these, 3262 HS patients were included in the primary analysis for those admitted to the intensive care unit (ICU). The average age of these patients was 67.05 years, with 52.79% being male. The median PC was (221.67 ± 73.78) × 109/L. Multivariate logistic regression analysis revealed that PC was a protective factor for mortality in HS patients (OR = 0.98, 95% CI 0.97-1.00, P < 0.05). Additionally, a non-linear association between PC and mortality in HS patients was found using a generalized additive model (GAM) and smooth curve fitting (penalty spline method). For the first time, a recursive algorithm identified the inflection point of platelet count as 194 × 109/L. On the left side of the inflection point, for every increase of 10 units in platelet count, the mortality rate of HS patients decreases by 10%. The study demonstrates a non-linear relationship between PC and the risk of mortality in HS patients. A platelet counts higher than the inflection point (194 × 109/L) may be a significant intervention to reduce mortality in HS patients.

Age-related changes in the bottom view area of ancient children's skulls from the Zaghunluq Cemetery in Xinjiang, China.

This study examined forty skull samples of ancient children, aged 2-15 years, excavated from the Zaghunluq cemetery in Xinjiang, China. The purpose of the study was to analyze the patterns of age-related physiological development and growth spurts in the skulls of these ancient children by comparing the projected areas of the bottom view of the skull, the occipital bone, and the maxilla among different age groups. The analysis of variance (ANOVA) revealed significant differences in the projected areas of the skull's bottom view, occipital bone, and maxilla among five age groups (2 years old, 3-5 years old, 6-8 years old, 9-11 years old, and 12-15 years old). The growth spurts in the projected area of the occipital bone occurred at ages 3-5 years and 6-8 years. As for the maxilla, the growth spurts took place at ages 6-8 years and 12-15 years. Meanwhile, the projected area of the skull's bottom view exhibited a continuous increase without any periods of rapid growth. These findings may reflect the patterns of age-related growth in the skulls of ancient children in Xinjiang, China.

Establishment of a prediction model for prehospital return of spontaneous circulation in out-of-hospital patients with cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death worldwide. AIM: To explore factors influencing prehospital return of spontaneous circulation (P-ROSC) in patients with OHCA and develop a nomogram prediction model. METHODS: Clinical data of patients with OHCA in Shenzhen, China, from January 2012 to December 2019 were retrospectively analyzed. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were applied to select the optimal factors predicting P-ROSC in patients with OHCA. A nomogram prediction model was established based on these influencing factors. Discrimination and calibration were assessed using receiver operating characteristic (ROC) and calibration curves. Decision curve analysis (DCA) was used to evaluate the model's clinical utility. RESULTS: Among the included 2685 patients with OHCA, the P-ROSC incidence was 5.8%. LASSO and multivariate logistic regression analyses showed that age, bystander cardiopulmonary resuscitation (CPR), initial rhythm, CPR duration, ventilation mode, and pathogenesis were independent factors influencing P-ROSC in these patients. The area under the ROC was 0.963. The calibration plot demonstrated that the predicted P-ROSC model was concordant with the actual P-ROSC. The good clinical usability of the prediction model was confirmed using DCA. CONCLUSION: The nomogram prediction model could effectively predict the probability of P-ROSC in patients with OHCA.

Age-related changes in the endocranial capacity and surface area of ancient children from the Zaghunluq Cemetery (650-150 BCE) in Xinjiang, Northwestern China.

Early childhood is an important period for the rapid growth of the brain, which is crucial to neural connection and cognitive development. The purpose of this study is to characterize the age changes of endocasts in ancient children in Northwestern China (2600-2100 BP) to enrich our understanding of brain growth. 28 crania of ancient children excavated from the Zaghunluq cemetery were analyzed using endocasts generated from CT images. The endocast features of age-related changes were assessed by comparing the endocranial volume (cranial capacity), the intracranial surface area, and their ratios among different age groups: 2, 3-5, 6-7, 8-10, 12-15, and 17-19 years. The results demonstrated that with the increase of age, the volume and the surface area of children's endocasts seem to increase between age groups. The growth spurt periods of endocranial volume are 3-5 years old and 8-10 years old, and the growth spurt period of endocranial surface area is 3-5 years old, similar to the patterns in modern children. The increase of endocast surface area is smaller than that of volume, resulting in an overall increase in the ratio of endocranial volume to surface area, indicating a trend of gradual globularization of the brain.

Delayed closure of the anterior fontanelle in Iron Age children from Zaghunluq, northwestern China.

Delayed closure of the anterior fontanelle is often associated with various disorders. However, the phenomenon might be a normal variation. In this study, the anterior fontanelle was investigated in children from the Iron Age Zaghunluq cemetery in Xinjiang, northwestern China. Age at death was estimated by tooth development/eruption in the children. The anterior fontanelle was visually assessed for delayed fusion. Three out of nine children aged between 3-6 years old from the cemetery had signs of open anterior fontanelle. However, there were no signs of craniofacial pathology or developmental disruption. Delayed closure of the anterior fontanelle might have been a norm in the Iron Age Zaghunluq population. However, it is impossible to determine the reasons behind the high prevalence of delayed AF closure at Zaghunluq. Additional studies are warranted to determine whether this phenomenon is population specific, or diet specific, or just an individual variation.

Flow-Mediated Dilatation in the Assessment of Coronary Heart Disease: A Meta-Analysis.

Endothelial dysfunction may contribute to the increased morbidity and mortality associated with coronary heart disease (CHD). Flow-mediated dilatation (FMD) is the most popular noninvasive method for vascular endothelial function evaluation. This meta-analysis aimed to investigate the association between FMD and CHD. We searched the publications listed in the PubMed, Web of Science, Scopus, and Embase databases. Stata 14 software was used to analyze the data. Standardized mean difference (SMD) was used to calculate FMD levels, and the effect sizes were expressed with a 95% confidence interval (CI). I2 statistics were used to evaluate statistical heterogeneity. In this meta-analysis, 9 studies enrolled a total number of 943 participants, including 534 (56.63%) patients with CHD and 409 controls (43.37%). We found that patients with CHD showed a significantly lower FMD than the controls (SMD -0.706%; 95% CI: -0.985, -0.427; P=0.001) with high heterogeneity. In addition, funnel plot analysis suggested asymmetry that could be evidence of publication bias. But sensitivity analyses show that there were no influential studies. This meta-analysis provides evidence that patients with CHD show a significantly lower FMD than controls and highlights the literature on FMD as a hallmark in CHD diseases.

Metastatic cancer along ancient Silk Road: A possible case from Xinjiang (China).

OBJECTIVE: Palaeopathological evidence of cancer, especially metastatic cancer, is rare in China. This paper describes and diagnoses a cranium with multiple lytic lesions recovered from the Sampula cemetery in Xinjiang, attempting to diagnose the type of disease that could have caused the pathological lesions observed. MATERIAL: A cranium from an adult male (#00106) was recovered from the Sampula cemetery (dated to 55 BCE to 335 CE) located in the Luopu County, the Hotan River oasis on the southern edge of the Tarim Basin in southern Xinjiang. METHODS: The cranium was assessed macroscopically and radiographically (CT). RESULTS: Multiple osteolytic lesions with irregular and "moth-eaten" margins were detected in cranium #00106. CT scans revealed the development of the lesions began at the diploe and identified a "button sequestrum". CONCLUSIONS: Based on lesion characteristics, metastatic carcinoma was likely the cause of lesions found in cranium #00106. SIGNIFICANCE: This case has expanded our knowledge of the malignant neoplasms of ancient populations in northwest China and discusses the possible risk factors in the occurrence of cancer in the Sampula site, as well as the possible impacts of skeletal metastases on the individual. LIMITATIONS: The distribution of osteolytic lesions over the complete skeleton cannot be observed because of the unavailability of postcranial bone. SUGGESTIONS FOR FUTURE RESEARCH: With the increasing number of reports describing diseases in ancient China, the patterns of diseases occurrence and development can be further explored from spatial and temporal perspectives.

Anthropometrical Analysis of the Foramen Magnum in Ancient Children.

ABSTRACT: Anthropometrical analysis of the foramen magnum (FM) was conducted on a sample of 32 children and 101 adults excavated from Zaghunluq cemetery dating between 2600 and 1900 cal. yr BP in Xinjiang, China. The FM features of children during age changes and growth spurt periods were explored by comparing the length of the FM, the width of the FM, and the values of the FM index among different age groups. The data presented in this study indicate that the size of the FM was smallest at 2 years old, and the FM size during 5 to 7 years of age was close to that of adults, supporting the view that the size of the 6-year-old skull is close to that of the adult and brain growth appears to terminate at 7 years. The FM likely experiences a growth spurt period during 2 to 5 years of age. Regression equations were established by regression analysis of the length and width of the FM. Study on the morphological variation of the FM provides further information about the growth of children.

Age-Related Changes in Orbits of Ancient Children from Zaghunluq Cemetery in Xinjiang, China.

Thirty-eight skull samples of ancient children were analyzed that were excavated from the Zaghunluq cemetery, which dates between 2600 and 1900 cal yr BP. The orbit features of children during age changes and growth spurt periods were explored by comparing the orbital height, orbital breadth, orbital area, orbital index, and other measurements among different age groups: 2 years, 3-5 years, 6-8 years, 9-11 years, and 12-15 years. The analysis showed significant differences in orbital breadth across the five age groups, while differences in orbital height, orbital area, and orbital index were not significant. The growth spurt period of orbital breadth I was during 3-5 years of age, and the growth spurt period of orbital breadth II occurred during 6-8 years. Notably, the orbital height of a 2-year-old child has reached 92.7% of adult size. This may elucidate changes in the orbits of children due to age in ancient Xinjiang, China.

NF-κB mediates early blood-brain barrier disruption in a rat model of traumatic shock.

BACKGROUND: Blood-brain barrier (BBB) disruption is associated with a large number of central nervous system and systemic disorders. The aim of the present study was to investigate the dynamic change of BBB changes during traumatic shock and resuscitation as well as the mechanisms involved. METHODS: The experiments were performed on male Sprague-Dawley rats anesthetized with pentobarbital sodium. To produce traumatic shock, the rats were subjected to bilateral femoral traumatic fracture and blood withdrawal from the femoral artery to decrease mean arterial pressure (MAP) to 35 mm Hg. Hypovolemic status (at a MAP of 35 to 40 mm Hg) was sustained for 1 hour followed by fluid resuscitation with shed blood and 20 mL/kg of lactated Ringer's solution. RESULTS: The rats were sacrificed at 1 hour, 2 hours, or 6 hours after fluid resuscitation. Blood-brain barrier permeability studies showed that traumatic shock significantly increased brain water contents and sodium fluorescein leakage, which was aggravated by fluid resuscitation. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses revealed that Na-K-Cl cotransporter-1 and vascular endothelial growth factor (VEGF) expression were upregulated in cortical brain tissue of traumatic shock rats, and this change was accompanied by downregulation of occludin and claudin-5. Traumatic shock also significantly increased the protein levels of NF-κB-p65 subunit. Of note, administration of NF-κB inhibitor PDTC effectively attenuated augmentation of the above changes. CONCLUSION: Our results suggest that traumatic shock is associated with early BBB disruption, and inhibition of NF-κB may be an effective therapeutic strategy in protecting the BBB under traumatic shock conditions.

[Analysis of clinical characteristic of 158 inpatients with dengue fever in Guangzhou area during the 2014 epidemic].

OBJECTIVE: To investigate the clinical characteristics of the inpatients suffering from dengue fever in order to provide references for better diagnosis and treatment. METHODS: The clinical data of 158 dengue fever patients admitted to the First Affiliated Hospital of Sun Yat-Sen University from July 23rd to October 31st, 2014 during the 2014 epidemic in Guangzhou area were retrospectively analyzed, including general clinical manifestations, conventional examinations, pathogenesis, and prognosis. RESULTS: The mean age of the 158 patients was ( 56 ± 20 ) years, with half of them over 60 years old (79 cases). Among them, 94 (59.49%) were male. (1) The common manifestations included fever (100%), headache (70.89%), myalgia/bone soreness (62.03%), and skin rash (54.43%). Bleeding and plasma leakage were found in 25.95% and 14.56% of the patients respectively. (2) Laboratory examination: leucopenia (75.32%) and thrombocytopenia (77.85%) were found, and alanine aminotransferase (ALT) and aspartate aminotransferase ( AST ) were elevated in 57.59% and 77.85% of the patients respectively. However, elevation of blood hematocrit was rare (1.27% ). (3) It was found that in the acute phase (0 - 5 days of the onset), serum dengue virus antibody IgM (DF-IgM) was positive in 63.54% of the patients (61/96), and 92.62% (113/122) of patients were dengue virus RNA ( DENA-RNA ) positive. (4) The rate of comorbidity in this study was 55.06% ( 87/158 ), including hypertension (27.22%) and type 2 diabetes (15.82%), which were the two most common co-morbidities. (5) All the patients were given supportive therapy to prevent complications. They were also isolated for more than 5 days after onset, and at least for 24 hours after subsidence of fever in addition. (6) The criteria for the diagnosis of severe dengue were fulfilled in 18 patients (11.39%). One patient died of massive hemorrhage from gastro-intestinal tract, and 1 patient voluntarily left hospital with untreated multiple organ dysfunction syndrome (MODS). Another 2 patients of dengue fever died from primary cardio-cerebrovascular disease, and the remaining 154 patients (97.47%) fully recovered with supportive therapy and complication prevention measures. CONCLUSIONS: The clinical manifestations of inpatients with dengue fever in this study were typical, and they manifested a higher incidence of severe illness. DENA-RNA could be a sensitive indicator for early pathogenic diagnosis. With symptomatic and supportive therapy, most patients had a good outcome. However, early diagnosis and clinical interventions of severe dengue still need further studies.