Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai

Objective This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease(CKD)in Shanghai community residents.Methods We used data from a cohort study of community residents who participated in three examinations in 2008,2009,and 2013,respectively.Fasting plasma glucose(FPG)level,blood pressure(BP),and lipid levels were determined in 2,109 participants at all three visits,and CKD was evaluated between the second and the third visits.Visit-to-visit variabilities in metabolic factors were described by coefficients of variation(CV)at three visits.A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV.CKD was defined as the estimated glomerular filtration rate<60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio≥30 mg/g.Results A total of 200(9.5%)participants had CKD at the third visit.Compared with the lowest quartile of CV,the highest quartile was associated with a 70%increased risk of CKD for FPG[odds ratio,OR=1.70;95%confidence interval(CI)1.06–2.72],62%for systolic BP(OR=1.62,95%CI 1.04–2.50),and 85%for low-density lipoprotein cholesterol(OR=1.85,95%CI 1.23–2.80).Furthermore,the risk of CKD increased significantly with an increasing variability score.Compared with participants with score 0,participants with scores of 1,2,and 3 were associated with 58%(OR=1.58,95%CI 1.08–2.32),121%(OR=2.21,95%CI 1.40–3.49),and 548%(OR=6.48,95%CI 3.18–13.21)higher risks of CKD,respectively.Conclusion The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.

Could Metabolic Risk Factors Affect the Severity of Knee Osteoarthritis in Type-2 Diabetes Mellitus Patients? A Cross-Sectional Study

Introduction: Osteoarthritis (OA) is a common joint disease with varying degrees of severity. Patients with type-2 diabetes mellitus (T2DM) demonstrate a higher prevalence of OA, and several mechanisms have been proposed to explain the severity of OA in DM. In this study, we aimed to explore the effect of metabolic risk factors on the severity of knee OA in T2DM patients. Methods: This cross-sectional study was conducted in 2018 and included 57 patients with T2DM. Data were collected in terms of demographic variables and metabolic tests. After obtaining a medical history and examination, anteroposterior (AP) and lateral radiographs of both knees were taken, and the severity of OA was classified using the Kellgren-Lawrence (KL) classification system and categorized into two groups. Group A demonstrated patients with mild OA equivalent to grade 1 or 2 KL and group B showed moderate to severe OA (grade 3 or 4 KL). Results: A total of 57 patients with T2DM enrolled in the study, of which 32 patients exhibited grade 1 or 2 KL (group A) and 25 with grade 3 or 4 KL (group B). The mean age and mean body mass index (BMI) were higher in group B compared to group A, and the differences were statistically significant (P-value = 0.01). As with the other metabolic tests, the mean serum hemoglobin A1C (HbA1c) level was not statistically significant (P-value = 0.34). Conclusion: The data revealed that metabolic factors play a minor role in the severity of OA in patients with DM and that these changes are primarily influenced by increasing BMI and age.

From metabolic dysfunction-associated fatty liver disease to metabolic dysfunction-associated steatotic liver disease:Controversy and consensus

The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease(MASLD)in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns.This marks the second instance of significant renaming of non-alcoholic fatty liver disease since the introduction of metabolic dysfunction-associated fatty liver disease(MAFLD)in 2020.The nomenclature and definitions of MASLD and MAFLD exhibit significant disparities as well as substantial consensus.The disparities regarding the framework of nomenclature,the definitions,the clinical management,and the impact on the clinical outcomes between MASLD and MAFLD were comprehensively compared in this editorial.Additionally,the consensus reached by the MASLD and MAFLD definitions also emphasizes positive diagnosis rather than negative diagnosis within the framework of establishing a diagnostic approach.Furthermore,they acknowledged the pivotal role of metabolic dysfunction in the pathogenesis of MAFLD or MASLD and the positive role of increasing the awareness of the disease in public.Fortunately,the non-invasive tests remains effective in the MASLD and MAFLD era.Elucidating these disparities would contribute to a more comprehensive comprehension of the nature of steatotic liver disease and enhance clinical practice.Thus,more efforts are required to reach more consensus about these important topics.

Metabolic aspects of hepatitis C virus

Many metabolic factors are associated with chronic hepatitis C virus(HCV)infection and can influence the course of the illness and impact the progression of liver and non-liver-related diseases through complex interactions.Several of these factors impact the course of chronic HCV(CHC)and result in the conceptual translation of CHC from a localized to systemic disease.Besides the traditional liver manifestations associated with CHC infection,such as cirrhosis and hepatocellular carcinoma,various extrahepatic disorders are associated with HCV infection,including atherosclerosis,glucose and lipid metabolic disturbances,alterations in the iron metabolic pathways,and lymphoproliferative diseases.The coexistence of metabolic disorders and CHC is known to influence the chronicity and virulence of HCV and accelerates the progression to liver fibrosis and hepatocellular carcinoma.Insulin resistance is one of the key factors that have a tremendous metabolic impact on CHC.Therefore,there is a great need to properly evaluate patients with CHC infection and correct the modifiable metabolic risk factors.Furthermore,patients with HCV who achieved a sustained virological response showed an overall improvement in glucose metabolism,but the exact evidence still requires further studies with long-term follow-up.This review delineates the most recent evidence on the main metabolic factors associated with CHC and the possible influence of chronic HCV infection on metabolic features.

Comparative Study of Inflammatory and Oxidative Stress Biomarkers in Different Metabolically Healthy Obesity Phenotypes

Aims: Obesity is the major contributor of the metabolic syndrome (MetS), but a unique phenotype of obesity known as metabolically healthy obese (MHO) shows healthier metabolic profile; however understanding of their biochemical correlates is poorly understood. Obesity is defined by Body mass index (BMI), but controversy exists regarding ethnic-specific BMI cut-offs. The present study used the Asian Indian BMI cut-offs to assess relationships of MHO phenotypes with oxidative stress (OS) and inflammation. Methods: In this case-control study, 299 metabolically-healthy (MH) respondents were divided into four groups as per Asian criteria for obesity: MH non-obese (MHNO), MH overweight (MHOW), MHO and MH severely obese (MHSO). Their oxidative stress and pro-inflammatory markers were measured. Results: Levels of hydroxyl radicals (·OH), fluorescent oxidation products (FLOP), MDA, PCO and inflammatory markers CRP, TNF-α, IL-6 were highest in MHSO phenotype followed by the MHO, MHOW and MHNO groups (p > 0.0001), whereas antioxidant markers, CuZn-SOD, catalase, glutathione peroxidase and total antioxidant activity followed the reverse trend. The MHNO and MHOW groups showed significant difference with regard to (·OH) radicals and FLOP. Moreover, ·OH radicals, FLOP and inflammatory markers were significantly correlated to BMI in MHSO and MHO but not in MHNO and MHOW group. Conclusion: The MHO and MHSO phenotype display differences in terms of OS and inflammatory markers at lower BMI cut-offs, indicating that they may be on the way to becoming “unhealthy” obese. The lower BMI cut-offs proposed by Indian Consensus Group would help in understanding of manifestation of metabolic syndrome.

Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients

BACKGROUND Tenofovir alafenamide(TAF)has a serum lipid-raising effect in patients with HIV;however,its effect on serum lipids and nonalcoholic fatty liver disease(NAFLD)risk in patients with chronic hepatitis B(CHB)is unclear.AIM To compare the effects of TAF and entecavir(ETV)on serum lipid levels in patients with CHB.METHODS In this retrospective cohort study,the data including the clinical features,serum lipids,and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed.We used propensity score-matched models to assess the effects on high-density lipoprotein,lowdensity lipoprotein,triglycerides,and total cholesterol(TCHO).RESULTS A total of 336 patients(75.60%male)were included;63.69%received TAF and 36.31%received ETV.Compared with the ETV group,the TAF group had significantly higher TCHO levels after treatment(4.67±0.90 vs 4.36±1.05,P=0.006).In a propensity score-matched model for body mass index,age,sex,smoking,drinking,presence of comorbidities such as NAFLD,cirrhosis,diabetes mellitus,and hypertension,TAF-treated patients had significantly increased TCHO levels compared to that at baseline(P=0.019).There was no difference for the ETV group.Body mass index,sex,hypertension,baseline TCHO,and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis.However,1-year TAF treatment did not increase the incidence of NAFLD.CONCLUSION A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV.However,TAF-induced dyslipidemia did not increase the incidence of NAFLD.

Mast Cells:The Key to Multiple Sclerosis?

Mast cells are present in high numbers in the border-zones of the multiple sclerosis-plaques. They are located in small clusters along capillaries and venules, and they are more abundant in females than in men. Mast cells can be stimulated to release specific mediators such as histamine, resulting in oedema formation, as well as proteases that may cause demyelination, by several different activation mechanisms. We hypothesize that a putative mast cell activation may be induced by diet factor(s) as well as long lasting mental stress that may lead to the release of catestatin, as well as ACTH released from the pituitary gland. Given a natural flux of mast cell recovery and activation, a putative phenomenon of massive release of mediators and “silent” reload periods may explain the relapsing-remitting phases of multiple sclerosis.

Relationship between tumor necrosis factor-α and liver fibrosis

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Immunohistochemical study on expression of epidermal growth factor receptor at hepatocyte nuclei in experimental rat liver cirrhosis

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Research Progress on Prevention and Treatment of Glucolipid Metabolic Disease with Integrated Traditional Chinese and Western Medicine

Hyperlipidemia, type 2 diabetes mellitus, nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients. In addition, these diseases are closely related in pathophysiological settings. However, increasing of the disease incidence, lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattem of the single disease, single target therapy, that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine （WM）. On the basis of the combination of the advantages of integrated Chinese medicine （CM） and WM, with unified understanding of such diseases, the new concept of glucolipid metabolic disease （GLMD） is introduced. In this new concept, disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD. The key points of pathology included dysfunction of neuronal-endocrine-immune system,insulin resistance, oxidative stress, inflammation and intestinal flora imbalance. In the core pathogenic perspective of CM, it can be explained as ＂Gan （Liver） Shi Shu Xie＂ （dysfunction of Gan in metabolism and emotion regulation） that will lead to the occurence/production of endogenous dampness and phlegm, blood stasis and turbid. This leads to the new concept of ＂Liver-based regulatory system for metabolic homeostasis＂ to be introduced further. The comprehensive prevention and control strategy ＂Tiao Gan Qi Shu Hua Zhuo＂ （modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness）. Its representative formula Fufang Zhenzhu Tiaozhi Capsule （复方贞术调脂胶囊） is innovated under such rationales. Comment for some commonly-used CM GLMD therapeutic drugs was presented. High-level evidence-based and epidemiological and mechanism studies should be carded out to further interpret and explain of the scientific connotation of GLMD.

Factors influencing glucose metabolism in young obese subjects with obstructive sleep apnea hypopnea syndrome

Objective To explore the factors influencing glucose metabolism in young obese subjects with obstructive sleep apnea hypopnea syndrome(OSAHS).Methods A total of 106 young obese subjects[18-44 years old,body mass index(BMI)≥30 kg/m^2]were enrolled and divided into two groups based on full-night polysomnography(PSG),OSAHS group[apnea hypopnea index(AHI)

Polymorphisms of estrogen-metabolizing genes and breast cancer risk: a multigenic study

Background Endogenous estrogen plays a very important role in the carcinogenesis and progression of breast cancer. The enzymes involved in the biosynthesis and metabolism of estrogen have been proposed to contribute to this effect. To examine this hypothesis, we conducted a case-control study to investigate the relationship between polymorphisms of genes responsible for estrogen biosynthesis （CYP17, cytochrome P450c17a and CYP19, aromatase cytochrome P450） and estrogen sulfation of inactivation （ SULT1 A1, sulfotransferasel A1 ） and the risk of breast cancer in Chinese women. Methods This study involved 213 breast cancer patients and 430 matched controls. PCR-based restriction fragment length polymorphism （RFLP） and short tandem repeat polymorphism （STRP） assays were used to detect the mononucleotide transition of CYP17 and SULT1A1 and tandem repeat polymorphism of CYP19. Logistic regression analyses were used to determine OR and 95% CI of each and all three high-risk genotypes, of all three genotypes combined, and of estrogen exposure factbrs. The relationship between each high-risk genotype and clinicalpathological characteristics were also assessed. Results The frequency of A2 allele of CYP17 was 49.8% in cases and 49. 1% in controls （P =0. 82）. The frequency of His allele of SULT1A1 was significantly higher in cases （ 13.6% ） than in controls （9. 5% ） （P 〈 0. 05 ）. There was also significant difference of the （TTTA）10 allele of CYP19 which was 12. 4% in cases and 8.2% in controls （P 〈0. 05）. When the CYP17 A2 allele, CYP19 （TITA）1o and SULT1A1 His allele were considered as the “putative high-risk” genotype, there was an increased risk of breast cancer with the number of high-risk genotypes in a dose-response effect （trend, P = 0. 05 ）. In multivariate analysis, the SULT1A1 genotype remained the most significant determinant for breast cancer, with OR =2. 37 （95% CI 1.23 - 4. 74） , followed by CYP19, with OR = 1.75 （95% CI 1.27 - 3.56）. The （TTTA）10 allele of CYP19 was associated with tumor size, and the His allele of SULT1 A1 associated with status of lymph node metastasis. Conclusions This study supports the hypothesis that breast cancer can be initiated by estrogen exposure and that estrogen metabolizing genes are involved in this mechanism. This multigenic model is useful for identifying individuals who are at higher risks of breast cancer.

Community structure and elevational diversity patterns of soil Acidobacteria

Acidobacteria is one of the most dominant and abundant phyla in soil,and was believed to have a wide range of metabolic and genetic functions. Relatively little is known about its community structure and elevational diversity patterns. We selected four elevation gradients from 1000 to 2800 m with typical vegetation types of the northern slope of Shennongjia Mountain in central China. The vegetation types were evergreen broadleaved forest,deciduous broadleaved forest,coniferous forest and sub-alpine shrubs. We analyzed the soil acidobacterial community composition,elevational patterns and the relationship between Acidobacteria subdivisions and soil enzyme activities by using the 16 S rRNA meta-sequencing technique and multivariate statistical analysis. The result found that 19 known subdivisions as well as an unclassified phylotype were presented in these forest sites,and Subdivision 6 has the highest number of detectable operational taxonomic units（OTUs）. A significant single peak distribution pattern（P 〈 0.05） between the OTU number and the elevation was observed. The Jaccard and Bray–Curtis index analysis showed that the soil Acidobacteria compositional similarity significantly decreased（P 〈 0.01） with the increase in elevation distance. Mantel test analysis showed the most of the soil Acidobacteria subdivisions had the significant relationship（P 〈 0.01） with different soil enzymes. Therefore,soil Acidobacteria may be involved in different ecosystem functions in global elemental cycles. Partial Mantel tests and CCA analysis showed that soil pH,soil temperature and plant diversity may be the key factors in shaping the soil Acidobacterial community structure.