Background
The liver manifestations of Alagille syndrome (ALGS) are highly variable, and factors affecting its prognosis are poorly understood. We asked whether the composition of bile acids in ALGS ...patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers.
Methods
Blood for bile acid profiling was collected from genetically confirmed
JAG1
-associated ALGS patients before one year of age. A good prognosis was defined as survival with native liver and total bilirubin (TB) < 85.5 μmol/L, while a poor prognosis was defined as either liver transplantation, death from liver failure, or TB ≥ 85.5 μmol/L at the last follow-up.
Results
We found that the concentrations of two poly-hydroxylated bile acids, tauro‐2β,3α,7α,12α-tetrahydroxylated bile acid (THBA) and glyco-hyocholic acid (GHCA), were significantly increased in patients with good prognosis compared to those with poor prognosis area under curve (AUC) = 0.836 and 0.782, respectively in the discovery cohort. The same trend was also observed in the molar ratios of GHCA to glyco- chenodeoxycholic acid (GCDCA) and tetrahydroxylated bile acid (THCA) to tauro-chenodeoxycholic acid (TCDCA) (both AUC = 0.836). A validation cohort confirmed these findings. Notably, tauro‐2β,3α,7α,12α-THBA achieved the highest prediction accuracy of 88.00% (92.31% sensitivity and 83.33% specificity); GHCA at > 607.69 nmol/L was associated with native liver survival hazard ratio: 13.03, 95% confidence interval (CI): (2.662–63.753),
P
= 0.002.
Conclusions
We identified two poly-hydroxylated bile acids as liver prognostic biomarkers of ALGS patients. Enhanced hydroxylation of bile acids may result in better clinical outcomes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. ...This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study.
All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II.
Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively.
Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.
This study reports a case of Unilateral Endogenous Fungal Endophthalmitis After Esophageal Cancer Surgery.
One patient presented with a month-long loss of vision in his left eye, he had surgery for ...esophageal cancer 2 months earlier. The patient underwent cataract surgery (by phacoemulsification) in the left eye combined with 25-gauge vitrectomy and silicone oil tamponade. The microbiological culture pointed to infection with Candida albicans. At 3-month follow-up, the unaided visual acuity of left eye was 0.02 and corrected visual acuity was 0.2. In addition, there was no recurrence of the endophthalmitis within 1 year of the surgery.
The early diagnosis of endogenous fungal endophthalmitis is difficult, and the disease is very likely to be misdiagnosed as uveitis. It is therefore critical to improve awareness of this condition and to reduce the incidence of its misdiagnosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The electrification level of commercial vehicles in China has achieved remarkable development with the support of fiscal and tax policies. In this paper, 15 major cities are selected as samples, and ...the combined effect of national and local fiscal and tax policies is carefully assessed using the DEA model. The results show that: (1) the comprehensive efficiency of the sample cities is high, indicating that the current policy portfolio has achieved great efficiency in general. (2) Shenzhen, Chengdu and Shanghai are taking the lead in the promotion and penetration of new energy trucks, but the 3 cities fail to achieve the best overall efficiency, with lower scale efficiency and diminished returns to scale. (3) Most of the cities suffer input redundancy, and should further optimize the policy structure and synergy to ensure the efficient implementation of various policies.
Benzoapyrene (BaP), a representative polycyclic aromatic hydrocarbon, exists widely in automobile emissions and polluted atmosphere. The current study aimed to describe pulmonary inflammation during ...BaP-induced acute lung injury (ALI). All mice except controls were intratracheally instilled with a single dose of BaP (90 μg per mouse). The alveolar structure was damaged, accompanied by numerous inflammatory cell infiltration around pulmonary interstitium and small airway. Airway wall area and mean linear intercept were reduced in BaP-exposed mouse lungs. By contrast, airway wall thickness and destructive index were elevated in BaP-exposed mouse lungs. Several inflammatory genes, such as
Tnf-α
,
Il-1β
,
Il-6
,
Mip-2
,
Kc
, and
Mcp-1
, were upregulated in mouse lungs. Phosphorylated IκBα was elevated in BaP-exposed mouse lungs. Nuclear translocation of NF-κB p65 and p50 was accordingly observed in BaP-exposed mouse lungs. Several molecules of the MAPK pathway, including JNK, ERK1/2, and p38, were activated in mouse lungs. Of interest, pretreatment with N-acetylcysteine (NAC), an antioxidant, alleviated BaP-induced ALI. Moreover, NAC attenuated BaP-induced inflammatory cell infiltration in mouse lungs and inflammatory gene upregulation in A549 cells. In addition, NAC attenuated BaP-induced NF-κB activation in A549 cells and mouse lungs. These results suggest that NAC alleviates pulmonary inflammatory response during BaP-evoked ALI.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Inflammation of the fetal membranes is an indispensable event of labor onset at both term and preterm birth. Interleukin-33 (IL-33) is known to participate in inflammation via ST2 (suppression of ...tumorigenicity 2) receptor as an inflammatory cytokine. However, it remains unknown whether IL-33/ST2 axis exists in human fetal membranes to promote inflammatory reactions in parturition.
The presence of IL-33 and ST2 and their changes at parturition were examined with transcriptomic sequencing, quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry in human amnion obtained from term and preterm birth with or without labor. Cultured primary human amnion fibroblasts were utilized to investigate the regulation and the role of IL-33/ST2 axis in the inflammation reactions. A mouse model was used to further study the role of IL-33 in parturition.
Although IL-33 and ST2 expression were detected in both epithelial and fibroblast cells of human amnion, they are more abundant in amnion fibroblasts. Their abundance increased significantly in the amnion at both term and preterm birth with labor. Lipopolysaccharide, serum amyloid A1 and IL-1β, the inflammatory mediators pertinent to labor onset, could all induce IL-33 expression through NF-κB activation in human amnion fibroblasts. In turn, via ST2 receptor, IL-33 induced the production of IL-1β, IL-6 and PGE2 in human amnion fibroblasts via the MAPKs-NF-κB pathway. Moreover, IL-33 administration induced preterm birth in mice.
IL-33/ST2 axis is present in human amnion fibroblasts, which is activated in both term and preterm labor. Activation of this axis leads to increased production of inflammatory factors pertinent to parturition, and results in preterm birth. Targeting the IL-33/ST2 axis may have potential value in the treatment of preterm birth.
Introduction
Several reports have noted that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced lymphopenia in coronavirus disease 2019 (COVID-19) patients. However, the clinical ...significance of lymphopenia remains unclear. The objective of this study was to analyze the association between lymphopenia at an early stage and the prognosis of COVID-19 patients.
Material and methods
All 192 hospitalized patients with COVID-19 were enrolled. Demographic data and clinical characteristics were collected and patient’s prognosis was followed up.
Results
On admission, 84 (43.8%) patients suffered from lymphopenia among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among patients over 70 years old than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphopenia. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphopenia. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphopenia. Moreover, total bilirubin (TBIL) and direct bilirubin (DBIL), two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphopenia. Among 84 COVID-19 patients with lymphopenia, 32.1% died. The fatality rate was obviously higher in COVID-19 patients with lymphopenia.
Conclusions
Older COVID-19 patients are more susceptible to lymphopenia. Multiple organ injuries were more serious in COVID-19 patients with lymphopenia. Lymphopenia at an early stage aggravates the severity and elevates the death risk of COVID-19 patients.
Abstract
Objective
To describe the temporal trend of the number of new congenital heart disease (CHD) cases among newborns in Jinhua from 2019 to 2020 and explored an appropriate model to fit and ...forecast the tendency of CHD.
Methods
Data on CHD from 2019 to 2020 was collected from a health information system. We counted the number of newborns with CHD weekly and separately used the additive Holt-Winters ES method and ARIMA model to fit and predict the number of CHD for newborns in Jinhua. By comparing the mean square error, rooted mean square error and mean absolute percentage error of each approach, we evaluated the effects of different approaches for predicting the number of CHD in newborns.
Results
A total of 1135 newborns, including 601 baby girls and 534 baby boys, were admitted for CHD from HIS in Jinhua during the 2-year study period. The prevalence of CHD among newborns in Jinhua in 2019 was 0.96%. Atrial septal defect was diagnosed the most frequently among all newborns with CHD. The number of CHD cases among newborns remained stable in 2019 and 2020. There were fewer cases in spring and summer, while cases peaked in November and December. The ARIMA(2,1,1) model relatively offered advantages over the additive Holt-winters ES method in predicting the number of newborns with CHD, while the accuracy of ARIMA(2,1,1) was not very ideal.
Conclusions
The diagnosis of CHD is related to many risk factors, therefore, when using temporal models to fit and predict the data, we must consider such factors’ influence and try to incorporate them into the models.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cognitive dysfunction is common in hypothyroid patients, even after undergoing sufficient levothyroxine (LT4) replacement therapy for euthyroid. Our previous studies indicated that cholinergic ...neurons might contribute to the decline of cognition in adult-onset hypothyroidism. Nevertheless, the role of the cellular and neural control of basal forebrain (BF) cholinergic neurons in hypothyroidism-induced cognitive impairments is unknown. Using transgenic mice that specifically expressed chemogenetic activators in their BF cholinergic neurons, we systematically investigated the role of BF cholinergic neurons in hypothyroidism-induced cognitive dysfunction by the combined approaches of patch clamp electrophysiology, behavioral testing, and immunohistochemistry. The results showed that LT4 treatment in the adult-onset hypothyroid mice reversed only 78 % of the BF cholinergic neurons to their normal values of electrophysiological properties. LT4 monotherapy did not rehabilitate cognitive function in the hypothyroid mice. Chemogenetic selective activation of the BF cholinergic neurons combined with LT4 treatment significantly improved learning and memory functions in the hypothyroid mice. In addition, chemogenetic activation of the cholinergic neurons induced the robust expression of c-Fos protein in the BF, prefrontal cortex (PFC), and hippocampus. This indicated that the BF cholinergic neurons improved learning and memory functions in the hypothyroid mice via the BF-PFC and BF-hippocampus pathways. In the hypothyroid C57BL/6 J mice, combined treatment via LT4 and donepezil, a cholinesterase inhibitor, significantly increased cognitive functions. The results suggested that the BF cholinergic neurons are critical for regulating learning and memory and reveal a novel pathophysiological mechanism for hypothyroidism-induced cognitive impairments.
Display omitted
•Basal forebrain cholinergic neurons are selectively dysfunctional in hypothyroid mice.•Activation of basal forebrain cholinergic neurons increased cognitive function in levothyroxine-treated hypothyroid mice.•Co-administration of donepezil and levothyroxine improved the cognitive function of hypothyroid mice.
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Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Pre-eclampsia (PE) is the main cause of death in maternal and prenatal morbidity. No effective clinical tools could be used for the prediction of PE. A radiomics nomogram based on ...diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps was established to predict PE from gestational hypertension (GH).
Materials and methods
A total of 138 patients with hypertensive disorders of pregnancy were continuously enrolled in the study prospectively, namely, 58 patients with PE and 80 patients with GH. The patients were randomly divided into a training cohort (
n
= 97) and a test cohort (
n
= 41). Radiomics features were extracted from DWI and ADC maps. The radiomics signature was constructed using a least absolute shrinkage and selection operator (LASSO) algorithm in the training cohort. A radiomics nomogram was developed by combining the radiomics signature with the selected clinical risk factors. The area under the receiver operating characteristic (ROC) curves (AUC), specificity, sensitivity, accuracy, positive predictive value, and negative predictive values of the radiomics signature, clinical risk factors, and radiomics nomogram were calculated. Decision curve analysis (DCA) was performed to determine the clinical usefulness of the radiomics nomogram.
Results
The LASSO analysis finally included 11 radiomics features, which were defined as the radiomics signature. The individualized prediction nomogram was constructed by integrating the radiomics signature, maternal age, and body mass index (BMI). The nomogram exhibited a good performance both in the training cohort AUC of 0.89 (95% CI, 0.82–0.95) and test cohort AUC of 0.85 (95% CI, 0.73–0.97) for predicting PE from GH. The DCA indicated that clinicians and patients could benefit from the use of radiomics nomogram.
Conclusion
The radiomics nomogram could individually predict PE from GH. The nomogram could be conveniently used to facilitate the treatment decision for clinicians and patients.
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