This article investigates the collaborative management of metabolic dysfunction-associated fatty liver disease （MAFLD） and chronic kidney disease （CKD）. As major public health issues worldwide， MAFLD and CKD are closely related in terms of epidemiology， pathogenesis， and management strategies， and however， there are still many challenges in the multidisciplinary collaborative management of the two diseases. This article systematically elaborates on the epidemiology of MAFLD and CKD， summarizes their common risk factors such as metabolic disorder， genetic susceptibility， and active metabolites， and reviews the mutual screening strategies and combined management models based on noninvasive imaging， serum markers， FIB-4 score， and liver stiffness measurement. In addition， this article summarizes the advances in the application of lifestyle intervention and new drugs （such as GLP-1 receptor agonists and SGLT-2 inhibitors） and emphasizes the importance of multidisciplinary collaboration in improving the prognosis of patients. Due to the close association between MAFLD and CKD， their joint management is crucial， and therefore， it is necessary to establish a multidisciplinary collaboration mechanism and implement the measures of precise screening， comprehensive treatment， and long-term monitoring， so as to improve the prognosis of patients and reduce the risk of complications. Finally， this article proposes that in the future， more effective combined treatment regimens should be explored to expand the clinical options for the co-management of the liver and the kidney.

In 2020， an international expert panel proposed to replace nonalcoholic fatty liver disease with metabolic associated fatty liver disease （MAFLD）. Recent studies have shown that there is a higher risk of chronic kidney disease （CKD） in the MAFLD population and that MAFLD is an independent risk factor for CKD. However， up to now， there are still no guidelines on the prevention and treatment of MAFLD-related CKD. Based on the Delphi method， the authors led a multidisciplinary team of 50 authoritative experts from 26 countries to reach a consensus on some open-ended research issues about the association between MAFLD and CKD， which can help to clarify the important clinical association between MAFLD and the risk of CKD and improve the understanding of the epidemiology， pathogenesis， management， and treatment of MAFLD and CKD， so as to establish a framework for the early prevention and management of these two common and interrelated diseases.

The limitations of antifungal drugs and severe drug resistance make the treatment of invasive fungal infections (IFIs) a great challenge. Itraconazole (ITZ), as a clinical first-line drug, has a wide range of antifungal activity, but it is still limited by adverse reactions such as liver and kidney toxicity, headache and abdominal pain due to its poor water solubility and easy to cause drug accumulation by injection. In this study, the amphiphilic polymer gallic acid-chitosan-cinnamaldehyde (GA-CS-CN) was prepared by amide reaction and Schiff-base reaction. The drug-loaded nanoparticles (GA-CS-CN/ITZ) were prepared by ultrasonic method. The properties of nanoparticles formulations and its in vitro antifungal activity were investigated in the study. Studies have shown that GA-CS-CN/ITZ is spherical, homogeneous and stable, and has good biological safety. The average particle size was 239.57 ± 31.37 nm, ITZ encapsulation efficiency was (93.41 ± 1.12)%, and the cumulative drug release was (62.25 ± 1.88)% at 48 h in vitro. The antifungal activity results of Candida albicans ATCC 10231 (C. albicans) showed that it had the optimal antifungal effect and could significantly enhance the antifungal activity of free drugs. GA-CS-CN/ITZ prepared in this study has excellent biological safety and anti-C. albicans performance, which provides a new choice for the treatment of C. albicans infection and has good application potential in the treatment of this fungal infection.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G⁺) or Gram-negative bacteria (G^-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G⁺ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G⁺ bacteria. Additionally, depletion of SCFAs-producing G⁺ bacteria rather than G^- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G⁺ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G⁺ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

Yeast autolysis affects the flavor and quality of beer. The regulation of yeast autolysis is a need for industrial beer production. Previous studies on brewer's yeast autolysis showed that the citric acid cycle-related genes had a great influence on yeast autolysis. To explore the contribution of isocitrate dehydrogenase genes in autolysis, the IDP1 and IDP2 genes were destroyed or overexpressed in typical lager yeast Pilsner. The destruction of IDP1 gene improved the anti-autolytic ability of yeast, and the anti-autolytic index after 96 h autolysis was 8.40, 1.5 times higher than that of the original strain. The destruction of IDP1 gene increased the supply of nicotinamide adenine dinucleotide phosphate (NADPH) and the NADPH/NADP⁺ ratio was 1.94. After fermentation, intracellular ATP level was 1.8 times higher than that of the original strain, while reactive oxygen species (ROS) was reduced by 10%. The destruction of IDP2 gene resulted in rapid autolysis and a decrease in the supply of NADPH. Anti-autolytic index after 96 h autolysis was 4.03 and the NADPH/NADP⁺ ratio was 0.89. After fermentation, intracellular ATP level was reduced by 8% compared with original strain, ROS was 1.3 times higher than that of the original strain. The results may help understand the regulation mechanism of citric acid cycle-related genes on yeast autolysis and provide a basis for the selection of excellent yeast with controllable anti-autolytic performance.
Humans ; Isocitrate Dehydrogenase/genetics* ; NADP ; Reactive Oxygen Species ; Autolysis ; Adenosine Triphosphate

Mitophagy is a process whereby cells selectively remove mitochondria through the mechanism of autophagy, which plays an important role in maintaining cellular homeostasis. In order to explore the effect of mitophagy genes on the antioxidant activities of Saccharomyces cerevisiae, mutants with deletion or overexpression of mitophagy genes ATG8, ATG11 and ATG32 were constructed respectively. The results indicated that overexpression of ATG8 and ATG11 genes significantly reduced the intracellular reactive oxygen species (ROS) content upon H₂O₂ stress for 6 h, which were 61.23% and 46.35% of the initial state, respectively. Notable, overexpression of ATG8 and ATG11 genes significantly increased the mitochondrial membrane potential (MMP) and ATP content, which were helpful to improve the antioxidant activities of the strains. On the other hand, deletion of ATG8, ATG11 and ATG32 caused mitochondrial damage and significantly decreased cell vitality, and caused the imbalance of intracellular ROS. The intracellular ROS content significantly increased to 174.27%, 128.68%, 200.92% of the initial state, respectively, upon H₂O₂ stress for 6 h. The results showed that ATG8, ATG11 and ATG32 might be potential targets for regulating the antioxidant properties of yeast, providing a new clue for further research.
Mitophagy/genetics* ; Saccharomyces cerevisiae/genetics* ; Antioxidants ; Hydrogen Peroxide/pharmacology* ; Reactive Oxygen Species

Objective:To explore the mechanism of dendritic cells(DCs),novel regulatory B cells(B10 cells)and Th17/Treg imbalance in the pathogenesis of patients with chronic obstructive pulmonary disease(COPD)and their correlation with lung function.Methods:According to the"Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease"a total of 93 COPD patients were prospectively selected from the Ninth People's Hospital of Suzhou from May 2019 to December 2021,and 50 healthy subjects were selected as the control group.The patients were followed up for 1 year to observe the occurrence of acute exacer-bation COPD(AECOPD),and divided them into stable COPD group and AECOPD group.The course of disease,modified British Medical Research Society dyspnea index(mMRC)classification,COPD assessment test(CAT)score,BODE index score,6 min walking distance(6MWD),arterial partial pressure of oxygen(PaO2),arterial carbon dioxide Partial pressure(PaCO2)were com-pared between the two groups;compared the levels of FEV1,FVC,FEV1/FVC,and the percentage of FEV1 to predicted value(FEV1/Pred)in the three groups with peripheral blood DCs,B10 cells,Th17 cells,Treg cells and Th17/Treg,IL-12,IL-10,IL-17A and TGF-β1 levels.To analyze the correlation between peripheral blood DCs cells,B10 cells and Th17/Treg imbalance and pulmonary function indexes in AECOPD group.Logistic regression analysis of independent risk factors for AECOPD.Results:A total of COPD pa-tients had AECOPD events(40.86%).The course of disease,mMRC grade,CAT score,BODE index score,and PaCO2 in AECOPD group were significantly higher than those in COPD stable group(P<0.05),6MWD and PaO2 were significantly lower than those in COPD group.The levels of FEV1,FVC,FEV1/FVC and FEV1/Pred in the AECOPD group were significantly lower than those in the stable COPD group and control group(P<0.05);the levels of FEV1,FVC,FEV1/FVC and FEV1/Pred in the stable COPD group were significantly lower than those in control group(P<0.05).DCs,B10 cells and Treg cells in AECOPD group were significantly lower than those in stable COPD group and control group,while Th17 expression level and Th17/Treg were significantly higher than that in stable COPD group and control group(P<0.05).DCs,B10 cells and Treg cells in stable COPD phase were significantly lower than those in control group,while Th17 expression level and Th17/Treg were significantly higher than control group(P<0.05).The ex-pression levels of IL-12,IL-10 and TGF-β1 in the AECOPD group were significantly lower than those in the stable COPD group and control group(P<0.05),while IL-17A was significantly higher than that in the stable COPD group and control group.The expression levels of IL-12,IL-10 and TGF-β1 in patients with stable COPD were significantly lower than control group,while IL-17A was signifi-cantly higher than control group(P<0.05).Pearson analysis showed that peripheral blood DCs,B10 cells were positively correlated with FEV1,FVC,FEV1/FVC and FEV1/Pred levels(P<0.05),while Th17/Treg was positively correlated with FEV1,FVC,FEV1/FVC and FEV1/Pred levels all were negatively correlated(P<0.05).Logistic regression analysis found that mMRC grade and Th17/Treg were independent risk factors of AECOPD(P<0.05).Conclusion:With the progression of COPD,DCs,B10 cells,Th17 cells,Treg cells and Th17/Treg gradually become unbalanced,resulting in disordered expression levels of pro-inflammatory and anti-inflamma-tory factors.Peripheral blood DCs and B10 cells were positively correlated with lung function levels,while Th17/Treg were negatively correlated with lung function levels.mMRC grade and Th17/Treg are independent risk factors of AECOPD.Therefore,actively inter-vening in the imbalanced state of immune function in patients has specific and important clinical significance in reducing the immune damage of lung tissue and promoting the improvement of lung function.

Objective:To investigate the relationship between peripheral blood helper T cell 1/helper T cell 2 (Th1/Th2), helper T cell 17/regulatory T cell (Th17/Treg) and efficacy of programmed death receptor 1 (PD-1) inhibitor in patients with advanced non-small cell lung cancer (NSCLC) combined with chronic obstructive pulmonary disease (COPD).Methods:The clinical data of 107 patients with advanced NSCLC combined with COPD who were admitted to Suzhou Ninth Hospital Affiliated to Soochow University from April 2021 to September 2022 were retrospectively analyzed. The patients were treated with PD-1 inhibitor, and they were categorized into the disease control group (82 cases) and the disease progression group (25 cases) according to the clinical efficacy. Th1/Th2, Th17/Treg and clinical data of patients before treatment were compared between the two groups, and logistic regression was used to analyze the independent influencing factors of patients' PD-1 inhibitor efficacy.Results:Th1/Th2 and Th17/Treg before treatment in the disease control group were higher than those in the disease progression group (12.49±1.14 vs. 7.04±1.06, t = 21.26, P < 0.001; 0.14±0.03 vs. 0.09±0.04, t = 6.72, P < 0.001). The proportions of patients with TNM stage Ⅳ, lymph node metastasis and brain metastasis in the disease progression group were higher than those in the disease control group (all P < 0.01). The results of multivariate logistic regression analysis showed that pre-treatment Th1/Th2 ( OR = 0.744, 95% CI 0.685-0.799, P < 0.001), pre-treatment Th17/Treg ( OR = 0.514, 95% CI 0.465-0.552, P < 0.001), TNM stage ( OR = 1.258, 95% CI 1.049-1.656, P = 0.048), lymph node metastasis ( OR = 1.790, 95% CI 1.223-2.734, P = 0.005), and brain metastasis ( OR = 1.640, 95% CI 1.184-2.348, P = 0.005) were independent influencing factors of PD-1 inhibitor efficacy in patients with advanced NSCLC combined with COPD. Conclusions:Patients with advanced NSCLC combined with COPD who have high Th1/Th2 and Th17/Treg before treatment have good outcomes with PD-1 inhibitor therapy.

Objective:To explore the relationship between soft markers found in the first trimester (11-13 + 6 gestational weeks) ultrasound screening and fetal adverse pregnancy outcomes. Methods:Single pregnancy fetuses were selected from the Multicenter Clinical Study of First Trimester Screening in China during August 2017 to August 2020. The types and detection rate of soft markers during the first trimester were compared. The correlation between positive soft markers and adverse pregnancy outcomes was analyzed by binary Logistics regression.Results:A total of 16 625 fetuses with complete follow-up outcomes were included in the group. Six hundred and seven ultrasonic soft markers were detected in 556 fetuses with positive soft markers during the first trimester, and the first four most frequently occurred were increased nuchal translucency (NT) (2.08%, 345/16 625), echogenic intracardiac focus (EIF) (0.94%, 156/16 625), hypoplasia of fetal nasal bone (0.20%, 34/16 625), single umbilical artery (SUA) (0.19%, 31/16 625). Among 556 fetuses, the incidence of adverse pregnancy outcome in fetuses with two or more positive soft markers was 32.50% (13/40), which was significantly higher than fetuses with single positive soft marker (11.05%, 57/516), and the difference was statistically significant (χ 2=5.055, P<0.001). The incidence of adverse pregnancy outcome in positive soft markers fetus associated with structural abnormalities was 80.77% (21/26), which was significantly higher than fetuses with isolated positive soft marker (12.08%, 64/530), and the difference was statistically significant (χ 2=90.310, P<0.001). Binary logistic regression analysis showed choroid plexus cyst (CPC), SUA, echogenic bowel (EB), absent/reversed a-wave of ductus venosus, hypoplasia of fetal nasal bone, increased NT, and EIF were closely related to the adverse pregnancy outcomes (all P<0.05). However, there were no significant correlations between tricuspid regurgitation (TR), pyelectasis (PYE) and fetal adverse pregnancy outcomes (all P>0.05). Conclusions:The ultrasonic soft markers during the first trimester are of great significance in predicting fetal adverse pregnancy outcomes. For multiple positive soft markers or positive soft markers combined with structural abnormalities, more attention should be paid to them and comprehensive evaluation is required to be carried out.

Lager yeast is the most popular yeast strain used for beer production in China. The flocculation of yeast plays an important role in cell separation at the end of fermentation. Therefore, appropriately enhancing the flocculation capability of the lager yeast without affecting its fermentation performance would be desirable for beer industry. Our previous study showed that the defect of gene RIM21 might contribute to the enhanced flocculation capability of a lager yeast G03. To further investigate the role of the RIM21 gene in flocculation of strain G03, this study constructed a RIM21-deleted mutant strain G03-RIM21Δ through homologous recombination. Deletion of RIM21 improved the flocculation capability of strain G03 during wort fermentation at 11 °C without changing its fermentation performance significantly. The expression of FLO5, Lg-FLO1 and some other genes involved in cell wall integrity pathway were up-regulated in strain G03-RIM21Δ. In addition, the disruption of RIM21 enhanced resistance of yeast cells to cell wall inhibitors. These results provide a basis for elucidating the flocculation mechanism of lager yeast under low-temperature fermentation conditions.
Beer ; Fermentation ; Flocculation ; Receptors, Cell Surface ; Saccharomyces/metabolism* ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism*