Association between serum ferritin and bone turnover marker levels in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease.

OBJECTIVE: To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), ß-I type collagen carboxy-terminal peptide (ß-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed. RESULTS: Compared with the T2DM+non-HF group, ß-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, ß-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with ß-CTx [ß = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [ß=-0.108; 95%CI (-0.006, -0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between ß-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith ß-CTx [ß = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [ß=-0.124; 95% CI (0.007,0.001) and ß=-0.168; 95% CI (-0.012, -0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [ß=-0.117; 95% CI (-0.007, -0.001) and ß=-0.003; 95% CI (-0.013, -0.003)]. CONCLUSION: SF level was positively correlated with ß-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.

Self-assembly of peptide nanomaterials at biointerfaces: molecular design and biomedical applications.

Self-assembly is an important strategy for constructing ordered structures and complex functions in nature. Based on this, people can imitate nature and artificially construct functional materials with novel structures through the supermolecular self-assembly pathway of biological interfaces. Among the many assembly units, peptide molecular self-assembly has received widespread attention in recent years. In this review, we introduce the interactions (hydrophobic interaction, hydrogen bond, and electrostatic interaction) between peptide nanomaterials and biological interfaces, summarizing the latest advancements in multifunctional self-assembling peptide materials. We systematically demonstrate the assembly mechanisms of peptides at biological interfaces, such as proteins and cell membranes, while highlighting their application potential and challenges in fields like drug delivery, antibacterial strategies, and cancer therapy.

Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos.

Base editors have substantial promise in basic research and as therapeutic agents for the correction of pathogenic mutations. The development of adenine transversion editors has posed a particular challenge. Here we report a class of base editors that enable efficient adenine transversion, including precise A•T-to-C•G editing. We found that a fusion of mouse alkyladenine DNA glycosylase (mAAG) with nickase Cas9 and deaminase TadA-8e catalyzed adenosine transversion in specific sequence contexts. Laboratory evolution of mAAG significantly increased A-to-C/T conversion efficiency up to 73% and expanded the targeting scope. Further engineering yielded adenine-to-cytosine base editors (ACBEs), including a high-accuracy ACBE-Q variant, that precisely install A-to-C transversions with minimal Cas9-independent off-targeting effects. ACBEs mediated high-efficiency installation or correction of five pathogenic mutations in mouse embryos and human cell lines. Founder mice showed 44-56% average A-to-C edits and allelic frequencies of up to 100%. Adenosine transversion editors substantially expand the capabilities and possible applications of base editing technology.

Rules of Chinese Herbal Intervention of Radiation Pneumonia Based on Network Pharmacology and Data Mining.

Objective: To explore the mechanism and principles of traditional Chinese medicine (TCM) in the management of radiation pneumonia. Methods: The targets of radiation pneumonia were obtained by screening the GeneCards, OMIM, TTD, DrugBank, and HERB databases, analyzing ADME parameters. In addition, compounds and Chinese herbs that can act on the targets were screened from the TCMSP database. The core target compounds for TCM were used to construct the target-compound, compound-traditional Chinese medicine, and target-compound-traditional Chinese medicine networks. These networks were further used to select the core targets, compounds, and TCM. The binding strength between the core targets and compounds was determined using AutoDock Vina. The trajectory for the molecular dynamics simulation was completed by Desmond version 2020. Results: A total of 55 active targets in radiation pneumonia were identified. Subsequently, 137 candidate compounds and 469 Chinese herbs were matched. Frequency statistics showed that the Chinese herbs that could interfere with radiation pneumonia were mainly bitter, spicy, and sweet, with both cold and warm properties. Moreover, they mainly belonged to liver and lung channels. The core targets included TNF, IL-6, TGF-ß1, and TP53. The most important components were quercetin, resveratrol, and (-)-epigallocatechin-3-gallate. Moreover, the most significant traditional Chinese herbs were Perilla pueraria, ephedra, Lonicerae japonicae, and sea buckthorn. Furthermore, analysis of 222 sets of receptor-ligand docking results suggested that the compounds had good docking activity to their core targets. By combining the docking binding energy, we determined that the chemical compounds had strong binding energy to the targets. Conclusion: Using network pharmacology, we explored the potential mechanism of TCM in the treatment of radiation pneumonia. The general rules for application of TCM in the treatment of radiation pneumonia were summarized. This study provides baseline information for future research on the development of TCM for the management of radiation pneumonia.

Effect of postmastectomy radiotherapy on pT1-2N1 breast cancer patients with different molecular subtypes.

OBJECTIVE: To clarify the effect of postmastectomy radiotherapy (PMRT) on pT1-2N1 breast cancer patients with different molecular subtypes. METHODS: We retrospectively analyzed the data of 5442 patients with pT1-2N1 breast cancer treated using modified radical mastectomy in 11 hospitals in China. Univariate, multivariate, and propensity score matching (PSM) analyses were used to evaluate the effect of PMRT on locoregional recurrence (LRR). RESULTS: With a median follow-up duration of 63.8 months, the 5-year LRR rates were 4.0% and 7.7% among patients treated with and without PMRT, respectively (p < 0.001). PMRT was independently associated with reduced LRR after adjustments for confounders (p < 0.001). After grouping the patients according to the molecular subtype of cancer and conducting PSM, we found that the 5-year LRR rates among patients treated with and without PMRT (in that order) were as follows: luminal HER2-negative cancer, 1.9% and 6.5% (p < 0.001); luminal HER2-positive cancer, 3.8% and 13.7% (p = 0.041); HER2-overexpressing cancer, 10.2% and 15.5% (p = 0.236); and triple-negative cancer, 4.6% and 15.9% (p = 0.002). Among patients with HER2-overexpressing and triple-negative cancers, the LRR hazard rate displayed a dominant early peak, and was extremely low after 5 years. However, patients with luminal cancer continued to have a long-lasting high annual LRR hazard rate during follow-up. CONCLUSION: PMRT significantly reduced the LRR risk in patients with pT1-2N1 luminal and triple-negative breast cancers, but had no effect on the LRR risk in patients with HER2-overexpressing cancer. Patients with different molecular subtypes displayed different annual LRR patterns, and the late recurrence of the luminal subtype suggests the necessity of long-term follow-up to evaluate the efficacy of PMRT.

Exploring the Biological Mechanism of Huang Yam in Treating Tumors and Preventing Antitumor Drug-Induced Cardiotoxicity Using Network Pharmacology and Molecular Docking Technology.

Drugs for the treatment of tumors could result in cardiotoxicity and cardiovascular diseases. We aimed to explore the anticancer properties of Huang yam as well as its cardioprotective properties using network pharmacology and molecular docking technology. The cardiovascular targets of the major chemical components of Huang yam were obtained from the following databases: TCMSP, ETCM, and BATMAN-TCM. The active ingredients of Huang yam were obtained from SwissADME. The cardiovascular targets of antitumor drugs were obtained using GeneCards, OMIM, DrugBank, DisGeNET, and SwissTargetPrediction databases. The drug-disease intersection genes were used to construct a drug-compound-target network using Cytoscape 3.7.1. A protein-protein interaction network was constructed using Cytoscape's BisoGenet, and the core targets of Huang yam were screened to determine their antitumor properties and identify the cardiovascular targets based on topological parameters. Potential targets were imported into the Metascape platform for GO and KEGG analysis. The results were saved and visualized using R software. The components with higher median values in the network were molecularly docked with the core targets. The network contained 10 compounds, including daucosterol, delusive, dioxin, panthogenin-B, and 124 targets, such as TP53, RPS27A, and UBC. The GO function enrichment analysis showed that there were 478 items in total. KEGG enrichment analysis showed a total of 140 main pathways associated with abnormal transcription of cancer, PI3K-Akt signaling pathway, cell cycle, cancer pathway, ubiquitination-mediated proteolysis, and other pathways. Molecular docking results showed that daucosterol, delusive, dioxin, and panthogenin-B had the highest affinity for TP53, RPS27A, and UBC. The treatment of diseases using traditional Chinese medicine encompasses multiple active ingredients, targets, and pathways. Huang yam has the potential to treat cardiotoxicity caused by antitumor drugs.

The Use of Traditional Chinese Medicine in Relieving EGFR-TKI-Associated Diarrhea Based on Network Pharmacology and Data Mining.

In this study, the role of traditional Chinese medicine (TCM) in relieving epidermal growth factor receptor-tyrosine kinase inhibitor- (EGFR-TKI-) associated diarrhea was discussed by network pharmacology and data mining. Prediction of drug targets by introducing the EGFR-TKI molecular structures into the SwissTargetPrediction platform and diarrhea-related targets in the DrugBank, GeneCards, DisGeNET, and OMIM databases were obtained. Compounds in the drug-disease target intersection were screened by absorption, distribution, metabolism, and excretion parameters and Lipinski's rule in Traditional Chinese Medicine Systems Pharmacology. TCM-containing compounds were selected, and information on the property, taste, and meridian tropism of these TCMs was summarized and analyzed. A target-compound-TCM network diagram was constructed, and core targets, compounds, and TCMs were selected. The core targets and components were docked by AutoDock Vina (Version 1.1.2) to explore the target combinations of related compounds and evaluate the docking activity of related targets and compounds. Twenty-three potential therapeutic TCM targets for the treatment of EGFR-TKI-related diarrhea were obtained. There were 339 compounds acting on potential therapeutic targets, involving a total of 402 TCMs. The results of molecular docking showed good binding between the core targets and compounds, and the binding between the core targets and compounds was similar to that of the core target and the recommended drug loperamide. TCMs have multitarget characteristics and are present in a variety of compounds used for relieving EGFR-TKI-associated diarrhea. Antitumor activity and the efficacy of alleviating diarrhea are the pharmacological basis of combining TCMs with EGFR-TKI in the treatment of non-small-cell lung cancer. The core targets, compounds, and TCMs can provide data to support experimental and clinical studies on the relief of EGFR-TKI-associated diarrhea in the future.

Study on Medication Rules of Traditional Chinese Medicine against Antineoplastic Drug-Induced Cardiotoxicity Based on Network Pharmacology and Data Mining.

METHODS: The targets of antineoplastic drugs with cardiotoxicity were obtained from the National Center for Biotechnology Information (NCBI) database, China national knowledge infrastructure (CNKI) database, and Swiss Target Prediction platform. Then, the cardiotoxicity-related targets were derived from the Gene Cards, Disgenet, OMIM, and DrugBank databases, as well as the drug of current clinical guidelines. The targets both in these two sets were regarded as potential targets to alleviate ADIC. Then, candidate compounds and herbs were matched via Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. Cytoscape3.7.1 was used to set up the target-compound-herb network. Molecular docking between core targets and compounds was performed with AutodockVina1.1.2. The rules of herbs were summarized by analyzing their property, flavor, and channel tropism. RESULTS: Twenty-one potential targets, 332 candidate compounds, and 400 kinds of herbs were obtained. Five core targets including potassium voltage-gated channel subfamily H member 2 (KCNH2), cyclin-dependent kinase 1 (CDK1), matrix metalloproteinase 2 (MMP2), mitogen-activated protein kinase1 (MAPK1), and tumor protein p53 (TP53) and 29 core compounds (beta-sitosterol, quercetin, kaempferol, etc.) were collected. Five core herbs (Yanhusuo, Gouteng, Huangbai, Lianqiao, and Gancao) were identified. Also, the TCM against ADIC were mainly bitter and acrid in taste, warm in property, and distributed to the liver and lung meridians. CONCLUSION: TCM against ADIC has great potential. Our study provides a new method and ideas for clinical applications of integrated Chinese and western medicine in treating ADIC.

Practicality and short-term outcomes of intracorporeal gastroduodenostomy in totally laparoscopic distal gastrectomy for gastric cancer: A single-centre retrospective study.

OBJECTIVE: Totally laparoscopic distal gastrectomy (TLDG) with intracorporeal anastomosis is feasible because of improved approaches to laparoscopic surgery and the availability of a variety of surgical instruments. This study was designed to evaluate the practicality, safety and short-term operative outcomes of intracorporeal gastroduodenostomy in TLDG for gastric cancer. MATERIALS AND METHODS: Medical records of patients with primary distal gastric cancer undergoing Billroth I (B-I) (n = 37) or B-II anastomosis (n = 41) in TLDG from February 2010 to November 2015 were retrospectively analysed. Perioperative data including the extent of lymph node dissection, number of stapler cartridges used, time required to create the anastomosis, operative time, estimated blood loss, proximal and distal margin length, and number of lymph nodes harvested were collected. Short-term post-operative outcomes evaluated during the initial 30 days after surgery included time to first flatus and earliest liquid consumption, length of post-operative hospital stay and incidence of post-operative complications. RESULTS: B-I anastomosis was mainly applied to patients with carcinoma in the lower third of the gastric body (B-I, 81.08% vs. B-II, 31.71%;P < 0.001). Mean operating (B-I, 153.57 ± 18.25 min vs. B-II, 120.17 ± 11.74 min;P = 0.004) and anastomosis (B-I, 31.92 ± 6.10 min vs. B-II, 25.29 ± 3.84 min;P = 0.01) times were significantly longer for B-I anastomosis compared to B-II anastomosis. There were no significant differences in the number of stapler cartridges used, estimated blood loss, time to first flatus and liquid consumption, length of hospital stay or incidence of complications between these groups. CONCLUSIONS: TLDG with B-I or B-II anastomosis is safe and feasible for gastric cancer. B-II anastomosis may require less time than B-I anastomosis.

Clinical Evaluation and Gait Characteristics before and after Total Knee Arthroplasty Based on a Portable Gait Analyzer.

OBJECTIVE: To evaluate the effects of surgery and rehabilitation on patients undergoing total knee arthroplasty (TKA). METHODS: Twelve patients and 12 healthy controls were enrolled and their clinical scores evaluated by a doctor. Gait data, including walking velocity, stride length, single support time, foot fall and swing power, were collected using a portable gait analyzer from 12 patients before and 6 weeks and 6 months after surgery and from 12 healthy controls. The gait data and clinical scores at selected time points were compared and correlations between gait characteristics and clinical scores assessed. RESULTS: Clinical knee and knee function scores increased significantly from before surgery to 6 weeks to 6 months after surgery (P < 0.001). The only significant differences identified were for single support time on the diseased side between before surgery and 6 months after surgery (P = 0.031) and for foot fall with the diseased side between 6 weeks and 6 months after surgery (P = 0.016). Foot fall and speed of the healthy or diseased sides were significantly different in patients at all time points from those of the healthy subjects (P < 0.05). Single support time on the diseased side was significantly different 6 months after surgery (P = 0.035) in patients than in healthy controls. Single support time on the healthy side before surgery was significantly different from that of healthy controls (P = 0.048) and 6 weeks after surgery (P = 0.042). Stride lengths differed significantly between patients and healthy subjects before surgery (healthy side: P = 0.007; diseased side: P = 0.008) and 6 weeks after surgery (healthy side: P = 0.001; diseased side: P = 0.001), but were not different at 6 months after surgery (healthy side: P = 0.088; diseased side: P = 0.077). The only significant correlations identified were between single support time with the diseased side of patients and their knee (r = 0.43, P = 0.032) and knee function scores (r = 0.493, P = 0.012). CONCLUSIONS: A portable gait analyzer appears to be suitable for evaluating the effects of TKA. Single support time on the diseased side may be a sensitive quantitative index for determining the effect of TKA and rehabilitation.