Research progress on hereditary endocrine and metabolic diseases associated with sensorineural hearing loss / 临床耳鼻咽喉头颈外科杂志

Hereditary endocrine and metabolic diseases , caused by genetic factors, exhibit complex and diverse symptoms, including the possibility of concurrent sensorineural deafness. Currently, there is a limited clinical understanding of hereditary endocrine and metabolic diseases that manifest with deafness, the pathogenesis remains unclear,and there is a lack of effective diagnostic and treatment methods. This article summarizes the research progress of hereditary endocrine and metabolic diseases complicated with deafness from the pathogenesis, clinical phenotype, diagnosis and treatment. Understanding the current research progress and integrating genetic analysis into clinical practice are crucial for accurate diagnosis and treatment, evaluating clinical efficacy, and providing effective genetic counseling for these diseases.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Efectos del ciclismo en la composición corporal e indicadores de riesgo metabólico / Effects of cycling on Body Composition and Metabolic Risk Indicators

Introducción: El ciclismo es una actividad física que se practica de forma recreativa y como actividad laboral, en base a esto los beneficios en la salud varían. Sus efectos pueden extenderse en la regulación de la expresión de citocinas proinflamatorias en la obesidad; sin embargo, se deben estudiar detalles en los indicadores clínicos asociados a otras enfermedades crónico-degenerativas. Objetivo: Identificar los cambios en los parámetros clínicos que sirven como indicadores de riesgo metabólico en personas que realizan ciclismo como ejercicio habitual y como actividad laboral. Métodos: Se realizó una investigación de diseño transversal, descriptivo en el Estado de México, México. Se formaron 3 grupos de 16 participantes provenientes de Toluca y municipios aledaños. Se realizaron mediciones de composición corporal y análisis bioquímicos para identificar las diferencias entre los grupos a través de la prueba t- student y el análisis de varianza ANOVA. Resultados: Los análisis estadísticos reportaron diferencias significativas en las concentraciones de lipoproteínas de alta densindad y triglicéridos. Para el grupo de los conductores de bicitaxi fue más favorable, se detalla como el tiempo de la actividad ayuda a mantener los parámetros de composición corporal como el porcentaje del tejido muscular y adiposo. Conclusiones: Los beneficios del ciclismo se presentaron con diferentes grados de eficiencia de acuerdo con la modalidad en la que se practican. Las variables no cambian de forma significativa en ningún grupo, pueden ser dependientes de otras variables como la alimentación(AU)

Introduction: Cycling is a physical activity, which is practiced recreationally and as a work activity. Its effects may extend to the regulation of the expression of proinflammatory cytokines in obesity; however, details should be studied in the clinical indicators associated with other chronic-degenerative diseases. Objective: To identify changes in clinical parameters that serve as indicators of metabolic risk in people who perform cycling as a regular exercise and as a work activity. Methods: A cross-sectional and descriptive design research was carried out in the State of Mexico, Mexico. Three groups of 16 participants were formed from Toluca and surrounding municipalities. Body composition measurements and biochemical analyzes were performed to identify differences between groups through Student's t test and ANOVA analysis of variance. Results: Statistical analyzes reported significant differences in HDL and triglyceride concentrations. For the group of pedicab drivers it was more favorable, it is detailed how the time of the activity helps to maintain body composition parameters such as the percentage of muscle and adipose tissue. Conclusions: The benefits of cycling were presented with different degrees of efficiency according to the modality in which they are practiced. The variables do not change significantly in any group and may be dependent on other variables such as diet(AU)

Comparación entre la morbilidad y la mortalidad por COVID-19, asociada a factores de riesgo metabólicos en población no indígena e indígena de México / Comparison between morbidity and mortality from COVID-19, associated with metabolic risk factors in non-indigenous and indigenous populations of Mexico

Introducción. La investigación sobre la pandemia de COVID-19, se ha estudiado en tiempo real, ha sido y sigue siendo reveladora. Objetivo. Analizar la morbilidad y la mortalidad por COVID-19, asociadas a factores de riesgo metabólicos en población no indígena e indígena de México. Materiales y métodos. Utilizamos la Base Nacional de Datos COVID-19, durante los años críticos 2020-2021- 2022. Se trabajó con 5.380.247 casos que representaron la población total de positivos al SARS-CoV-2. Se analizaron las discrepancias entre las prevalencias de población no indígena, población indígena, defunción y no defunción. Se definió población indígena, con la clasificación oficial de auto-identificación. Se aplicó el modelo de regresión logística para determinar el riesgo de morir para cada variable: enfermedades cardiovasculares, hipertensión, diabetes, obesidad, sexo, edad y condición indígena. El análisis de multicolinealidad se analizó a través de la prueba de asociación Phi para variables dicotómicas y a través del ajuste de Nagelkerke. Resultados. En los positivos totales 99,2% fue población no indígena y 0,8% indígenas, mientras su porcentaje de letalidad fue de 5,8% y 11,1% respectivamente. En ambos grupos, murieron más hombres (61,5%) que mujeres (38,5%) y las edades de mayor defunción fueron 60 a 79 años. La mortalidad por enfermedades cardiovasculares fue la de mayor incidencia, 26,6% en población general y 32,3% en indígena; por diabetes 22,1% y 27,9%; hipertensión 20,0% y 26,7%y la obesidad 11, 3% y 17,4% respectivamente. Los análisis de regresión logística se ajustaron por sexo, edad y condición indígena. El condicionante de mayor riesgo de muerte, fueron las comorbilidades metabólicas y el de menor riesgo, la condición indígena. Conclusiones. El impacto de la pandemia por COVID-19 fue más grave cuando hubo padecimientos metabólicos tanto en la población no indígena como en la indígena(AU)

Introduction. Research on the COVID-19 pandemic, studied in real time, has been and continues to be revealing. Objective. To analyze morbidity and mortality from COVID-19, associated with metabolic risk factors in non-indigenous and indigenous populations of Mexico. Materials and methods. We use the National COVID-19 Database, during the critical years 2020-2021-2022. We worked with 5,380,247 cases that represented the total population of SARS-CoV-2 positives. The discrepancies between the prevalence of non-indigenous population, indigenous population, death and non-death were analyzed. The indigenous population was defined, with the official self-identification classification. The logistic regression model was applied to determine the risk of dying for each variable: cardiovascular diseases, hypertension, diabetes, obesity, sex, age and indigenous status. The multicollinearity analysis was analyzed through the Phi association test for dichotomous variables and through the Nagelkerke adjustment. Results. Of the total positives, 99.2% were non-indigenous people and 0.8% were indigenous, while their fatality percentage was 5.8% and 11.1% respectively. In both groups, more men (61.5%) than women (38.5%) died and the ages of greatest death were 60 to 79 years. Mortality from cardiovascular diseases was the one with the highest incidence, 26.6% in the general population and 32.3% in the indigenous population; due to diabetes 22.1% and 27.9%; hypertension 20.0% and 26.7% and obesity 11.3% and 17.4% respectively. Logistic regression analyzes were adjusted for sex, age, and indigenous status. The condition with the highest risk of death was metabolic comorbidities and the lowest risk was indigenous status. Conclusions. The impact of the COVID-19 pandemic was more serious when there were metabolic disorders in both the non-indigenous and indigenous populations(AU)

Cirugía bariátrica y evolución de COVID-19 / Bariatric surgery and evolution of COVID-19

INTRODUCTION. Obesity is recognized as a risk factor for developing severe new coronavirus disease. Bariatric surgery prior to infection could behave as a protective factor against serious infections and death. OBJECTIVE. To describe the impact of bariatric surgery on the severity and mortality of patients with obesity and new coronavirus disease; through a systematic review and meta-analysis of the specialized literature from 2020-2022. METHODOLOGY. Publications indexed in databases such as Pubmed, Tripdatabase, and Google scholar, on the impact of previous bariatric surgery on the evolution and prognosis of patients with new coronavirus disease were taken. The Newcastle-Ottawa scale was used to assess quality and risk of bias. RevMan 5.0 software was used for statistical analysis. RESULTS. Eight cohort studies were included, with a population of 137 620 adult subjects with obesity and new coronavirus disease; of these, 5638 (4.09%) had a history of bariatric surgery. In the meta-analysis, it was determined that, in subjects with obesity and new coronavirus disease, the history of bariatric surgery had a protective effect against the use of mechanical ventilation [OR: 0.68; 95% CI: 0.62-0.75] (p<0.001) and mortality [OR: 0.57; 95% CI: 0.50-0.65] (p<0.01). CONCLUSIONS. The history of bariatric surgery in subjects with obesity seems to have a protective effect against the severity defined by the use of mechanical ventilation in patients with obesity and mortality due to the new coronvirus disease; therefore, the resumption of bariatric surgical activity, at pre-pandemic levels, could represent an additional benefit for candidate subjects.

INTRODUCTION. Obesity is recognized as a risk factor for developing severe new coronavirus disease. Bariatric surgery prior to infection could behave as a protective factor against serious infections and death. OBJECTIVE. To describe the impact of bariatric surgery on the severity and mortality of patients with obesity and new coronavirus disease; through a systematic review and meta-analysis of the specialized literature from 2020-2022. METHODOLOGY. Publications indexed in databases such as Pubmed, Tripdatabase, and Google scholar, on the impact of previous bariatric surgery on the evolution and prognosis of patients with new coronavirus disease were taken. The Newcastle-Ottawa scale was used to assess quality and risk of bias. RevMan 5.0 software was used for statistical analysis. RESULTS. Eight cohort studies were included, with a population of 137 620 adult subjects with obesity and new coronavirus disease; of these, 5638 (4.09%) had a history of bariatric surgery. In the meta-analysis, it was determined that, in subjects with obesity and new coronavirus disease, the history of bariatric surgery had a protective effect against the use of mechanical ventilation [OR: 0.68; 95% CI: 0.62-0.75] (p<0.001) and mortality [OR: 0.57; 95% CI: 0.50-0.65] (p<0.01). CONCLUSIONS. The history of bariatric surgery in subjects with obesity seems to have a protective effect against the severity defined by the use of mechanical ventilation in patients with obesity and mortality due to the new coronvirus disease; therefore, the resumption of bariatric surgical activity, at pre-pandemic levels, could represent an additional benefit for candidate subjects.

Application of live biotherapeutic products and perspective in the treatment of inherited metabolic disease / 生物工程学报

Live biotherapeutic products (LBPs) refer to the living bacteria derived from human body intestinal gut or in nature that can be used to treat the human disease. However, the naturally screened living bacteria have some disadvantages, such as deficient therapeutic effect and great divergence, which fall short of the personalized diagnosis and treatment needs. In recent years, with the development of synthetic biology, researchers have designed and constructed several engineered strains that can respond to external complex environmental signals, which speeded up the process of development and application of LBPs. Recombinant LBPs modified by gene editing can have therapeutic effect on specific diseases. Inherited metabolic disease is a type of disease that causes a series of clinical symptoms due to the genetic defect of some enzymes in the body, which may cause abnormal metabolism the corresponding metabolites. Therefore, the use of synthetic biology to design LBPs targeting specific defective enzymes will be promising for the treatment of inherited metabolic defects in the future. This review summarizes the clinic applications of LBPs and its potential for the treatment of inherited metabolic defects.

Research progress on the role and clinical significance of DNA methylation in early nutritional programming / 生理学报

Early life nutritional environment is not only associated with the growth and development of children, but also affects the health of adults. Numerous epidemiological and animal studies suggest that early nutritional programming is an important physiological and pathological mechanism. DNA methylation is one of the important mechanisms of nutritional programming, which is catalyzed by DNA methyltransferase, a specific base of DNA covalently binds to a methyl group, to regulate gene expression. In this review, we summarize the role of DNA methylation in the "abnormal developmental planning" of key metabolic organs caused by excessive nutrition in early life, resulting in long-term obesity and metabolic disorders in the offspring, and explore the clinical significance of regulating DNA methylation levels through dietary interventions to prevent or reverse the occurrence of metabolic disorders in the early stage in a "deprogramming" manner.

Hyperoxia caused intestinal metabolism disorder in mice / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of hyperoxia on intestinal metabolomics in mice.@*METHODS@#Sixteen 8-week-old male C57BL/6 mice were randomly divided into hyperoxia group and control group, with 8 mice in each group. The hyperoxia group was exposed to 80% oxygen for 14 days. Mice were anesthetized and euthanized, and cecal contents were collected for untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) combined detection. Orthogonal partial least square discriminant analysis (OPLS-DA), volcano plot analysis, heat map analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the effects of hyperoxia on metabolism.@*RESULTS@#(1) OPLS-DA analysis showed that R2Y was 0.967 and Q2 was 0.796, indicating that the model was reliable. (2) Volcano plot and heat map analysis showed significant statistical differences in the expression levels of metabolites between the two groups, with 541 up-regulated metabolites, 64 down-regulated metabolites, and 907 no differences, while the elevated 5-hydroxy-L-lysine was the most significant differential metabolite induced by high oxygen. (3) KEGG pathway enrichment analysis showed that porphyrin and chlorophyll metabolism (P = 0.005), lysine degradation (P = 0.047), and aromatic compound degradation (P = 0.024) were the targets affected by hyperoxia. (4) Differential analysis of metabolic products through KEGG enrichment pathway showed that hyperoxia had a significant impact on the metabolism of porphyrin and chlorophyll, lysine, and aromatic compounds such as benzene and o-cresol.@*CONCLUSIONS@#Hyperoxia significantly induces intestinal metabolic disorders. Hyperoxia enhances the metabolism of porphyrins and chlorophyll, inhibits the degradation of lysine, and delays the degradation of aromatic compounds such as benzene and o-cresol.

Micropeptides: origins, identification, and potential role in metabolism-related diseases / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.

A descriptive analysis of hyperlipidemia in adult twins in China / 中华流行病学杂志

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.

Advances in research on the clinical phenotype and genetic etiology of jaundice associated with Hereditary bilirubin metabolic disorders / 中华医学遗传学杂志

Hereditary bilirubin metabolic disorder is an important cause for jaundice. For its diverse types and similar clinical manifestations, it has been difficult to make a clear etiological diagnosis. The application of next generation sequencing in recent years has delineated the more and more genetic etiologies for jaundice. This article has reviewed the clinical manifestations and genetic etiology of bilirubin metabolic disorder jaundice, with an aim to enhance the understanding of such diseases and facilitate their clinical diagnosis and treatment, which will provide a reference for genetic counseling and/or prenatal diagnosis for the affected individuals and families.

Research progress of the regulatory role of autophagy in metabolic liver diseases / 中华肝脏病杂志

Autophagy is one of several hepatic metabolic processes in which starved cells are supplied with glucose, free fatty acids, and amino acids to produce energy and synthesize new macromolecules. Moreover, it regulates the quantity and quality of mitochondria and other organelles. As the liver is a vital metabolic organ, specific forms of autophagy are necessary for maintaining liver homeostasis. Protein, fat, and sugar are the three primary nutrients that can be altered by different metabolic liver diseases. Drugs that have an effect on autophagy can either promote or inhibit autophagy, and as a result, it can either increase or inhibit the three major nutritional metabolisms that are affected by liver disease. Thus, this opens up a novel therapeutic option for liver disease.

Tendencia de consejerías en actividad física y enfermedades cardiometabólicas en el Maule, Chile: estudio previo a pandemia por COVID-19 entre 2012 y 2019 / Trend in Physical Activity Counseling and Cardiometabolic Diseases in Maule, Chile: COVID-19 Pre-Pandemic Study between 2012 and 2019

BACKGROUND: Physical activity (PA) practice reduces the adverse effects of COVID-19. PA counseling promotes healthy lifestyles and prevents cardiometabolic diseases. AIM: To assess the trend in cases of PA counseling and the cardiometabolic disease between 2012 and 2019 (before COVID-19) in a southern Chilean region. MATERIAL AND METHODS: Records of Maule Region Health Service for 731.163 men, and 829.097 women aged < 10 to ≥ 65 years were analyzed. The average annual percentage change (AAPC) during the study period and the annual percentage change (APC) during intermediate periods, were calculated. RESULTS: There was a significant decrease in PA counseling in women in the study period (AAPC: −13.6%). In the 2012-2017 period a significant decrease in counseling for total, men and women were observed (APC: −18.1, −16.5 and −19.1%, respectively). Obesity increased significantly in total, men and women in the 2012-2019 period (AAPC: 10.1, 8.5 and 10.7%, respectively). The same trend was observed for hypertension (AAPC: 8.1, 8.5 and 7.6% respectively) and elevated blood glucose (AAPC: 10, 11.5 and 9.6%, respectively). CONCLUSIONS: In the study period PA counseling decreased along with an increase in obesity, hypertension and high blood glucose. Increasing PA counseling is a mainstay in the prevention of cardiometabolic diseases and probably to prevent contagion and complement the treatment of COVID-19.

Activación de sensores del estrés del retículo endoplásmico por dietas asociadas a enfermedades metabólicas y COVID-19 / Activation of endoplasmic reticulum stress sensors by metabolic disease-associated diets and COVID-19

El retículo endoplásmico es un organelo abundante, dinámico y sensor de energía. Sus abundantes membranas, rugosa y lisa, se encuentran distribuidas en diferentes proporciones dependiendo del linaje y requerimiento celular. Su función es llevar a cabo la síntesis de proteínas y lípidos, y es el almacén principal de Ca2+ intracelular. La sobrecarga calórica y la glucolipotoxicidad generada por dietas hipercalóricas provoca la alteración del retículo endoplásmico, activando la respuesta a proteínas mal plegadas (UPR, Unfolded Protein Response, por sus siglas en inglés) como reacción al estrés celular relacionado con el retículo endoplásmico y cuyo objetivo es restablecer la homeostasis del organelo al disminuir el estrés oxidante, la síntesis de proteínas y la fuga de Ca2+. Sin embargo, durante un estrés crónico, la UPR induce formación de especies reactivas de oxígeno, inflamación y apoptosis, exacerbando el estado del retículo endoplásmico y propagando un efecto nocivo para los demás organelos. Es por ello que el estrés del retículo endoplásmico se ha considerado un inductor del inicio y desarrollo de enfermedades metabólicas, incluido el agravamiento de COVID-19. Hasta el momento, existen pocas estrategias para reestablecer la homeostasis del retículo endoplásmico, las cuales son dirigidas a los sensores que desencadenan la UPR. Por tanto, se justifica con urgencia la identificación de nuevos mecanismos y terapias novedosas relacionadas con mitigar el impacto del estrés del retículo endoplásmico y las complicaciones asociadas.

The endoplasmic reticulum is an abundant, dynamic and energy-sensing organelle. Its abundant membranes, rough and smooth, are distributed in different proportions depending on the cell lineage and requirement. Its function is to carry out protein and lipid synthesis, and it is the main intracellular Ca2+ store. Caloric overload and glycolipotoxicity generated by hypercaloric diets cause alteration of the endoplasmic reticulum, activating the Unfolded Protein Response (UPR) as a reaction to cellular stress related to the endoplasmic reticulum and whose objective is to restore the homeostasis of the organelle by decreasing oxidative stress, protein synthesis and Ca2+ leakage. However, during chronic stress, the UPR induces reactive oxygen species formation, inflammation and apoptosis, exacerbating the state of the endoplasmic reticulum and propagating a deleterious effect on the other organelles. This is why endoplasmic reticulum stress has been considered an inducer of the onset and development of metabolic diseases, including the aggravation of COVID-19. So far, few strategies exist to reestablish endoplasmic reticulum homeostasis, which are targeted to sensors that trigger UPR. Therefore, the identif ication of new mechanisms and novel therapies related to mitigating the impact of endoplasmic reticulum stress and associated complications is urgently warranted.

Mechanisms of Dangua Recipe in Improving Glycolipid Metabolic Disorders Based on Transcriptomics / 中国结合医学杂志

OBJECTIVE@#To explore the mechanisms of Dangua Recipe (DGR) in improving glycolipid metabolism based on transcriptomics.@*METHODS@#Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table, including a conventional diet group (Group A), a DGR group (Group B, high-calorie diet + 20.5 g DGR), and a high-calorie fodder model group (Group C). After 12 weeks of intervention, the liver tissue of rats was taken. Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy, and then gene or protein validation of liver tissue were performed. Nicotinamide phosphoribosyl transferase (Nampt) and phosphoenolpyruvate carboxykinase (PEPCK) proteins in liver tissues were detected by enzyme linked immunosorbent assay, fatty acid synthase (FASN) protein was detected by Western blot, and fatty acid binding protein 5 (FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction. Furthermore, the functional verification was performed on the diabetic model rats by Nampt blocker (GEN-617) injected in vivo. Hemoglobin A@*RESULTS@#Totally, 257 differential-dominant genes of Group A vs. Group C and 392 differential-dominant genes of Group B vs. Group C were found. Moreover, 11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs. Group C and Group C vs. Group B were confirmed. The liver tissue target validation showed that Nampt, FASN, PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome. The in vivo functional tests showed that GEN-617 increased body weight, HbA@*CONCLUSION@#Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.

Clinicopathological features of hepatic fibrinogen storage disease in children / 中华病理学杂志

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.

Research progress on the relationship between HIV infection, antiretroviral therapy, and diabetes mellitus / 中华流行病学杂志

The expectancy and quality of life among people with HIV have improved remarkably with the widespread use of antiretroviral therapy (ART). In the meantime, the risks for HIV-related metabolic diseases have increased significantly, in particular diabetes mellitus. Multi-factors coeffect to increasing the risk of diabetes mellitus among HIV patients. Recently, growing of research has reported an association between HIV infections and ART and the development of diabetes mellitus. In this article, we summarize the recent studies investigating HIV infection and ART in diabetes mellitus to clarify their mechanism on the development of diabetes.

Pre-conception carrier screening for 21 inherited metabolic diseases in a Chinese population / 中华医学遗传学杂志

OBJECTIVE@#To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age.@*METHODS@#A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed.@*RESULTS@#One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria.@*CONCLUSION@#This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.

Joint Association of Metabolic Health and Obesity with Ten-Year Risk of Cardiovascular Disease among Chinese Adults / 生物医学与环境科学（英文）

OBJECTIVE@#This study aims to investigate the association of metabolic phenotypes that are jointly determined by body mass index (BMI) or fat mass percentage and metabolic health status with the ten-year risk of cardiovascular disease (CVD) among Chinese adults.@*METHODS@#Data were obtained from a cross-sectional study. BMI and body fat mass percentage (FMP) combined with the metabolic status were used to define metabolic phenotypes. Multiple linear regression and logistic regression were used to examine the effects of metabolic phenotypes on CVD risk.@*RESULTS@#A total of 13,239 adults aged 34-75 years were included in this study. Compared with the metabolically healthy non-obese (MHNO) phenotype, the metabolically unhealthy non-obese (MUNO) and metabolically unhealthy obese (MUO) phenotypes defined by BMI showed a higher CVD risk [odds ratio, OR (95% confidence interval, CI): 2.34 (1.89-2.89), 3.45 (2.50-4.75), respectively], after adjusting for the covariates. The MUNO and MUO phenotypes defined by FMP showed a higher CVD risk [ OR (95% CI): 2.31 (1.85-2.88), 2.63 (1.98-3.48), respectively] than the MHNO phenotype. The metabolically healthy obese phenotype, regardless of being defined by BMI or FMP, showed no CVD risk compared with the MHNO phenotype.@*CONCLUSION@#General obesity without central obesity does not increase CVD risk in metabolically healthy individuals. FMP might be a more meaningful factor for the evaluation of the association of obesity with CVD risk. Obesity and metabolic status have a synergistic effect on CVD risk.

Exercise regulates lipid metabolism via lipophagy and its molecular mechanisms / 生理学报

Lipophagy is a kind of selective autophagy, which can selectively identify and degrade lipid droplets and plays an important role in regulating cellular lipid metabolism and maintaining intracellular lipid homeostasis. Exercise can induce lipophagy and it is also an effective means of reducing body fat. In this review, we summarized the relationship between exercise and lipophagy in the liver, pancreas, adipose tissue, and the possible molecular mechanisms to provide a new clue for the prevention and treatment of fatty liver, obesity and other related metabolic diseases by exercise.