Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.

Photochromic radical states in 3D covalent organic frameworks with zyg topology for enhanced photocatalysis.

Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination. Here, we develop a novel strategy by combining [6 + 4] nodes to construct zyg-type 3D COFs, first reported in COF chemistry. This structure type exhibits a fused Olympic-rings-like shape, which provides a platform for stabilizing the photoinduced D-A radical pairs. The zyg-type COFs containing catalytically active moieties such as triphenylamine and phenothiazine (PTZ) show superior photocatalytic production rates of hydrogen peroxide (H2O2). Significantly, the photochromic radical states of these COFs show up to 400% enhancement in photocatalytic activity compared to the parent states, achieving a remarkable H2O2 synthesis rate of 3324 µmol g-1 h-1, which makes the PTZ-COF one of the best crystalline porous photocatalysts in H2O2 production. This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.

Functional conservation of GENOMES UNCOUPLED1 in plastid-to-nucleus retrograde signaling in tomato.

Retrograde signaling between plastids and the nucleus is vital for chloroplast biogenesis and environmental responses. GENOMES UNCOUPLED1 (GUN1) was proposed to be a central integrator of multiple retrograde signaling pathways in the model plant Arabidopsis thaliana (Arabidopsis). However, the function of GUN1 orthologs in other plant species has not been well studied. Here, we found that many GUN1 orthologs from the Solanaceae family have a short N-terminus before the first pentatricopeptide repeat (PPR) motif which is predicted as intrinsically disordered regions (IDRs). Functional analyses of tomato (Solanum lycopersicum L.) GUN1 (SlGUN1), which does not contain N-terminal IDRs, show that it can complement the GUN phenotype of the Arabidopsis gun1 mutant (Atgun1). However, in contrast to the AtGUN1 protein, which does contain the N-terminal IDRs, the SlGUN1 protein is highly accumulated even after chloroplast biogenesis is completed, suggesting that the N-terminal IDRs may determine the stability of the GUN1 protein. Furthermore, we generated tomato Slgun1 genome-edited mutants via the CRISPR-Cas9 system. The Slgun1 mutants exhibited a typical GUN phenotype under lincomycin (Lin) or norflurazon (NF) treatment. Moreover, Slgun1 mutants are hypersensitive to low concentrations of Lin or NF. Taken together, our results suggest that, although lacking the N-terminal IDRs, SlGUN1 plays conserved roles in plastid retrograde signaling in tomato plants.

Association of intestinal microecology with the development and progression of autoimmune hepatitis / 临床肝胆病杂志

Autoimmune hepatitis （AIH） is an autoimmune disease characterized by chronic liver inflammation， with a gradually increasing incidence rate， and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years， it has been believed that changes in intestinal microecology can cause changes in autoimmune state， microbial metabolites， and intestinal barrier， which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients， elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH， and briefly describes related treatment regimens from the perspective of intestinal microecology， so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis， diagnosis， and treatment of AIH.

On-Off Switching of a Photocatalytic Overall Reaction through Dynamic Spin-State Transition in a Hofmann Clathrate System.

Spin-state transition is a vital factor that dominates catalytic processes, but unveiling its mechanism still faces the great challenge of the lack of catalyst model systems. Herein, we propose that the {Fe-Pt} Hofmann clathrates, whose dynamic spin-state transition of metal centers can be chemically manipulated through iodine treatment, can serve as model systems in the spin-related structural-catalytic relationship study. Taking the photocatalytic synthesis of H2O2 as the basic catalytic reaction, when the spin state of Fe(II) in the clathrate is high spin (HS), sacrificial agents are indispensable to the photosynthesis of H2O2 because only the photocatalytic oxygen reduction reaction (ORR) occurs; when it is low spin (LS), both the ORR and water oxidation reaction (WOR) can take place, enabling a high H2O2 photosynthesis rate of 66 000 µM g-1 h-1 under visible-light irradiation. In situ characterizations combined with density functional theory calculations confirmed that, compared with the HS-state counterpart, the LS state can induce strong charge transfer between the LS Fe(II) and the iodide-coordinating Pt(IV) in the polymer and reduce the energy barriers for both the ORR and WOR processes, dominating the on-off switching upon the photosynthesis of H2O2 in O2-saturated water. What's more, the one-pot tandem reactions were conducted to utilize the synthesized H2O2 for transforming the low-value-added sodium alkenesulfonates into value-added bromohydrin products with decent conversion rates. This work provides a pioneering investigation into on-off switching the photocatalytic overall reaction through manipulating the metallic spin-state transition in spin-crossover systems.

Preservation of the pectoralis major fascia has no impact on the long-term oncologic outcomes of patients with breast cancer treated with conservative mastectomy and immediate breast reconstruction: A propensity score matching analysis.

BACKGROUND: The oncologic safety of preserving the pectoralis major fascia (PMF) in patients with breast cancer remains controversial. In this study, we aimed to determine the impact of preserving the PMF on long-term oncologic outcomes in patients with breast cancer treated with immediate implant-based breast reconstruction (IBBR) following conservative mastectomy. METHODS: We selected women with early-stage breast cancer who underwent conservative mastectomy and submuscular IBBR in our center during 2014-2019. The propensity score matching method was used to create well-balanced fascia-preserved and fascia-removed groups. Locoregional recurrence-free survival (LRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the fascia-preserved and fascia-removed groups. RESULTS: After matching, there were 219 patients in each group. The mean follow-up time was 64.8 ± 18.1 months for the fascia-preserved group and 64.9 ± 18.4 months for the fascia-removed group. There were no significant differences between the groups in terms of LRFS (91.3% vs. 93.8%; p = 0.818), DMFS (94.0% vs. 92.3%; p = 0.056), DFS (89.9% vs. 88.4%; p = 0.261), and OS (95.8% vs. 95.4%; p = 0.783) rates. In the fascia-preserved group, 61.5% of the locoregional recurrence events occurred within 2 years after surgery. CONCLUSION: Preservation of the PMF did not significantly impact the long-term oncologic outcomes in patients with breast cancer who underwent conservative mastectomy and IBBR. The PMF might be safely preserved in patients without suspicious tumor invasion into this fascia.

Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy.

Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher's test, p = 2.02 × 10-6, adjusted α = 4.52 × 10-6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.

Metabolic engineering of Escherichia coli for efficient production of l-arginine.

As a semi-essential amino acid, l-arginine (l-Arg) plays an important role in food, health care, and medical treatment. At present, the main method of producing l-Arg is the use of microbial fermentation. Therefore, the selection and breeding of high-efficiency microbial strains is the top priority. To continuously improve the l-Arg production performance of the strains, a series of metabolic engineering strategies have been tried to transform the strains. The production of l-Arg by metabolically engineered Corynebacterium glutamicum (C. glutamicum) reached a relatively high level. Escherichia coli (E. coli), as a strain with great potential for l-Arg production, also has a large number of research strategies aimed at screening effective E. coli for producing l-Arg. E. coli also has a number of advantages over C. glutamicum in producing l-Arg. Therefore, it is of great significance to screen out excellent and stable E. coli to produce l-Arg. Here, based on recent research results, we review the metabolic pathways of l-Arg production in E. coli, the research progress of l-Arg production in E. coli, and various regulatory strategies implemented in E. coli.

Laparoscopic liver resection for hepatocellular carcinoma complicated with significant portal hypertension: A propensity score-matched survival analysis.

BACKGROUND: Significant portal hypertension (SPH) is a relative contraindication for patients with resectable hepatocellular carcinoma (HCC). However, increasing evidence indicates that liver resection is feasible for HCC patients with SPH. METHODS: HCC patients with cirrhosis who underwent laparoscopic liver resection (LLR) in two centers from January 2013 to April 2018 were included. Surgical and survival outcomes were analyzed to explore potential prognostic factors. Propensity score matching (PSM) analysis was performed to minimize bias. RESULTS: A total of 165 patients were divided into two groups based on the presence (SPH, n = 76) or absence (non-SPH, n = 89) of SPH. Patients in the SPH group had longer operative time, more blood loss, and more advanced TNM stage than patients in the non-SPH group (P < 0.05). However, there were no significant differences in the postoperative 90-day mortality rate (n = 0), overall postoperative complications (47.4% vs. 41.6%, P = 0.455), Clavien-Dindo classification (P = 0.347), conversion to open surgery (9.2% vs. 6.7%, P = 0.557), or length of hospitalization (16 vs. 15 days, P = 0.203) between the SPH and non-SPH groups before PSM. Similar results were obtained after PSM. The 1-, 3-, and 5-year overall survival (OS) and recurrence-free survival rates in the SPH group were not significantly different from those in the non-SPH group both before and after PSM (log-rank P > 0.05). After PSM, alpha-fetoprotein (AFP) ≥ 400 µg/L [hazard ratio (HR) = 4.71, 95% confidence interval (CI): 2.69-8.25], ascites (HR = 2.18, 95% CI: 1.30-3.66), American Society of Anesthesiologists (ASA) classification (III vs. II) (HR = 2.13, 95% CI: 1.11-4.07) and tumor diameter > 5 cm (HR = 3.91, 95% CI: 2.02-7.56) independently predicted worse OS. CONCLUSIONS: LLR for patients with HCC complicated with SPH appears feasible at the price of increasing operative time and blood loss. AFP, ascites, ASA classification and tumor diameter may predict the prognosis of HCC complicated with SPH after LLR.

CT radiomics nomogram for prediction of the Ki-67 index in head and neck squamous cell carcinoma.

OBJECTIVES: To construct and validate a contrast-enhanced computed tomography (CECT)-based radiomics nomogram to predict Ki-67 expression level in head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 217 patients with HNSCC who underwent CECT scans and immunohistochemical examination of their Ki-67 index were enrolled in this study. The patients were divided into a training set (n = 140; Ki-67: ≥ 50% [n = 72] and < 50% [n = 68]) and an external test set (n = 77; Ki-67: ≥ 50% [n = 38] and < 50% [n = 39]). The least absolute shrinkage and selection operator method was used to select key features for a CECT-image-based radiomics signature and a radiomics score (Rad-score) was calculated. A clinical model was established using clinical data and CT findings. The independent clinical factors and Rad-score were then combined to construct a radiomics nomogram. The performance characteristics of the Rad-score, clinical model, and nomogram were assessed using ROCs and decision curve analysis. RESULTS: Twenty features were finally selected to construct the Rad-score. The radiomics nomogram incorporating the Rad-score, low histological grade, and lymphatic spread showed higher predictive value for the Ki-67 index (≥ 50% vs. < 50%) than the clinical model on both the training (AUC, 0.919 vs. 0.648, p < 0.001) and test (AUC, 0.832 vs. 0.685, p = 0.030) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model. CONCLUSIONS: A CECT-based radiomics nomogram was constructed to predict the expression of Ki-67 in HNSCC. This model showed favorable predictive efficacy and might be useful for prognostic evaluation and clinical decision-making in patients with HNSCC. KEY POINTS: • Accurate pre-treatment prediction of Ki-67 index in HNSCC is crucial. • A CECT-based radiomics nomogram showed favorable predictive efficacy in estimation of Ki-67 expression status in HNSCC patients.

Chloroplast proteostasis: A story of birth, life, and death.

Protein homeostasis (proteostasis) is a dynamic balance of protein synthesis and degradation. Because of the endosymbiotic origin of chloroplasts and the massive transfer of their genetic information to the nucleus of the host cell, many protein complexes in the chloroplasts are constituted from subunits encoded by both genomes. Hence, the proper function of chloroplasts relies on the coordinated expression of chloroplast- and nucleus-encoded genes. The biogenesis and maintenance of chloroplast proteostasis are dependent on synthesis of chloroplast-encoded proteins, import of nucleus-encoded chloroplast proteins from the cytosol, and clearance of damaged or otherwise undesired "old" proteins. This review focuses on the regulation of chloroplast proteostasis, its interaction with proteostasis of the cytosol, and its retrograde control over nuclear gene expression. We also discuss significant issues and perspectives for future studies and potential applications for improving the photosynthetic performance and stress tolerance of crops.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Research progress of Gasdermin D / 中国药理学通报

Pyroptosis is a novel process of programmed inflammatory necrosis, which is closely related to microbial infections and autoimmune diseases. In recent years it has been proved that Gasdermin D is an executive protein of pyroptosis. Cleaved Gasdermin D leads to the formation of pores in cell membrane to induce pyroptosis, and the release of inflammatory factors such as IL-1β and IL-18 aggravates the occurrence of inflammatory responses. With the deepening of Gasdermin D research, it is gradually clear its protein structure and activation sites, which has other activation pathways apart from inducing inflammasome activation. Activation of Gasdermin D does not necessarily mean cell death, even if it could induce the formation of pores in cell membrane and regulation of inflammatory cytokine secretion. These findings offer insight into Gasdermin D function and change our understanding of pyroptosis and programmed necrosis. The recent progress of Gasdermin D is highlighted in this review.

Serum lipoprotein-associated phospholipase A2 level is positively correlated with the recurrence risk of acute ischemic cerebral infarction in hypertensive patients / 南方医科大学学报

OBJECTIVE@#To explore the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and the risk of acute ischemic stroke (AIS) recurrence in hypertensive patients.@*METHODS@#This retrospective case-control study was conducted among 211 hypertensive patients with AIS treated in Foshan First People's Hospital, including 35 patients with recurrence of AIS during the 1-year follow-up as confirmed by head CT/MR. In the overall patients, 60 had grade 1 hypertension (including 5 recurrent cases), 76 had grade 2 hypertension (with 11 recurrent cases), and 75 had grade 3 hypertension (with 19 recurrent cases). Univariate analysis, multivariate logistic regression analysis, trend analysis, and smooth curve fitting analysis were performed to explore the correlation between serum Lp-PLA2 level within 24 h after admission and the risk of AIS recurrence. The predictive efficacy of serum Lp-PLA2 level for AIS recurrence in different hypertension grades was evaluated using ROC curve analysis.@*RESULTS@#Serum Lp-PLA2 level, age, NIHSS score at admission, mRS scores at 7 days, homocysteine level and smoking status differed significantly between patients with and without AIS recurrence (P < 0.05). After adjustment for confounding factors, multivariate regression analysis showed that the highest tertile of Lp-PLA2 level was associated with a 4.13-fold increase of AIS recurrence risk compared with the lowest tertile (OR=5.13, 95% CI: 1.35-19.40), and each 1 ng/mL increase of Lp-PLA2 level was associated with a 1% increase of AIS recurrence risk (OR= 1.01, 95% CI: 1.01-1.02). Serum Lp-PLA2 level was shown to positively correlate with AIS recurrence risk, and in patients with grade 3 hypertension, its areas under the ROC curve for predicting AIS recurrence was 0.869 with a specificity of 0.893 and a sensitivity of 0.737.@*CONCLUSION@#Serum Lp-PLA2 concentration is an independent risk factor and potentially an effective predictor for AIS recurrence in patients with grade 3 hypertension.

Associations of sex hormone levels with body mass index (BMI) in men: a cross-sectional study using quantile regression analysis / 亚洲男科学杂志(英文版)

Body mass index (BMI) has been increasing globally in recent decades. Previous studies reported that BMI was associated with sex hormone levels, but the results were generated via linear regression or logistic regression, which would lose part of information. Quantile regression analysis can maximize the use of variable information. Our study compared the associations among different regression models. The participants were recruited from the Center of Reproductive Medicine, The First Hospital of Jilin University (Changchun, China) between June 2018 and June 2019. We used linear, logistic, and quantile regression models to calculate the associations between sex hormone levels and BMI. In total, 448 men were included in this study. The average BMI was 25.7 (standard deviation [s.d.]: 3.7) kg m-2; 29.7% (n = 133) of the participants were normal weight, 45.3% (n = 203) of the participants were overweight, and 23.4% (n = 105) of the participants were obese. The levels of testosterone and estradiol significantly differed among BMI groups (all P < 0.05). In linear regression and logistic regression, BMI was associated with testosterone and estradiol levels (both P < 0.05). In quantile regression, BMI was negatively associated with testosterone levels in all quantiles after adjustment for age (all P < 0.05). BMI was positively associated with estradiol levels in most quantiles (≤80th) after adjustment for age (all P < 0.05). Our study suggested that BMI was one of the influencing factors of testosterone and estradiol. Of note, the quantile regression showed that BMI was associated with estradiol only up to the 80th percentile of estradiol.

Relationship between nutrient-related dietary pattern and mild cognitive impairment in middle-aged and elderly people in 15 provinces of China / 中华流行病学杂志

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.

The research of liver-targeted drugs based on asialoglycoprotein receptor / 药学学报

Asialoglycoprotein receptor (ASGPR) is highly expressed on the surface of parenchymal liver cells. It can specifically recognize and bind to desialylated glycoproteins which contain terminal galactose or N-acetylgalactosamine residues, and endocytosed by clathrin-mediated endocytosis, transported and then degraded in lysosome. Based on this character, ASGPR mediated liver-targeted drug delivery is likely to increase drug distribution, reduce potential side effects and lower dose. This article reviewed the expression, structure, ligand binding and endocytosis of ASGPR, and summarized the design and optimization of ASGPR ligands and the release strategies. Finally, we put forward some expects about the clinical drug development for ASGPR.

Independent prognostic value of the congestion and renal index in patients with acute heart failure / 老年心脏病学杂志（英文版）

BACKGROUND@#Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF.@*METHODS@#We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes.@*RESULTS@#A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system.@*CONCLUSIONS@#In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.