Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
Epithelial-Mesenchymal Transition/drug effects* ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Humans ; Animals ; Lung Neoplasms/metabolism* ; Chemokines, CC/antagonists & inhibitors* ; Mice ; Mice, Nude ; Drugs, Chinese Herbal/administration & dosage* ; Cell Line, Tumor ; Neoplasm Metastasis ; Tumor-Associated Macrophages/drug effects* ; Mice, Inbred BALB C ; Signal Transduction/drug effects*

Objective To investigate the effect of oral fish oil on wound healing and related indexes in patients with diabetic foot ulcer(DFU).Methods A randomized,double-blind,placebo-controlled design was used to recruit 68 patients with DFU aged 18-80 years old in the hospital,and the baseline clinical data of the patients were collected.The patients were randomly divided into experimental group(32 cases,fish oil soft capsule,3 g/d)and control group(33 cases,corn oil soft capsule,3 g/d)by random number generated by Ex-cel,and the intervention lasted for 12 weeks.The primary endpoints included the proportion of complete wound healing and healing area≥50%.The secondary endpoints included wound area,healing time,inflamma-tion index,glucose metabolism index,nutrition related index and wound reinfection.Additionally,the influen-cing factors of wound healing were analyzed.Results After intervention,the proportion of complete wound healing and healing area≥50%in the experimental group was significantly higher than that in the control group(P=0.007,0.039).In the subjects with complete wound healing,the mean healing time in the experi-mental group was shorter than that in the control group,but the difference was not statistically significant(P=0.132).The reduction area of wound area in the experimental group was significantly larger than that in the control group(P=0.045).The decrease of interleukin(IL)-6 and IL-8 in the experimental group was significantly higher than that in the control group(P<0.05).There was no significant difference in the reduc-tion of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),neutrophil-to-lymphocyte ratio(NLR),glycated hemoglobin A1c(HbA1c)and platelet-to-lymphocyte ratio(PLR)between the two groups(P>0.05).The improvement of prealbumin(PA)in the experimental group was higher than that in the control group,but the difference was not statistically significant(P>0.05).Multivariate logistic regression analysis showed that oral fish oil intervention(OR=6.771,95%CI:1.787-25.652),HbA1c(OR=4.149,95%CI:1.026-16.770)and ulcer type(OR=4.319,95%CI:1.026-18.173)were the influencing factors of wound healing(P<0.05).Conclusion Oral fish oil promotes wound healing in patients with DFU,which may be re-lated to improving the level of chronic inflammation in the body.

Objective:To select and obtain relevant evidence on the prevention and management of gastric retention in premature infants, so as to form the best summary of evidence.Methods:According to the "6S" evidence model system, we searched the domestic and foreign evidence-based databases, relevant guide websites, and association websites for all literature on the prevention and management of gastric retention in premature infants, including clinical decisions, guidelines, best practice information books, evidence summaries, systematic evaluations, and expert consensus. The search period was from January 1, 2013 to June 8, 2023.Results:A total of 12 articles were included, including 5 guidelines, 1 recommended practice, 5 systematic reviews, 1 expert consensuses. A total of 20 pieces of best evidence were collected, mainly involving 6 aspects of feeding management, placement of gastric tube, position management, gastric residue monitoring, gastric residue treatment, intervening measure.Conclusions:This study summarized the best evidence for the prevention and management of gastric retention in premature infants, so as to provide theoretical basis for clinical management of gastric retention and promote the establishment of enteral nutrition in premature infants.

Background Multimorbidity imposes a heavy burden on individuals, families, and society. There are relatively few studies exploring patterns of multimorbidity among middle-aged adults in China. Objective To explore the current status of multimorbidity, associated risk factors, and multimorbidity patterns among adults aged 45-64 years in China, so as to provide a scientific basis to prevent and control multimorbidity in China. Methods A total of 5494 adults aged 45-64 years from the Chinese Health and Nutrition Survey (CHNS) in 2018 were selected. Of these, 2494 (45.39%) were men and 3000 (54.61%) were women. The nine diseases included were hypertension, diabetes, dyslipidaemia, obesity, mild cognitive impairment (MCI), myocardial infarction, stroke, asthma, and tumor. The prevalence of each disease or multimorbidity was expressed as N (%). Comparisons of multimorbidity prevalence between different groups were performed using the χ² test or Cochran-Armitage trend test. Association rule with the Apriori algorithm was used to explore the pattern of multimorbidity, with parameters set at a minimum conditional support of 3.00%, a minimum rule confidence of 50.00%, and a lift of >1.20. Logistic regression was used to evaluate the associations between selected risk factors and multimorbidity. Results In 2018, 37.44% of participants reported multimorbidity in 15 provinces of China. The prevalence of diseases in descending order was dyslipidaemia (39.99%), hypertension (39.48%), obesity (16.42%), MCI (14.47%), diabetes (14.16%), tumor (1.09%), stroke (1.04%), myocardial infarction (0.71%), and asthma (0.64%). A total of seven multimorbidity patterns were identified in this group. Obesity paired with hypertension, and diabetes paired with dyslipidemia were the two major patterns of multimorbidity in the general population and age or sex subgroups. The multimorbidity patterns of different populations were concentrated in the combination of obesity, hypertension, diabetes, and dyslipidemia. The risk of multimorbidity was lower in females than in males (OR=0.85, 95%CI: 0.75, 0.97). The multimorbidity risk was 1.56 times higher in the 55-64 years group than in the 45-54 years group (OR=1.56, 95%CI: 1.40, 1.75). Drinking in the past year increased the risk of multimorbidity by 25% (OR=1.25, 95%CI: 1.08, 1.45) compared to no alcohol comsumption in the past year. High and medium levels of physical activity were associated with a decreased OR (high: OR=0.74, 95%CI: 0.65, 0.85; medium: OR=0.81, 95%CI: 0.70, 0.93) with low level of physical activity as reference. Conclusion In 2018, there was a high prevalence rate of multimorbidity among middle-aged adults in China. The main multimorbidity patterns were obesity-hypertension and diabetes-dyslipidemia. Surveillance and interventions should be strengthened particularly for men, individuals with alcohol consumption or insufficient physical activity, and those with major multimorbidity patterns.

With the world aging aggravation,the prevalence of neurodegenerative diseases has risen year by year,which brings a huge burden on society and family.However,the effective treatment drugs are still scarce,there is an urgent need to discover new therapeutic targets and develop new therapeutic strategies.Recent studies have found that the the mitochondrial calcium uniporter(MCU)has an important function in many neurodegenerative diseases,the imbalance of mitochondrial calcium homeostasis caused by its abnormal expression or function is one of the important mechanisms of neurodegenerative diseases.Inhibiting the MCU function can play the good neuroprotective role,the specific inhibitors of MCU have shown the good prospect in treating various neurodegenerative diseases.This paper sketched the structure,function,regulatory mecha-nism and specific inhibitors of MCU,and focused on analyzing the role of MCU in the occurrence and develop-ment of different neurodegenerative diseases in order to provide reference for further exploration of MCU as a new therapeutic target for neurodegenerative diseases.

OBJECTIVE To systematically evaluate the efficacy and safety of vonoprazan （VPZ） for Helicobacter pylori （Hp） eradication therapy. METHODS Retrieved from The Cochrane Library， Embase， PubMed， CNKI， VIP and Wanfang database， randomized controlled trials about VPZ for Hp eradication therapy （trial group） versus proton pump inhibitor （PPI） （control group） were collected during the inception to July 2022. After data extraction and quality evaluation with bias risk assessment tool recommended by Cochrane System Evaluation Manual 5.1.0， meta-analysis was performed by using RevMan5.3 software. RESULTS Nine studies with 2 134 patients were included. Compared with control group， the overall Hp eradication rate of trial group increased significantly in either the ITT analysis or PP analysis， being 87.5% vs. 76.2% [RR＝1.14， 95%CI （1.06，1.21）， P＜0.001] and 92.4% vs. 80.5% [RR＝1.11， 95%CI （1.03，1.21）， P＜0.01]， respectively. According to ITT and PP analysis of primary treatment subgroup， compared with control group， the overall Hp eradication rate of trial group increased significantly， being 88.4% vs. 76.5% [RR＝1.15， 95%CI （1.09，1.22）， P＜0.000 01] and 92.8% vs. 80.9% [RR＝1.12， 95%CI（1.03，1.23）， P＜ 0.05]； according to ITT and PP analysis of rescue therapy subgroup， there was no significant difference in the overall Hp eradication rate between control group and trial group （P＞0.05）. According to ITT and PP analysis of triple therapy subgroup， compared with control group， overall Hp eradication rate of trial group increased significantly， being 88.3% vs. 75.6% [RR＝1.16， 95%CI （1.08， 1.25）， P＜0.000 1] and 92.6% vs. 77.6% [RR=1.15， 95%CI （1.04， 1.28）， P＜0.01]； according to ITT and PP analysis of quadruple therapy subgroup， there was no significant difference in the overall Hp eradication rate between control group and trial group （P＞0.05）. Compared with control group， the incidence of adverse events in trial group decreased significantly， being 34.2% vs. 40.9% [RR＝0.84， 95%CI（0.70，0.99）， P＜ 0.05]. There was no statistical significance in the incidence of serious adverse events between 2 groups （P＞0.05）. CONCLUSIONS Compared with PPI therapy， the efficacy of VPZ-based triple therapy is better， particularly in primary treatment patients. However， VPZ has no significant advantage in rescue treatment and bismuth-containing quadruple regimen. And the safety and tolerance of VPZ for Hp eradication therapy are well， even better than PPI.

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

The accurate annotation of transcription start sites(TSSs)and their usage are critical for the mechanistic understanding of gene regulation in different biological contexts.To fulfill this,specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner,and various computational tools have also been developed for in silico pre-diction of TSSs solely based on genomic sequences.Most of these computational tools cast the problem as a binary classification task on a balanced dataset,thus resulting in drastic false positive predictions when applied on the genome scale.Here,we present DeeReCT-TSS,a deep learning-based method that is capable of identifying TSSs across the whole genome based on both DNA sequence and conventional RNA sequencing data.We show that by effectively incorporating these two sources of information,DeeReCT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell types.Furthermore,we develop a meta-learning-based extension for simultaneous TSS annotations on 10 cell types,which enables the identification of cell type-specific TSSs.Finally,we demonstrate the high precision of DeeReCT-TSS on two independent datasets by correlating our predicted TSSs with experimentally defined TSS chromatin states.The source code for DeeReCT-TSS is available at https://github.-com/JoshuaChou2018/DeeReCT-TSS_release and https://ngdc.cncb.ac.cn/biocode/tools/BT007316.

Objective:To explore the effect of evidence-based nursing practice on the prevention and management of urinary tract infection in patients with radical prostatectomy.Methods:From January 2019 to December 2020, 106 patients with radical prostatectomy who were admitted to the First Affiliated Hospital of Zhengzhou University were selected as the research object by convenience sampling method. The patients were divided into the observation group (53 cases) and the control group (53 cases) by random number table method. The observation group was given evidence-based nursing for the prevention and management of urinary tract infection, while the control group was given routine nursing. The postoperative urinary tract infection incidence and urethral orifice status were compared between the two groups.Results:The incidence of urinary tract infection in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . The urethral orifice state score of the observation group was lower than that of the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The evidence-based nursing applied in the prevention and management of urinary tract infection in patients with radical prostatectomy has an exact effect, which can effectively prevent urinary tract infection and improve the quality of urethral orifice nursing.