Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

The diagnosis of hematological disorders is currently established from the combined results of different tests, including those assessing morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology (M) (collectively known as the MICM classification). In this workflow, most of the results are interpreted manually (i.e., by a human, without automation), which is expertise-dependent, labor-intensive, time-consuming, and with inherent interobserver variability. Also, with advances in instruments and technologies, the data is gaining higher dimensionality and throughput, making additional challenges for manual analysis. Recently, artificial intelligence (AI) has emerged as a promising tool in clinical hematology to ensure timely diagnosis, precise risk stratification, and treatment success. In this review, we summarize the current advances, limitations, and challenges of AI models and raise potential strategies for improving their performance in each sector of the MICM pipeline. Finally, we share perspectives, highlight future directions, and call for extensive interdisciplinary cooperation to perfect AI with wise human-level strategies and promote its integration into the clinical workflow.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective To investigate the effects of transcutaneous auricular vagus nerve stimula-tion(taVNS)on preoperative anxiety and sleep quality in patients undergoing laparoscopic myomecto-my.Methods A total of 106 patients scheduled for elective laparoscopic myomectomy were randomly divided into active stimulation group(a-taVNS group,n=53)and sham stimulation group(s-taVNS group,n=53).Trait Anxiety Inventory(TAI)scores,State Anxiety Inventory(SAI)scores,Hos-pital Anxiety and Depression Scale-anxiety(HADS-A)scores,Amsterdam Preoperative Anxiety and Information Scale-anxiety(APAISa)scores,Athens Insomnia Scale(AIS)scores,hemodynamic parameters,and adverse reactions were evaluated before intervention(T0),30 min after interven-tion(T1),and the next morning(T2).The degrees of anxiety improvement(△SAI=SAIT0-SAIT1;△HADS-A=HADS-AT0-HADS-AT1;△APAISa=APAISaT0-APAISaT1)and sleep improvement(△AIS=AIST0-AIST2)were calculated,and their correlations were assessed.Results At T0,there were no significant differences in SAI,HADS-A,and APAISa scores between the two groups(P=0.376,0.682,0.144).At T1,there were significant differences in SAI and HADS-A scores between the two groups(adjusted P＜0.05),while there was no significant difference in APAISa scores(P=0.141).Compared with the s-taVNS group,the a-taVNS group had higher improvement values of △SAI,△HADS-A,and △APAISa(P＜0.001).Compared with T0,the AIS score de-creased and the incidence of sleep disorders decreased at T2 in the a-taVNS group(P＜0.05).Compared with the s-taVNS group,the AIS score and the proportion of patients with sleep disorders decreased at T2 in the a-taVNS group(P＜0.05).There was a positive correlation between the de-gree of anxiety improvement and the degree of sleep improvement in the a-taVNS group(P＜0.05),while there was no significant correlation in the s-taVNS group(P＞0.05).Compared with T0,sys-tolic blood pressure,diastolic blood pressure,and heart rate decreased at T1 in both groups,but there were no significant differences in these parameters between the two groups(P＞0.05).During the study period,no adverse events such as tinnitus,dizziness,headache,nausea,vomiting,or fa-cial flushing occurred in either group.Conclusion The method taVNS can improve preoperative anxiety and reduce the incidence of sleep disorders in patients undergoing laparoscopic myomectomy.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective:To discuss the relationship between three proinflammatory factors and muscle mass(MM)in the elderly patients with sarcopenic obesity and diabetes,and to provide theoretical basis for the development of clinical treatment protocols in the elderly patients with sarcopenic obesity and diabetes.Methods:The elderly patients with diabetes who visited our hospital from January 2021 to May 2023 were selected,including 41 patients with obesity and diabetes(OD group)and 46 patients with sarcopenic obesity and diabetes(SOD group);80 healthy subjects(control group)and 62 subjects with simple obesity(SO group)who underwent physical examination in our hospital during the same period were included.The clinical data of the subjects in four groups were compared,and the correlations between proinflammatory factors and MM and fat mass(FM)were analyzed.All the subjects were divided into sarcopenia group and normal group based on the presence of sarcopenia.Logistic regression model was used to analyze the independent influencing factors of sarcopenia;receiver operating characteristic(ROC)curve was drawn to determine the predictive value of the above factors for sarcopenia.Results:Compared with control group,the body mass index(BMI),FM and body fat percentage(BFP)of the subjects in SOD,OD and SO groups were significantly increased(P＜0.05);compared with control group,OD group and SO group,the appendicular skeletal muscle mass(ASM),appendicular skeletal muscle mass index(ASMI)and grip strength(GS)of the subjects in SOD group were significantly decreased(P＜0.05),and the levels of serum interleukin-6(IL-6),C-reactive protein(CRP)and tumor necrosis factor-α(TNF-α)were significantly increased(P＜0.05).In all the subjects,the IL-6,CRP and TNF-α were negatively correlated with ASMI(r=-0.589,r=-0.621,r=-0.620;P＜0.05),and positively correlated with BFP(r=0.252,r=0.221,r=0.147;P＜0.05).Compared with normal group,the ASM,ASMI and GS of the subjects in sarcopenia group were significantly decreased(P＜0.05),and the levels of serum proinflammatory factors IL-6,CRP and TNF-α were significantly increased(P＜0.05).The univariate Logistic regression analysis results showed that IL-6,CRP and TNF-α were the influencing factors of sarcopenia(P＜0.05).The multivariate Logistic regression analysis results showed that the increased levels of IL-6 and TNF-α were the independent risk factors for sarcopenia(OR＞1,P＜0.05).The ROC curve results showed that the area under the curve(AUC)values of IL-6,CRP and TNF-α were all＞0.700,indicating that the above indicators had good predictive value for sarcopenia.Conclusion:The increased levels of proinflammatory factors IL-6,CRP and TNF-α are associated with the decrease of MM in the elderly patients with sarcopenic obesity and diabetes,and IL-6 and TNF-α are the independent risk factors for the sarcopenia.