MRI of GlycoNOE in the human liver using GraspNOE-Dixon.

PURPOSE: The objective of this study was to develop a new MRI technique for non-invasive, free-breathing imaging of glycogen in the human liver using the nuclear Overhauser effect (NOE). METHODS: The proposed method, called GraspNOE-Dixon, uses a novel MRI sequence that combines steady-state saturation-transfer preparation with multi-echo golden-angle radial stack-of-stars sampling. Multi-echo acquisition enables fat/water-separated imaging for quantification of water-specific NOE. Image reconstruction is performed using the improved golden-angle radial sparse parallel imaging (GRASP-Pro) technique to exploit spatiotemporal correlations in dynamic images. To evaluate the proposed technique, imaging experiments were first performed on glycogen phantoms, followed by in vivo studies involving healthy volunteers and patients with fatty liver disease. In addition, a comparative assessment of signal changes before and after a 12-h fasting period was performed. RESULTS: Evaluation experiments on glycogen phantoms showed a robust linear correlation between the NOE signal and glycogen concentration. In vivo experiments demonstrated motion-robust NOE-weighted images, with potential for further acceleration. In subjects with varying liver fat content, the fat/water separation approach resulted in distortion-free Z-spectra, enabling the quantification of glycogen NOE. An approximately one-third reduction in the NOE signal was observed following a 12-h fasting period, consistent with a decrease in glycogen level. CONCLUSION: This study introduces a clinically feasible imaging technique, GraspNOE-Dixon, for free-breathing volumetric multi-echo imaging of hepatic glycogen at 3 T. The motion robust imaging technique developed here may also have applications in other body areas beyond liver imaging.

DCE-MRI of the liver with sub-second temporal resolution using GRASP-Pro with navi-stack-of-stars sampling.

Respiratory motion-induced image blurring and artifacts can compromise image quality in dynamic contrast-enhanced MRI (DCE-MRI) of the liver. Despite remarkable advances in respiratory motion detection and compensation in past years, these techniques have not yet seen widespread clinical adoption. The accuracy of image-based motion detection can be especially compromised in the presence of contrast enhancement and/or in situations involving deep and/or irregular breathing patterns. This work proposes a framework that combines GRASP-Pro (Golden-angle RAdial Sparse Parallel MRI with imProved performance) MRI with a new radial sampling scheme called navi-stack-of-stars for free-breathing DCE-MRI of the liver without the need for explicit respiratory motion compensation. A prototype 3D golden-angle radial sequence with a navi-stack-of-stars sampling scheme that intermittently acquires a 2D navigator was implemented. Free-breathing DCE-MRI of the liver was conducted in 24 subjects at 3T including 17 volunteers and 7 patients. GRASP-Pro reconstruction was performed with a temporal resolution of 0.34-0.45 s per volume, whereas standard GRASP reconstruction was performed with a temporal resolution of 15 s per volume. Motion compensation was not performed in all image reconstruction tasks. Liver images in different contrast phases from both GRASP and GRASP-Pro reconstructions were visually scored by two experienced abdominal radiologists for comparison. The nonparametric paired two-tailed Wilcoxon signed-rank test was used to compare image quality scores, and the Cohen's kappa coefficient was calculated to evaluate the inter-reader agreement. GRASP-Pro MRI with sub-second temporal resolution consistently received significantly higher image quality scores (P < 0.05) than standard GRASP MRI throughout all contrast enhancement phases and across all assessment categories. There was a substantial inter-reader agreement for all assessment categories (ranging from 0.67 to 0.89). The proposed technique using GRASP-Pro reconstruction with navi-stack-of-stars sampling holds great promise for free-breathing DCE-MRI of the liver without respiratory motion compensation.

Free-breathing time-resolved 4D MRI with improved T1-weighting contrast.

This work proposes MP-Grasp4D (magnetization-prepared golden-angle radial sparse parallel 4D) MRI, a free-breathing, inversion recovery (IR)-prepared, time-resolved 4D MRI technique with improved T1-weighted contrast. MP-Grasp4D MRI acquisition incorporates IR preparation into a radial gradient echo sequence. MP-Grasp4D employs a golden-angle navi-stack-of-stars sampling scheme, where imaging data of rotating radial stacks and navigator stacks (acquired at a consistent rotation angle) are alternately acquired. The navigator stacks are used to estimate a temporal basis for low-rank subspace-constrained reconstruction. This allows for the simultaneous capture of both IR-induced contrast changes and respiratory motion. One temporal frame of the imaging volume in MP-Grasp4D MRI is reconstructed from a single stack and an adjacent navigator stack on average, resulting in a nominal temporal resolution of 0.16 seconds per volume. Images corresponding to the optimal inversion time (TI) can be retrospectively selected for providing the best image contrast. Reader studies were conducted to assess the performance of MP-Grasp4D MRI in liver imaging across 30 subjects in comparison with standard Grasp4D MRI without IR preparation. MP-Grasp4D MRI received significantly higher scores (P < 0.05) than Grasp4D in all assessment categories. There was a moderate to almost perfect agreement (kappa coefficient from 0.42 to 0.9) between the two readers for image quality assessment. When the scan time is reduced, MP-Grasp4D MRI preserves image contrast and quality, demonstrating additional acceleration capability. MP-Grasp4D MRI improves T1-weighted contrast for free-breathing time-resolved 4D MRI and eliminates the need for explicit motion compensation. This method is expected to be valuable in different MRI applications such as MR-guided radiotherapy.

Application of individual brain connectome in chronic ischemia: mapping symptoms before and after reperfusion.

How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno-occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity-based and pathological distortion-independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single-subject level. Thirty-three machine-learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature-based model for long-term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate "fingerprints" of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

Poly(ethylene oxide)- and Polyzwitterion-Based Thermoplastic Elastomers for Solid Electrolytes.

In this article, ABA triblock copolymer (tri-BCP) thermoplastic elastomers with poly(ethylene oxide) (PEO) middle block and polyzwitterionic poly(4-vinylpyridine) propane-1-sulfonate (PVPS) outer blocks were synthesized. The PVPS-b-PEO-b-PVPS tri-BCPs were doped with lithium bis-(trifluoromethane-sulfonyl) imide (LiTFSI) and used as solid polyelectrolytes (SPEs). The thermal properties and microphase separation behavior of the tri-BCP/LiTFSI hybrids were studied. Small-angle X-ray scattering (SAXS) results revealed that all tri-BCPs formed asymmetric lamellar structures in the range of PVPS volume fractions from 12.9% to 26.1%. The microphase separation strength was enhanced with increasing the PVPS fraction (fPVPS) but was weakened as the doping ratio increased, which affected the thermal properties of the hybrids, such as melting temperature and glass transition temperature, to some extent. As compared with the PEO/LiTFSI hybrids, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids could achieve both higher modulus and higher ionic conductivity, which were attributed to the physical crosslinking and the assistance in dissociation of Li+ ions by the PVPS blocks, respectively. On the basis of excellent electrical and mechanical performances, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids can potentially be used as solid electrolytes in lithium-ion batteries.

The Application of Nanoparticles Targeting Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.

Low thyroid function is associated with metabolic dysfunction-associated steatotic liver disease.

Background and Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is recently introduced to better highlight the pathogenic significance of cardiometabolic dysfunction, as compared with non-alcoholic fatty liver disease. This study aimed to investigate the association between low thyroid function and MASLD in the new context. Methods: We recruited 2901 participants for our retrospective cohort study from 2016 to 2021. Participants were divided into strict-normal thyroid function and low thyroid function groups (low-normal thyroid function, subclinical hypothyroidism) based on initial thyroid stimulating hormone (TSH) levels, respectively. Cox regression models were used to estimate the hazard ratios (HRs) and 95% CI. Results: During a median follow-up of 15.6 months, 165 (8.9%) strict-normal thyroid function subjects and 141 (13.4%) low thyroid function subjects developed MASLD; this result was statistically relevant (P < 0.05). Univariate regression analysis showed that low thyroid function and subclinical hypothyroidism were statistically significantly associated with MASLD (low thyroid function: HR1.53; 95% CI 1.22-1.92; subclinical hypothyroidism: HR1.95; 95% CI 1.47-2.60). Conclusions: MASLD is associated with low thyroid function and the relationship between MASLD and low thyroid function is independent.

Disease trajectory of high neuroticism and the relevance to psychiatric disorders: A retro-prospective cohort study.

BACKGROUND: Neuroticism is a psychological personality trait that has a significant impact on public health and is also a potential predisposing factor for adverse disease outcomes; however, comprehensive studies of the subsequently developed conditions are lacking. The starting point of disease trajectory in terms of genetic variation remains unclear. METHOD: Our study included 344,609 adult participants from the UK Biobank cohort who were virtually followed up from January 1, 1997. Neuroticism levels were assessed using 12 items from the Eysenck Personality Questionnaire. We performed a phenome-wide association analysis of neuroticism and subsequent diseases. Binomial tests and logistic regression models were used to test the temporal directionality and association between disease pairs to construct disease trajectories. We also investigated the association between polygenic risk scores (PRSs) for five psychiatric traits and high neuroticism. RESULTS: The risk for 59 diseases was significantly associated with high neuroticism. Depression, anxiety, irritable bowel syndrome, migraine, spondylosis, and sleep disorders were the most likely to develop, with hazard ratios of 6.13, 3.66, 2.28, 1.74, 1.74, and 1.71, respectively. The disease trajectory network revealed two major disease clusters: cardiometabolic and chronic inflammatory diseases. Medium/high genetic risk groups stratified by the PRSs of four psychiatric traits were associated with an elevated risk of high neuroticism. We further identified eight complete phenotypic trajectory clusters of medium or high genetic risk for psychotic, anxiety-, depression-, and stress-related disorders. CONCLUSION: Neuroticism plays an important role in the development of somatic and mental disorders. The full picture of disease trajectories from the genetic risk of psychiatric traits and neuroticism in early life to a series of diseases later provides evidence for future research to explore the etiological mechanisms and precision management.

Optimized Design of Solid-Liquid Dual-Impeller Mixing Systems for Enhanced Efficiency.

Flow interferences occur in the dual-impeller stirred tank between paddles as well as between paddles and baffles and the tank wall, leading to inefficient utilization of the stirring energy. To address this issue, this study investigates the flow characteristics within the mixing tank using Euler-Euler numerical simulation and the particle image velocimetry (PIV) experimental method. The three-dimensional nonconstant flow characteristics are analyzed to optimize the critical stirrer geometry. By employing the Sobol method, an approximate model is established for sensitivity analysis to identify key parameters affecting the solid-liquid dual-impeller stirred tank's performance. Numerical simulations demonstrate that the optimized stirred tank exhibits a significantly improved solid-liquid suspension capacity and considerably reduces flow losses near the wall and baffle areas. Under the designated conditions, the cloud height is increased by 8.7%, and power consumption is reduced by 15.6% compared to the prototype. PIV tests performed on the stirred tank before and after optimization confirmed the reliability of the obtained optimization results. The primary objective of this study is to enhance mixing efficiency and homogeneity in solid-liquid mixing tanks while concurrently minimizing energy consumption and cost. These results validate the feasibility of employing a multiobjective optimal design approach that combines the RBF agent model with the Sobol method. The findings offer valuable insights for the design of similar mixing tanks.

Individualised evaluation based on pathophysiology for moyamoya vasculopathy: application in surgical revascularisation.

BACKGROUND: Although bypass surgery is an effective treatment for moyamoya vasculopathy (MMV), the incidence of postoperative complications is still high. This study aims to introduce a novel evaluating system based on individualised pathophysiology of MMV, and to assess its clinical significance. METHODS: This multicentre, prospective study enrolled adult patients with MMV from Huashan Hospital, Fudan University and National Center for Neurological Disorders, China between March 2021 and February 2022. Multimodal neuroimages containing structural and functional information were used to evaluate personalised disease severity and fused to localise the surgical field, avoid invalid regions and propose alternative recipient arteries. The recipient artery was further selected intraoperatively by assessing regional haemodynamic and electrophysiological information. The preanastomosis and postanastomosis data were compared with assist with the postoperative management. Patients who received such tailored revascularisations were included in the novel group and the others were included in the traditional group. The 30-day surgical outcomes and intermediate long-term follow-up were compared. RESULTS: Totally 375 patients (145 patients in the novel group and 230 patients in the traditional group) were included. The overall complication rate was significantly lower in the novel group (p˂0.001). In detail, both the rates of postoperative infarction (p=0.009) and hyperperfusion syndrome (p=0.010) were significantly lower. The functional outcomes trended to be more favourable in the novel group, though not significantly (p=0.260). Notably, the proportion of good functional status was higher in the novel group (p=0.009). Interestingly, the preoperative statuses of perfusion and metabolism around the bypass area were significantly correlated with the occurrence of postoperative complications (P˂0.0001). CONCLUSIONS: This novel evaluating system helps to identify appropriate surgical field and recipient arteries during bypass surgery for MMV to achieve better haemodynamic remodelling and pathophysiological improvement, which results in more favourable clinical outcomes.

Microphase Separation with Sub-3 nm Microdomains in Comb-Like Poly(n-alkyl acrylate) Homopolymers Facilitated by Charged Junction Groups between the Main Chains and Side Chains.

The phase structure with a small domain size in polymers is expected to provide a template for lithography to fabricate electronic devices, while the uniformity and thermal stability of the phase structure are vital in lithography. In this work, we report an accurately microphase-separated system of comb-like poly(ionic liquid) (PIL)-based homopolymers containing imidazolium cation junctions between the main chain parts and the long alkyl side chains, poly(1-((2-acryloyloxy)ethyl)-3-alkylimidazolium bromide) (P(AOEAmI-Br)). The ordered hexagonally packed cylinder (HEX) and lamellar (LAM) structures with small domain sizes (sub-3 nm) were successfully achieved. Since the microphase separation was induced by the incompatibility between the main chain parts and the hydrophobic alkyl chains, the microdomain spacing of the ordered structure was independent of the molecular weight and molecular weight distribution of P(AOEAmI-Br) homopolymers and could be precisely regulated by changing the length of the alkyl side chains. Importantly, the microphase separation was promoted by the charged junction groups; thus, the phase structure and domain size of P(AOEAmI-Br) exhibited excellent thermal stability.

Evaluation of glymphatic-meningeal lymphatic system with intravenous gadolinium-based contrast-enhancement in cerebral small-vessel disease.

OBJECTIVE: To investigate the feasibility of using noninvasive neuroimaging methods in visualizing and evaluating the clearance of the glymphatic-meningeal lymphatic system (GMLS) in patients with arteriosclerotic cerebral small-vessel disease (CSVD) and controls. METHODS: This observational study recruited patients with high-burden CSVD and controls (age 50-80 years). At multiple time points before and after intravenous administration of a contrast agent, three-dimensional (3D) brain volume T1-weighted imaging and 3D Cube T2-fluid attenuated inversion recovery imaging were performed to visualize and assess the clearance of the glymphatics and meningeal lymphatic vessels (mLVs). We measured the signal intensity ratio (SIR) of four regions of interest representing the glymphatics and mLVs at each time point. The clearance rate at 24 h (CR24h) and changes in the SIR from baseline to 24 h (∆SIR) were defined as the clearance function. The analysis of variance was used to evaluate the group differences after adjusting for hypertension. RESULTS: A total of 20 CSVD patients and 15 controls were included. Cortical periarterial enhancement and the enhancement of enlarged perivascular spaces in the basal ganglia were respectively observed in 11 (55.00%) and 16 (80.00%) CSVD patients, but in none of controls. All CSVD patients and most of controls (80.00%) showed cortical perivenous enhancement. Para-sinus enhancement was observed in all participants. CSVD patients showed lower CR24h and higher ∆SIR of the glymphatics and mLVs (all p < 0.05). CONCLUSION: The impaired drainage of the GMLS in patients with high-burden CSVD could be visually evaluated using noninvasive neuroimaging methods with intravenous gadolinium-based contrast-enhancement. CLINICAL RELEVANCE STATEMENT: Dynamic intravenous contrast-enhanced MRI could visually evaluate the impaired drainage of the glymphatic-meningeal lymphatic system in patients with high-burden cerebral small-vessel disease and could help to explore a new therapeutic target. KEY POINTS: • Signal intensity changes in regions representing the glymphatic-meningeal lymphatic system (GMLS) can reflect the drainage function based on contrast-enhanced 3D-FLAIR and 3D T1-weighted MRI. • Impaired drainage of the GMLS in patients with high-burden CSVD can be visually evaluated using dynamic intravenous contrast-enhanced MRI. • This direct, noninvasive technique could serve as a basis for further GMLS studies and could help to explore a new therapeutic target in CSVD patients.

Chemical Constituents and Their Biological Activities from Genus Styrax.

Plants from the genus Styrax have been extensively used in folk medicines to treat diseases such as skin diseases and peptic ulcers and as an antiseptic and analgesic. Most Styrax species, especially Styrax tonkinensis, which is used as an expectorant, antiseptic, and analgesic in Chinese traditional medicine, could screen resin after external injury. Styrax is also used in folk medicines in Korea to treat sore throat, bronchitis, cough, expectoration, paralysis, laryngitis, and inflammation. Different parts of various Styrax species can be widely employed for ethnopharmacological applications. Moreover, for ethnopharmacological use, these parts of Styrax species can be applied in combination with other folk medicines. Styrax species consist of versatile natural compounds, with some of them exhibiting particularly excellent pharmacological activities, such as cytotoxic, acetylcholinesterase inhibitory, antioxidant, and antifungal activities. Altogether, these exciting results indicate that a comprehensive review of plants belonging to this genus is essential for helping researchers to continuously conduct an in-depth investigation. In this review, the traditional uses, phytochemistry, corresponding pharmacological activities, and structure-activity relationships of different Styrax species are clarified and critically discussed. More insights into potential opportunities for future research are carefully assessed.

The role of circular RNA in tumor microenvironment and immunotherapy.

Cancer immunotherapy has favorable efficacy in various types of tumors, and has become an important weapon in the treatment of tumors in recent years. Long noncoding RNAs and microRNAs have been identified to play important roles in regulating cancer immunotherapy. Circular RNAs (circRNAs) are involved in the pathological process of many diseases, especially cancer. Many functions of circRNAs have been extensively studied. However, the functions of circRNAs in the tumor microenvironment and cancer immunotherapy do not appear to be fully elucidated. Therefore, we review the roles of circRNAs in tumor microenvironment and cancer immunotherapy.

Rapid 3D T1 mapping using deep learning-assisted Look-Locker inversion recovery MRI.

PURPOSE: Conventional 3D Look-Locker inversion recovery (LLIR) T1 mapping requires multi-repetition data acquisition to reconstruct images at different inversion times for T1 fitting. To ensure B1 robustness, sufficient time of delay (TD) is needed between repetitions, which prolongs scan time. This work proposes a novel deep learning-assisted LLIR MRI approach for rapid 3D T1 mapping without TD. THEORY AND METHODS: The proposed approach is based on the fact that T 1 * $$ {\mathrm{T}}_1^{\ast } $$ , the effective T1 in LLIR imaging, is independent of TD and can be estimated from both LLIR imaging with and without TD, while accurate conversion of T 1 * $$ {\mathrm{T}}_1^{\ast } $$ to T1 requires TD. Therefore, deep learning can be used to learn the conversion of T 1 * $$ {\mathrm{T}}_1^{\ast } $$ to T1 , which eliminates the need for TD. This idea was implemented for inversion-recovery-prepared Golden-angel RAdial Sparse Parallel T1 mapping (GraspT1 ). 39 GraspT1 datasets with a TD of 6 s (GraspT1 -TD6) were used for training, which also incorporates additional anatomical images. The trained network was applied for T1 estimation in 14 GraspT1 datasets without TD (GraspT1 -TD0). The robustness of the trained network was also tested. RESULTS: Deep learning-based T1 estimation from GraspT1 -TD0 is accurate compared to the reference. Incorporation of additional anatomical images improves the accuracy of T1 estimation. The technique is also robust against slight variation in spatial resolution, imaging orientation and scanner platform. CONCLUSION: Our approach eliminates the need for TD in 3D LLIR imaging without affecting the T1 estimation accuracy. It represents a novel use of deep learning towards more efficient and robust 3D LLIR T1 mapping.

Electrostatic crosslinking-enabled highly asymmetric lamellar nanostructures of polyzwitterionic block copolymers for lithography.

For the bulk self-assembly of traditional diblock copolymers (di-BCPs), lamellar structures only occur when two constituents have similar volume fractions (f) and two alternating layers tend to have similar thicknesses. Highly asymmetric lamellar (A-LAM) structures, in which the thickness of one layer is several times higher than the other, are hardly formed in di-BCPs, while they have potential applications in nanolithography. In this work, A-LAM structures with different dimensions were constructed using a type of simple linear di-BCP, polystyrene-b-poly(4-vinylpyridine)propane-1-sulfonate (PS-b-PVPS) with the polyzwitterionic block PVPS in minority. The origin of the A-LAM structure was ascribed to the electrostatic crosslinking and confirmed by doping PS-b-PVPS block copolymers (BCPs) with N-butyl pyridinium methane sulfonate (BPMS). The morphology of compositionally asymmetric PS-b-PVPS BCPs changed from A-LAM to cylindrical structures upon salt-doping, i.e. the phase behavior of common BCPs was recovered. In addition, the morphologies of PS-b-PVPS BCPs with similar molecular weights but varied compositions were also studied, and only two kinds of structures (lamellar or ill-defined spherical structure) were observed when the volume fraction of PVPS (fPVPS) was less than 0.5, and the composition range for the formation of the lamellar structure was found to be fPVPS ≥ 0.188.

The mechanism of modified Gan Cao Fu Zi Decoction in the treatment of rheumatoid arthritis based on network pharmacology and experimental validation / 药学学报

We used network pharmacology to predict the mechanism in the treatment of rheumatoid arthritis (RA) via modified Gan Cao Fu Zi Decoction (GCFZ), and validated the results of the analysis and explored the pharmacodynamic effects of GCFZ through animal experiments. Firstly, TCMID, SymMap, HERB, STITCH and GEO databases were utilized to obtain the target genes of GCFZ for the treatment of RA, which yielded a total of 1 250 differentially expressed genes for RA, 534 genes for GCFZ targets and 83 intersecting genes. Then functional enrichment analysis of the intersecting genes was performed through GO and KEGG databases, and the results revealed that GCFZ and its active ingredients mainly functioned through cytokine pathways, where chemokine signaling pathway and tumor necrosis factor (TNF) signaling pathway were enriched with a high number of genes. Cytoscape 3.8.0 software was used to construct the drug-target-disease network and screen key proteins, which included TNF, C-X-C chemokine ligand 8 (CXCL8), C-X-C chemokine ligand 10 (CXCL10), C-C chemokine ligand 5 (CCL5), C-X-C chemokine ligand 2 (CXCL2) and C-X-C chemokine receptor type 4 (CXCR4). The molecular docking technology was used to confirm the binding ability of the main active ingredients of GCFZ to the core proteins. Additionally, the therapeutic effects of GCFZ in low (4 g·kg-1), medium (8 g·kg-1) and high (16 g·kg-1) dose groups were investigated by constructing the collagen-induced arthritis (CIA) rat model. X-ray imaging approach, HE staining and Safranin O-Fast Green staining showed that GCFZ treatment significantly improved bone destruction, synovial hyperplasia and cartilage damage in CIA rats, while immunofluorescence results showed that GCFZ treatment could regulate the expression of TNF, CXCL8 and CCL5. In summary, our results indicate that GCFZ contains a variety of small molecule pharmacodynamic substances, which can exert therapeutic effects via multiple targets and pathways, and obviously reduce the symptoms of arthritis in CIA rats. This animal experiment of our research was approved by the Experimental Animal Management and Ethics Committee of Bengbu Medical College.

Traditional Chinese Medicine Treats Chronic Atrophic Gastritis via Multiple Pathways / 中国实验方剂学杂志

ObjectiveTo mine the compatibility rules of patented traditional Chinese medicine (TCM) compound prescriptions for treating chronic atrophic gastritis (CAG) by systems pharmacology and molecular docking methods, and predict the targets and molecular mechanisms of Chinese medicinals with different efficacy in the treatment of CAG. MethodThe TCM compound prescriptions for treating CAG were extracted from the patent system of the China National Intellectual Property Administration. The active components and targets of the prescriptions were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrative Database (TCMID), and UniProt. The candidate targets and pathways of CAG were obtained from GeneCards, DisGeNet, Online Mendelian Inheritance in Man (OMIM), MalaCards, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome. The gene ontology (GO) functional annotation and KEGG pathway enrichment were realized by R Studio 4.1.2. STRING11.0 was employed to build the protein-protein interaction (PPI) network, and AutoDock Vina 4.2.6 was used for the docking between key targets and components. ResultA total of 228 TCM compound prescriptions for treating CAG were extracted. The medicinals used in these prescriptions mainly had warm or cold nature, bitter or sweet taste, tropism to the spleen, stomach, and liver meridians, and the efficacy of tonifying Qi, regulating Qi movement, clearing heat, and activating and toniying blood. The prescriptions mainly treated CAG via p53, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), forkhead box protein O (FoxO), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1 (HIF-1) signaling pathways. Molecular docking results confirmed that the active components in the prescriptions had docking activities with key receptor proteins. ConclusionThis study preliminarily analyzed the compatibility rules of TCM compound prescriptions in the treatment of CAG. The medicinals with different efficacy treat CAG by regulating cell proliferation, apoptosis, and oxidative stress response, preventing carcinogen production, promoting gastric acid secretion, and improving local microcirculation in a multi-target, multi-pathway, multi-link manner. The findings facilitate the research on the TCM treatment of CAG.

Evolutionary Law of Syndrome and Syndrome Elements during the Malignant Transformation of Chronic Hepatitis B / 中医杂志

ObjectiveTo clarify the evolutionary laws of syndromes and syndrome elements at different stages during the malignant transformation of chronic hepatitis B （CHB）. MethodsA total of 671 patients with hepatitis B virus infection， who were admitted to the outpatient and inpatient departments of Dongzhimen Hospital of Beijing University of Chinese Medicine and The Fifth Medical Center of Chinese PLA General Hospital from July 1st， 2020 to June 30th， 2021， were included， involving 120 cases of CHB， 340 cases of hepatitis B liver cirrhosis （HBLC）， 64 cases of precancerous lesions with hepatitis B liver cirrhosis （PLHC）， and 147 cases of hepatitis B liver cirrhosis with hepatocellular carcinoma （HCC）. A Survey form of traditional Chinese medicine syndrome during malignant transformation of chronic hepatitis B was designed， and the general information， auxiliary examination and the four examinations results were collected. Factor analysis and K-means clustering were used to determine and statistically analyze the syndrome and syndrome elements. ResultsFive traditional Chinese medicine （TCM） syndrome types were identified in CHB patients， while there were six TCM syndrome types in HBLC， PLHC and HCC stages. Among CHB patients， the main syndromes were liver constraint and spleen deficiency （53.33%） and liver-gallbladder damp-heat （21.67%）， and the dominant syndrome elements were qi stagnation （27.60%）， heat （17.71%） and qi deficiency （17.71%）. In the HBLC stage， the syndromes were mainly blood stasis obstructing the collaterals （23.83%） and liver constraint and spleen deficiency （22.35%）， with dominant syndrome elements being blood stasis （19.25%）， dampness （17.46%）， and qi deficiency （15.01%）. For the PLHC stage， the primary syndrome types were blood stasis obstructing the collaterals （29.68%） and liver-kidney yin deficiency （20.31%）， and the leading syndrome elements were blood stasis （22.12%）， yin deficiency （15.93%）， and qi deficiency （15.04%）. In the HCC stage， the syndrome was dominated by blood stasis obstructing the collaterals （33.34%） and liver-kidney yin deficiency （19.73%）， with the main syndrome elements being blood stasis （24.52%）， yin deficiency （16.09%）， and qi deficiency （15.33%）. During the progression of CHB to malignancy， there was a gradual decrease in excess syndromes including liver-gallbladder damp-heat and water-dampness internal obstruction from 21.67% to 19.04%. In contrast， deficiency syndromes including liver-kidney yin deficiency and spleen-kidney yang deficiency increased from 15.83% to 31.97%. Additionally， excess syndrome elements including qi stagnation， heat and dampness decreased from 59.89% to 34.48%， while deficiency syndrome elements including qi deficiency， yin deficiency and yang deficiency increased from 32.30% to 41.00%. ConclusionDuring the malignant transformation of CHB， there exists a progression of syndrome and syndrome elements， shifting from qi stagnation， heat and qi deficiency to blood stasis （predominantly excess）， dampness and qi deficiency， and then to blood stasis （predominantly deficiency）， yin deficiency and qi deficiency， characterized by “deficiency-excess complex， and shift from excess to deficiency”.

Clinical characteristics and prognosis of 12 cases of lupus nephritis complicated with thrombotic microangiopathy / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical characteristics, pathological features, treatment regimen, and prognosis of children with lupus nephritis (LN) and thrombotic microangiopathy (TMA), as well as the treatment outcome of these children and the clinical and pathological differences between LN children with TMA and those without TMA.@*METHODS@#A retrospective analysis was conducted on 12 children with LN and TMA (TMA group) who were admitted to the Department of Nephrology, Children's Hospital of Nanjing Medical University, from December 2010 to December 2021. Twenty-four LN children without TMA who underwent renal biopsy during the same period were included as the non-TMA group. The two groups were compared in terms of clinical manifestations, laboratory examination results, and pathological results.@*RESULTS@#Among the 12 children with TMA, 8 (67%) had hypertension and 3 (25%) progressed to stage 5 chronic kidney disease. Compared with the non-TMA group, the TMA group had more severe tubulointerstitial damage, a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at onset, and higher cholesterol levels (P<0.05). There were no significant differences between the two groups in the percentage of crescent bodies and the levels of hemoglobin and platelets (P>0.05).@*CONCLUSIONS@#There is a higher proportion of individuals with hypertension among the children with LN and TMA, as well as more severe tubulointerstitial damage. These children have a higher SLEDAI score and a higher cholesterol level.