A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

MAFLD as part of systemic metabolic dysregulation.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS: The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS: The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

High-efficiency preparation of starch nanocrystals with small size and high crystallinity by ethanol-acid penetration and dry-heating pretreatment.

Ethanol-acid penetration and drying-heating treatment was developed to shorten the preparation time and improve the quality of starch nanocrystals (SNCs). After treatment by optimized parameters, including 40 % ethanol solution, 10.6 mM chloric acid, and heating time of 1.5 h or 2.0 h, the starches exhibited weakened internal structure and relatively complete crystalline structure. Compared with the regular preparation of only acid hydrolysis, the regular final yield (8.5 % after 5 days) was reached in 48 h and 12 h of the starch heated at 1.5 h and 2.0 h, respectively. The micromorphology, molecular weight, and crystalline structure evaluation demonstrated that the collected nanoparticles were indeed SNCs with smaller size and higher relative crystallinity than regular SNCs. Further analysis found that the SNCs had better crystalline lamellae, higher thermal stability, and lower proportion of phosphorus and sulfur atoms than regular SNCs. This provided a potential method for the high-efficiency preparation of SNCs.

Farnesoid X receptor activation protects against renal fibrosis via modulation of ß-catenin signaling.

OBJECTIVE: Activation of farnesoid X receptor (FXR), a bile acid nuclear receptor, may be implicated in the pathophysiology of diabetic nephropathy. We explored a possible role for FXR activation in preventing renal fibrosis in high fat diet (HFD)-fed mice. METHODS: We investigated the effects of HFD on mouse kidney and renal tubular epithelial cells both in vivo and in vitro, and observed the changes of FXR and ß-catenin pathway. FXR agonist was also used to alleviate this HFD-induced effect, and the interaction between FXR and ß-catenin was further verified. RESULTS: Mice were fed by a 60% kcal fat diet for 20 weeks developed the typical traits of metabolic syndrome with subsequent renal lipid accumulation and renal injury. Treatment with the FXR agonist CDCA or GW4064 decreased body weight, renal lipid accumulation, as well as renal injury. Moreover, renal ß-catenin signaling was activated and improved with FXR-agonist treatment in HFD-fed mice. To examine whether FXR affected ß-catenin signaling, and was involved in tubulo-interstitial fibrosis, we explored the FXR expression and function in ox-LDL induced-renal tubular injury. In rat proximal tubular epithelial cells (NRK-52E) stimulated by ox-LDL, FXR protein was decreased compared to control group, and phosphorylated (Ser675) ß-catenin was activated by ox-LDL in a dose- and time-dependent manner. Ox-LDL enhanced α-SMA and fibronectin expressions and reduced E-cadherin levels, whereas FXR agonism or FXR overexpression inhibited fibronectin and α-SMA expressions and restored E-cadherin. Moreover, FXR agonist treatment also decreased phosphorylated (Ser675) ß-catenin, nuclear translocation and ß-catenin-mediated transcription induced by ox-LDL in NRK-52E cells. We showed that FXR could bind with ß-catenin via the AF1 domain, and disrupt the assembly of the core ß-catenin/TCF4 complex. CONCLUSION: These experimental data suggest that FXR activation, via modulating ß-catenin signaling, may contribute to attenuating the development of lipid-mediated tubulo-interstitial fibrosis.

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease.

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community. Methods and Results: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD. Conclusions: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases.

Influence of macrophage polarization in herniated nucleus pulposus tissue on clinical efficacy after lumbar discectomy.

Background: Low back pain or sciatic pain because of lumbar intervertebral disc herniation (LDH) is caused by mechanical compression and/or an inflammatory component on the nerve root. However, it is difficult to define to what extent each component contributes to the pain. This study attempted to explore the effects of macrophage polarization on clinical symptoms in patients experiencing LDH after surgery, and investigated the association between macrophage cell percentages and clinical efficacy. Methods: This study retrospectively harvested nucleus pulposus (NP) tissue samples from 117 patients. Clinical symptoms and efficacy using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated at different time points preoperatively and postoperatively. CD68, CCR7, CD163, and CD206 were selected as macrophage phenotypic markers. Results: Seventy-six samples showed positive expression of macrophage markers in NP samples of patients with LDH, whereas 41 patients displayed negative results. No significant differences were detected between the two groups, involvement of several demographic data, and preoperative clinical findings. With respect to the macrophage-positive group, no significant correlation was detected between the positive rate of the four markers and the VAS score or ODI after surgery. However, patients with NP samples positive for CD68 and CCR7 expression showed significantly lower VAS scores 1 week after surgery compared with those in the negative group. Moreover, the improvement in VAS score showed a strong positive correlation with CD68- and CCR7-positive cell percentages. Conclusions: Our results indicated that pro-inflammatory M1 macrophages may be associated with the reduction of chronic pain after surgery. Therefore, these findings contribute to better personalized pharmacological interventions for patients with LDH, considering the heterogeneity of pain.

Novel urinary protein panels for the non-invasive diagnosis of non-alcoholic fatty liver disease and fibrosis stages.

BACKGROUND & AIMS: There is an unmet clinical need for non-invasive tests to diagnose non-alcoholic fatty liver disease (NAFLD) and individual fibrosis stages. We aimed to test whether urine protein panels could be used to identify NAFLD, NAFLD with fibrosis (stage F ≥ 1) and NAFLD with significant fibrosis (stage F ≥ 2). METHODS: We collected urine samples from 100 patients with biopsy-confirmed NAFLD and 40 healthy volunteers, and proteomics and bioinformatics analyses were performed in this derivation cohort. Diagnostic models were developed for detecting NAFLD (UPNAFLD model), NAFLD with fibrosis (UPfibrosis model), or NAFLD with significant fibrosis (UPsignificant fibrosis model). Subsequently, the derivation cohort was divided into training and testing sets to evaluate the efficacy of these diagnostic models. Finally, in a separate independent validation cohort of 100 patients with biopsy-confirmed NAFLD and 45 healthy controls, urinary enzyme-linked immunosorbent assay analyses were undertaken to validate the accuracy of these new diagnostic models. RESULTS: The UPfibrosis model and the UPsignificant fibrosis model showed an AUROC of .863 (95% CI: .725-1.000) and 0.858 (95% CI: .712-1.000) in the training set; and .837 (95% CI: .711-.963) and .916 (95% CI: .825-1.000) in the testing set respectively. The UPNAFLD model showed an excellent diagnostic performance and the area under the receiver operator characteristic curve (AUROC) exceeded .90 in the derivation cohort. In the independent validation cohort, the AUROC for all three of the above diagnostic models exceeded .80. CONCLUSIONS: Our newly developed models constructed from urine protein biomarkers have good accuracy for non-invasively diagnosing liver fibrosis in NAFLD.

Secondary bile acids improve risk prediction for non-invasive identification of mild liver fibrosis in nonalcoholic fatty liver disease.

BACKGROUND: Dysregulated bile acid (BA) metabolism has been linked to steatosis, inflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD). AIM: To determine whether circulating BA levels accurately stage liver fibrosis in NAFLD. METHODS: We recruited 550 Chinese adults with biopsy-proven NAFLD and varying levels of fibrosis. Ultra-performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs. RESULTS: Compared to those without fibrosis, patients with mild fibrosis (stage F1) had significantly higher levels of secondary BAs, and increased diastolic blood pressure (DBP), alanine aminotransferase (ALT), body mass index, and waist circumstance (WC). The combination of serum BAs with WC, DBP, ALT, or Homeostatic Model Assessment for Insulin Resistance performed well in identifying mild fibrosis, in men and women, and in those with/without obesity, with AUROCs 0.80, 0.88, 0.75 and 0.78 in the training set (n = 385), and 0.69, 0.80, 0.61 and 0.69 in the testing set (n = 165), respectively. In comparison, the combination of BAs and clinical/biochemical biomarkers performed less well in identifying significant fibrosis (F2-4). In women and in non-obese subjects, AUROCs were 0.75 and 0.71 in the training set, 0.65 and 0.66 in the validation set, respectively. However, these AUROCs were higher than those observed for the fibrosis-4 index, NAFLD fibrosis score, and Hepamet fibrosis score. CONCLUSIONS: Secondary BA levels were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum BAs and clinical/biochemical biomarkers for identifying mild fibrosis merits further assessment.

Macrophage polarization regulates intervertebral disc degeneration by modulating cell proliferation, inflammation mediator secretion, and extracellular matrix metabolism.

Macrophage infiltration and polarization have been increasingly observed in intervertebral disc (IVD) degeneration (IDD). However, their biological roles in IDD are still unrevealed. We harvested conditioned media (CM) derived from a spectrum of macrophages induced from THP-1 cells, and examined how they affect nucleus pulposus cells (NPCs) in vitro, by studying cell proliferation, extracellular matrix (ECM) synthesis, and pro-inflammation expression; and in vivo by injection CM in a rat IDD model. Then, high-throughput sequencing was used to detect differentially expressed genes (DEGs). Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks were used to further analysis. Higher CCR7+ (M1 marker) and CD206+ (M2 marker) cell counts were found in the degenerated human IVD tissues as compared with the control. Furthermore, the cell co-culture model showed M1CM attenuated NPC proliferation, downregulated the expression of ECM anabolic genes encoding aggrecan and collagen IIα1, upregulated the expression of ECM catabolic genes encoding MMP-13, and inflammation-related genes encoding IL-1ß, IL-6, and IL-12, while M2CM showed contrasting trends. In IDD model, higher histological scores and lower disc height index were found following M1CM treatment, while M2CM exhibited opposite results. M1CM injection decreased ECM anabolic and increased ECM catabolic, as well as the upregulation of inflammation-related genes after 8 weeks treatment, while M2CM slowed down these trends. Finally, a total of 637 upregulated and 655 downregulated genes were detected in M1CM treated NPCs, and 975 upregulated genes and 930 downregulated genes in the M2CM groups. The top 30 GO terms were shown and the most significant KEGG pathway was cell cycle in both groups. Based on the PPI analysis, the five most significant hub genes were PLK1, KIF20A, RRM2, CDC20, and UBE2C in the M1CM groups and RRM2, CCNB1, CDC20, PLK1, and UBE2C in the M2CM groups. In conclusion, macrophage polarization exhibited diverse roles in IDD progression, with M1CM exacerbating cell proliferation suppression and IVD degeneration, while M2CM attenuated IDD development. These findings may facilitate the further elucidation of the role of macrophage polarization in IDD, and provide novel insights into the therapeutic potential of macrophages.

[Colonization performance and pyrene degradation characteristics of Stenotrophomonas maltophilia PX1]. / å—œéº¦èŠ½å¯¡å »å•èƒžèŒPX1的降解芘特性及定殖效能.

We screened and identified an endophytic bacterium that could efficiently degrade PAHs, which would expand the library of polycyclic aromatic hydrocarbons (PAHs) degrading microorganisms and reduce the pollution risk of crops. Its degradation mechanism and colonization performance were preliminarily examined. The results showed that strain PX1 belonged to Stenotrophomonas maltophilia. The strain had broad spectrum ability to remove PAHs. In PAH mineral salt (MS) media, almost 100% naphthalene was degraded by strain PX1 after 7-d incubation. In a cultivation system solely containing phenanthrene of 50.0 mg·L-1, pyrene of 20.0 mg·L-1, fluoranthene of 20.0 mg·L-1 or benzo[a]pyrene of 10.0 mg·L-1, the degradation efficiency of phenanthrene, pyrene, fluoranthene and benzo[a]pyrene by strain PX1 reached 72.6%, 50.7%, 31.9%, and 12.9%, respectively. Pyrene was selected as PAHs model to study the degradation characteristics of strain PX1. Enzyme activity tests showed that the activities of phthalate dioxygenase, catechol-1,2-dioxygenase, and catechol-2,3-dioxygenase in strain PX1 were induced by pyrene. Some metabolic intermediates such as 4,5-epoxypyrene, 4,5-dihydroxypyrene, gentilic acid/protocatechuic acid, salicylic acid, cis-hexadienedioic acid/2-hydroxymyxofuroic acid semialdehyde, cis-2'-carboxyphenylpyruvic acid, 1-hydroxy-2-naphthoic acid, and salicylaldehyde were detected during the degradation of pyrene by strain PX1. Results of the seed soaking experiment showed that strain PX1 could efficiently colonize in Ipomoea aquatic and Triticum aestivum. After inoculated with strain PX1, the growth of I. aquatic and T. aestivum was significantly increased, and the pyrene concentration in I. aquatic, T. aestivum and MS media was reduced by 29.8%-50.7%, 52.4%-67.1% and 8.0%-15.3%, respectively. Our results suggested that strain PX1 degraded pyrene mainly through 'salicylate pathway' and 'phthalate pathway', and could be colonized into plants and promote plant growth.

Association of metabolic dysfunction-associated fatty liver disease with kidney disease.

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in more than 5% of hepatocytes in the absence of excessive alcohol consumption and other secondary causes of hepatic steatosis. In 2020, the more inclusive term metabolic (dysfunction)-associated fatty liver disease (MAFLD) - defined by broader diagnostic criteria - was proposed to replace the term NAFLD. The new terminology and revised definition better emphasize the pathogenic role of metabolic dysfunction and uses a set of definitive, inclusive criteria for diagnosis. Diagnosis of MAFLD is based on evidence of hepatic steatosis (as assessed by liver biopsy, imaging techniques or blood biomarkers and scores) in persons who are overweight or obese and have type 2 diabetes mellitus or metabolic dysregulation, regardless of the coexistence of other liver diseases or excessive alcohol consumption. The known association between NAFLD and chronic kidney disease (CKD) and our understanding that CKD can occur as a consequence of metabolic dysfunction suggests that individuals with MAFLD - who by definition have fatty liver and metabolic comorbidities - are at increased risk of CKD. In this Perspective article, we discuss the clinical associations between MAFLD and CKD, the pathophysiological mechanisms by which MAFLD may increase the risk of CKD and the potential drug treatments that may benefit both conditions.

The HSD17B13 rs72613567 variant is associated with lower levels of albuminuria in patients with biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Several susceptibility gene variants predisposing to nonalcoholic fatty liver disease (NAFLD) have been identified in chronic kidney disease (CKD). Evidence supports that 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) rs72613567 plays a role in NAFLD development by affecting lipid homeostasis. Since lipid droplets may accumulate in the kidneys and contribute to renal injury, we investigated the association between the HSD17B13 rs72613567 variant and markers of renal function/injury in NAFLD. METHODS AND RESULTS: We measured estimated glomerular filtration rate (eGFR), urinary/serum neutrophil gelatinase-associated lipocalin (NGAL), and urinary albumin-to-creatinine ratio (u-ACR) in individuals with biopsy-proven NAFLD. Multivariable regression analyses were undertaken to examine the associations between the HSD17B13 rs72613567 variant and markers of renal function/injury. Individuals were stratified by HSD17B13 rs72613567 genotypes into -/-, A/- and A/A groups. HSD17B13 rs72613567 genotypes were not significantly associated with eGFR and urinary/serum NGAL levels. Conversely, the prevalence of abnormal albuminuria in the A/- + A/A group was lower than in the -/- group (4.92% vs. 19.35%, p = 0.001). Additionally, the mean u-ACR levels were lower among carriers of the A/- or A/A genotypes with coexisting hypertension or diabetes, than among those with the -/- genotype. The risk of abnormal albuminuria (adjusted-odds ratio 0.16, p = 0.001) remained significantly lower in the A/- + A/A group after adjustment for established renal risk factors and histologic severity of NAFLD. CONCLUSION: HSD17B13 rs72613567: A allele is associated with a lower risk of having abnormal albuminuria, but not with lower eGFR or urinary/serum NGAL levels, in patients with biopsy-proven NAFLD.

MAFLD and risk of CKD.

BACKGROUND/AIMS: Whereas nonalcoholic fatty liver disease (NAFLD) is a multisystem disease, the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and extra-hepatic diseases is not known. The aim of this cross-sectional study was to compare the prevalence of chronic kidney disease (CKD) in patients with either MAFLD or NAFLD, and then to examine the association between the presence and severity of MAFLD and CKD and abnormal albuminuria. METHODS: A total of 12,571 individuals with complete biochemical and liver ultrasonography data from the Third National Health and Nutrition Examination Survey (1988-1994) were included in the analysis. Multivariable logistic regression analyses were performed to test the independence of associations between MAFLD or MAFLD severity as the key exposures and CKD (defined as either CKD stage ≥1 or stage ≥3) or abnormal albuminuria (urinary albumin-to-creatinine ratio ≥ 3 mg/mmol) as the outcomes. RESULTS: The prevalence of MAFLD and NAFLD was 30.2% (n = 3794) and 36.2% (n = 4552), respectively. MAFLD individuals had a lower eGFR (74.96 ±â€¯18.21 vs. 76.46 ±â€¯18.24 ml/min/1.73 m2, P < 0.001) and a greater prevalence of CKD (29.60% vs. 26.56%, P < 0.05) than NAFLD individuals. Similarly, there was a higher prevalence CKD in MAFLD than in non-metabolic dysfunction-associated NAFLD (P < 0.05). Notably, after adjustment for sex, age, ethnicity, alcohol intake and diabetes, the severity of MAFLD (i.e. NAFLD fibrosis score ≥ 0.676) was associated with 1.34-fold higher risk of prevalent CKD (P < 0.05). CONCLUSIONS: MAFLD identifies patients with CKD better than NAFLD. MAFLD and MAFLD with increased liver fibrosis score are strongly and independently associated with CKD and abnormal albuminuria.

Specialty construction and accomplishment of rehabilitation medicine in Fenglin Community Health Service Center of Shanghai Xuhui District / 中华全科医师杂志

Rehabilitation medicine is one of the most important specialties in community health institutions. This article introduces the 12 year′s development of rehabilitation medicine in Fenglin Community Health Service Center, focusing on the talent allocation, service capabilities, resource expansion, basic facilities, personnel recruiting, department operating, service scope, and its achievements and influence, to provide reference for planning and construction of featured specialty in community health service centers.

Ficus carica polysaccharide attenuates DSS-induced ulcerative colitis in C57BL/6 mice.

The Ficus carica polysaccharide (FCPS) components of the common fig fruit have been demonstrated to exhibit antioxidant and immunity-enhancing activities. However, it is unclear whether it could prevent the ulcerative colitis development. Here, we reported that 5 week orally administered FCPS (150-300 mg per kg bw) significantly prevented DSS-induced colitis in C57BL/6J mice by improving the colon length and suppressing the infiltration of inflammatory cells in the gut. FCPS treatment protected the goblet cells, elevated the expression of tight junction protein claudin-1, and suppressed the formation of cytokines including TNF-α and IL-1ß. FCPS supplementation significantly reformed the gut microbiome by enhancing the abundance of S24-7, Bacteroides, and Coprococus, and suppressing the abundance of Escherichia and Clostridium at the genus level. Consistently, the formation of beneficial microbial metabolites, short chain fatty acids, especially acetate and butyrate, were improved in FCPS-treated colitis mice. The correlation analysis indicated that the protective effects of FCPS on ulcerative colitis might be highly correlated with the microbiota composition changes and the formation of SCFAs. In conclusion, these results indicated that FCPS supplementation could be a promising nutritional strategy for reducing inflammatory bowel disease and the gut microbes play essential roles in providing these beneficial effects.

PNPLA3 rs738409 is associated with renal glomerular and tubular injury in NAFLD patients with persistently normal ALT levels.

BACKGROUND & AIMS: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism is associated with NAFLD severity and the PNPLA3 gene is expressed in the kidneys, but whether PNPLA3 rs738409 polymorphism is also associated with renal tubular injury (RTI) is uncertain. We assessed the effect of PNPLA3 genotypes on biomarkers of RTI and glomerular function in subjects with NAFLD who had either normal (nALT) or abnormal (abnALT) alanine aminotransaminase levels. METHODS: Two hundred and seventeen patients with histologically proven NAFLD of which 75 had persistently nALT (below upper limit of normal for 3 months) were included. Multivariable regression analyses were undertaken to test associations between PNPLA3 genotype and biomarkers of kidney dysfunction. RESULTS: The nALT patient group had higher urinary neutrophil gelatinase-associated lipocalin levels (u-NGAL, a biomarker of RTI) (P < .001), higher albuminuria (P = .039) and greater prevalence of chronic kidney disease (CKD; P = .046) than the abnALT group. The association between PNPLA3 GG genotype and risk of CKD and abnormal albuminuria remained significant after adjustment for kidney risk factors and severity of NAFLD histology, mostly in the nALT group. Similarly, PNPLA3 GG genotype was associated with higher u-NGAL levels in the nALT group, even after adjustment for the aforementioned risk factors and glomerular filtration-based markers (ß-coefficient: 22.29, 95% CI: 0.99-43.60, P = .041). CONCLUSION: Patients with NAFLD and persistently nALT, who carry the PNPLA3 rs738409 G allele, are at higher risk of early glomerular and tubular damage. We suggest PNPLA3 genotyping may help identify patients with NAFLD at higher risk of RTI.

Effects of compound probiotics on the weight, immunity performance and fecal microbiota of forest musk deer.

Probiotics are intended to provide health benefits when consumed, generally by improving or restoring the gut flora. The health problems of forest musk deer (FMD, Moschus berezovskii), a threatened species currently under conservation, restrict the development of captive musk deer. This study was conducted with the aim of analyzing the effects of forest musk deer compound probiotics (FMDPs) on weight, immunity performance and fecal microbiota in FMD by measuring average daily weight gain (ADG) and immune-related factors and by using high-throughput 16S rRNA sequencing to investigate differences in the fecal microbiota among the control group (4 samples), treatment group A (4 samples) and treatment group B (4 samples). The results showed that the ADG of treatment groups A and B was significantly higher than that of the control group (p = 0.032, p = 0.018). The increase in IgA and IgG levels in treatment group B was significantly higher than that in the control group (p = 0.02, p = 0.011). At the phylum and genus levels, the difference in bacterial community structure was significant between treatment group B and the control group. Both the alpha diversity and beta diversity results showed significant differences in the microbiota of FMD before and after FMDP feeding. In summary, the results indicated that FMDPs could promote the growth of growing FMD, improve immunity and balance the role of intestinal microbes.