Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

The escalating pressure from global population growth, climate change, and resource consumption is intensifying the burden on traditional agricultural production. Against this backdrop, soil degradation and pollution present increasingly severe challenges, creating a vicious cycle with rising food demands. Maintaining soil health and its ecosystem services has thus become a critical prerequisite for achieving sustainable agriculture in the future. This review explores the impacts of soil carbon (C) and nitrogen (N) dynamics on soil microbial communities and their interactions. Soil C and N are key determinants of microbial diversity and community structure, intrinsically linked to soil C/N cycling, crop productivity, and ecological balance. Environmental factors such as nitrogen fertilizer application, organic matter amendment application, litter decomposition, elevated CO₂ concentrations, and nitrogen deposition significantly influence soil C and N dynamics. Changes in soil C and N content regulate microbial community dynamics and the synergistic, competitive, and antagonistic interactions among microorganisms. Meanwhile, microbial communities actively respond to alterations in soil C and N availability. The resulting shifts in microbial communities and their interactions subsequently regulate soil C/N cycling and ecosystem stability, ultimately influencing ecosystem functions. By elucidating the mechanisms underlying soil carbon-nitrogen-microbial interactions, this review significantly advances our understanding of soil ecosystem responses and feedback mechanisms in the context of global change, while also providing crucial practical guidance for enhancing soil fertility and promoting sustainable agricultural development through microbial regulation.
Soil Microbiology ; Nitrogen/metabolism* ; Carbon/metabolism* ; Soil/chemistry* ; Bacteria/growth & development* ; Fungi/metabolism* ; Ecosystem ; Fertilizers ; Agriculture

ObjectiveTo study the effect and mechanism of Yixintai on mitochondrial fission proteins in the rat model of chronic heart failure. MethodTen of 60 SD rats were randomly selected as the sham operation group， and the remaining 50 rats were subjected to ligation of the left anterior descending coronary artery for the modeling of heart failure post myocardial infarction. The successfully modeled rats were randomized into model， low-， medium-， and high-dose （1.4， 2.8， and 5.6 g·kg^-1， respectively） Yixintai， and trimetazidine （10 mg·kg^-1） groups. The rats were administrated with corresponding doses of drugs by gavage， and the rats in the model group and sham operation group were given an equal volume of normal saline by gavage for 28 consecutive days. Enzyme-linked immunosorbent assay （ELISA） was then employed to measure the levels of amino-terminal pro-B-type natriuretic peptide （NT-pro BNP）， B-type natriuretic peptide （BNP）， and adenosine triphosphate （ATP） in the serum. Color Doppler ultrasound imaging was conducted to examine the cardiac function indicators. Hematoxylin-eosin staining and Masson staining were conducted to observe the pathological changes in the heart， and Image J was used to calculate collagen volume fraction （CVF）. Transmission electron microscopy was employed to observe the ultrastructural changes of myocardial cells. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to measure the apoptosis rate of myocardial cells. Western blot was employed to determine the protein levels of mitochondrial fission protein 1 （Fis1） and mitochondrial fission factor （Mff） in the outer mitochondrial membrane of the myocardial tissue. ResultCompared with the sham operation group， the model group showed elevated levels of NT-pro BNP and BNP in the serum， decreased ATP content， left ventricular ejection fraction （LVEF）， and left ventricular fraction shortening （LVFS）， increased left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs）， disarrangement of myocardial cells， inflammatory cell infiltration， increased collagen fibers and CVF， damaged myocardium and mitochondria， and increased apoptosis rate of myocardial cells， and up-regulated expression of Fis1 and Mff in the cardiac tissue （P<0.01）. Compared with the model group， different doses of Yixintai and trimetazidine lowered the serum levels of NT-pro BNP and BNP （P<0.05）， increased the ATP content （P<0.05）， increased LVEF and LVFS （P<0.01）， decreased LVIDd and LVIDs （P<0.01）. Moreover， the drugs alleviated the myocardial inflammatory damage and fibrosis， reduced CVF （P<0.01）， repaired the myocardial mitochondrial structure， and decreased the apoptosis rate of myocardial cells （P<0.01）. Medium- and high-dose Yixintai and trimetazidine down-regulated the expression of Fis1 and Mff in the myocardial tissue （P<0.05）. ConclusionYixintai can improve mitochondrial structure， reduce myocardial cell apoptosis， and improve cardiac function by inhibiting the expression of Fis1 and Mff in the myocardial tissue.

Chronic heart failure(CHF)is a common and frequent clinical condition with complex pathogenesis.The micro-inflammatory state exists in the development of CHF and is manifested by a continuous increase in inflammatory proteins and inflammatory cytokines in the circulation,affecting the body's metabolism and immune function.Micro-inflammatory state of CHF belongs to the syndrome of deficiency in nature and excess in superficiality in the TCM field.The basic pathogenesis of CHF is"deficiency qi retention";the nature is the deficiency of heart energy and the superficiality is retention of qi,blood stagnation,phlegm,water and dampness,with"deficiency,stagnation and water"running throughout the disease.Therefore,based on the theory of"deficiency qi retention",this article took"reinforcing deficiency and removing stagnation"as its basic treatment method,regulated the body's immunity and inflammatory indicators such as serum high-sensitivity C-reactive protein,tumor necrosis factor-α,in order to alleviate the micro-inflammatory state,which is of great significance for the prevention and treatment of CHF.

Heart failure is a group of complex clinical syndromes in the middle and late stages of cardiovascular diseases.Mitochondrial homeostasis imbalance is one of the pathological mechanisms in the occurrence and development of heart failure.This article revolved around the"yin-yang theory"in TCM and explained the pathological mechanism of heart failure through mitochondrial homeostasis.Heart failure is the syndrome of deficiency in nature and excess in superficiality fundamental.Its basic pathogenesis is"yang deficiency and yin excess".Based on the deficiency of heart yang qi and the stagnation of yin pathogens,the combination of deficiency and excess runs through the entire disease.Mitochondrial homeostasis imbalance is a manifestation of yin-yang imbalance at the cellular micro level,mainly manifested as inhibition of mitochondrial biosynthesis,mitochondrial dynamics imbalance,mitophagy disorder,etc.,which affects mitochondrial structure and function and leads to abnormal myocardial energy metabolism.Therefore,based on the"yin-yang theory",the basic treatment method is to"tonify deficiency and damage excess"to regulate mitochondrial biosynthesis,mitochondrial dynamics,and mitophagy,thereby maintaining mitochondrial homeostasis and improving myocardial energy metabolism,which is of great significance for the prevention and treatment of heart failure.

Objective:This study aimed to overview the typical practies made by Europe on rare diseases cooperative researches and provide reference for the construction of rare disease research system in China.Methods:Through literature reviews and official website information, this study systematically summarized the contributions and outputs made by the framework of Europe cooperation in rare disease field.Results:Focusing on the needs of patients, the aim of international cooperation was to improve the ability of ″diagnosis, treatment, research and education″. inclnding multi-sourced special funding and project topic screening, expert networks setup and patient impower, research network construction and mutual promotion, information system modernization, etc.Conclusions:The eco-system of rare disease research in China is still under-construction. It is recommended to combine the characteristics of China′s healthcare system, optimize input strategies, empower patients, innovate mechanism, and speed up bioinformation technology.

Objective:To compare the image quality, radiation dose, and total iodine content of abdominal computed tomography (CT) enhancement scanning of overweight and obese patients with different scanning protocols, and to explore the optimal keV image serial for abdominal CT.Methods:A total of 90 overweight or obese patients [24 kg/m 2 ≤ body mass index (BMI) < 28 kg/m 2 or BMI ≥ 28 kg/m 2] were divied into groups A, B and C, with 30 patients in each group. Group A used Gemstone spectral imaging (GSI) mode and contrast medium with 320 mg I/ml, group B used low tube voltage mode (100 kVp) and contrast medium with 370 mg I/ml, and group C used conventional tube voltage mode (120 kVp) and contrast medium with 370 mg I/ml. Monochromatic energy images at 50-70 keV (5 keV interval) were reconstructed for the arterial and portal vein phases of group A. Radiation dose and total iodine content were recorded and calculated for the 3 groups. The region of interest was placed on the organ, blood vessel, and erector spinae muscle at same level. The CT values and image noise values were measured, and the contrast-to-noise ratio (CNR) was calculated. All images were scored subjectively in double-blinded by two radiologists. One-way analysis of variance or Kruskal-Wallis H test were used to compare The CT values, CNRs, and subjective scores of each subgroup image in group A, group B and group C, and the radiation doses and total iodine contents in 3 groups were compared. The optimal keV value for group A was selected. Results:At 50-60 keV, the CT values and CNRs of arterial and portal vein phases in group A were higher ( P < 0.05) than or similar to those in groups B and C ( P > 0.05), and the subjective scores were lower than those of groups B and C at 50 and 55 keV ( H = 34.47, 41.27, P < 0.05), whereas there was no statistically significant difference at 60 keV ( P > 0.05). At 65 and 70 keV, only the CT value and CNR of the renal cortex in group A at the 65 keV of arterial phase were higher than those in groups B and C ( F = 102.38, 29.47, P < 0.001). The subjective scores were not significantly between groups B and C ( P > 0.05). There were no statistically significant difference between CT values, CNRs, or subjective scores in group B and group C ( P > 0.05). The effective doses in groups A and B were 24.72% and 25.78% lower than those in group C, respectively. Compared to groups B and C, the total iodine content in group A decreased by 12.50% and 13.34%, respectively. Conclusions:GSI model combined with a low-concentration contrast medium in abdominal CT for overweight and obese patients can meet the image quality requirements while reducing patient total iodine content and radiation dose. The optimal keV value of enhanced abdominal CT for double phases was 60 keV.

ObjectiveTo study the medication rules of Professor. WANG Xingkuan and inherit his academic experience in the treatment of chest stuffiness and pain with the aid of the Traditional Chinese Medicine Inheritance Computing Platform V3.0 （TCMICS V3.0）. MethodThe original medical records of patients with angina pectoris in coronary heart disease （CHD） diagnosed and treated by Prof. WANG in the outpatient department of Hunan University of Chinese Medicine from 2017 to 2020 were collected and entered into the TCMICS V3.0. The rules of prescriptions and drugs were analyzed by the software. ResultA total of 1 044 prescriptions of Prof. WANG for the treatment of chest stuffiness and pain were collected. Most of the drugs were sweet and bitter in flavor and mainly acted on the lung meridian， followed by heart， spleen， liver， stomach， and kidney meridians. Among the prescriptions， Shengmaisan was the most commonly used classic prescription， and Xintongling No. Ⅲ was the top experienced prescription. High-frequency drugs mainly included Ophiopogonis Radix， Pinelliae Rhizoma， Salviae Miltiorrhizae Radix et Rhizoma， Trichosanthis Pericarpium， Coptidis Rhizoma， Schisandrae Chinensis Fructus， and Bupleuri Radix. The common doses of drugs were 3， 5， 10， and 15 g. The analysis of formulation rules revealed 129 combinations of common drugs， 58 combinations with confidence > 0.99， and the core drugs of common syndromes. Six core drug combinations were obtained by drug clustering. ConclusionProfessor WANG treats chest stuffiness and pain based on syndrome differentiation following the principles of benefiting Qi， nourishing Yin， eliminating phlegm， resolving stasis， soothing liver， and promoting bile secretion， reflecting his academic idea of "regulation of multiple organs and comprehensive treatment". The core prescriptions can be used for reference by clinical practitioners， but further clinical and experimental studies are still needed to verify their efficacy.

OBJECTIVES: With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T₁ weighted free-breathing star-volumetric interpolated breath hold examination (T₁WI star-VIBE) in identifying benign and malignant lung nodules. METHODS: We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T₁WI-VIBE, the contrast-enhanced T₁WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared. RESULTS: There were significant differences in unenhanced T₁WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T₁WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001). CONCLUSIONS T₁WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.
Adult ; Humans ; Retrospective Studies ; Magnetic Resonance Imaging ; Plasma ; Tomography, X-Ray Computed ; Lung

Objectives:the purpose of this study was to systematically evaluate the clinical value of cytokines in autoimmune diseases (AID). It was a kind of complex disease, and its pathogenesis involved cytokines, autoantibodies, immune cells and other immune factors. Especially some AID, such as Adult still′s disease (AOSD) and Takayasu arteritis(TA), had no specific biomarkers at present. This study was a retrospective case-control study.Methods:the data of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) in 834 AID patients from January 2019 to August 2022 were collected, and the serum levels of those cytokines in 30 healthy controls (HC) were detected at the same time. And AOSD, TA, systemic lupus erythematosus (SLE) and Behcet′s syndrome (BS) were divided into active group and inactive group. In addition, we also made a subgroup analysis of two important organs involved in SLE (kidney and nervous system). GraphPad Prism 9 and R 4.2.2 software were used. Nonparametric tests (Kruskal-Wallis H test, Mann-Whitney U test) were used to compare the differences among groups, and Dunn′s method was used to correct the false positive caused by multiple tests. Results:To compare the level of IL-6 in each group, except Behcet syndrome (BS) group and antiphospholipid syndrome (APS) group, the serum IL-6 level of AID group was higher than that of HC group, with antineutrophil cytoplasmic antibodies associated vasculitis(AAV) [3.85(2.00,8.55) pg/ml], idiopathic inflammatory myopathies(IIM) [7.80(2.50,6.50)pg/ml], IgG4-related disease(IgG4RD) [3.65(2.08,12.83) pg/ml], rheumatoid arthritis (RA) [5.50(2.20,16.10) pg/ml], SLE[4.70(2.75,16.55) pg/ml], Sj?gren syndrome(SS) [3.20(2.00,8.90) pg/ml], systemic sclerosis(SSc) [2.70(2.00,8.90) pg/ml], TA[3.40 (2.00,6.50) pg/ml], other AID diseases[4.40(2.00,11.10) pg/ml], especially AOSD [15.20(2.10, 39.20) pg/ml]. After correction, the differences were statistically significant ( P c<0.05). At the same time, the levels of serum TNF-α [7.40(5.60,10.95) pg/ml]and IL-10 [5.00(5.00, 7.58) pg/ml] in AOSD group were significantly higher than those in HC group[7.15(5.93,8.00) pg/ml,5.00(5.00,5.00) pg/ml] after correction ( P c<0.05). At the same time, the levels of serum TNF-α and IL-10 in AOSD group were higher than those in HC group. The serum levels of IL-6 and IL-8 in patients with active AOSD, BS, SLE and TA were significantly higher than those in patients without active disease (all P<0.05). In addition, the level of serum IL-8 in lupus nephritis group was significantly higher than that in non-lupus nephritis group ( P<0.05). At the same time, the serum levels of IL-6, IL-8 and TNF-α in neuropsychiatric lupus erythematosus group were significantly higher than those in non-neuropsychiatric lupus erythematosus group ( P<0.05), but there was no significant difference in IL-10 between neuropsychiatric lupus group and non-neuropsychiatric lupus erythematosus group. Conclusions:there was a close relationship between AID and cytokines. At present, the change of serum IL-6 level was the most classic one in clinical routine.