Hepatocellular carcinoma （HCC） is the sixth most common cancer in the world. In recent years， the clinical early diagnosis and treatment protocols of HCC have been improved， whereas the prognosis of patients is still not satisfactory， which is due to the fact that the mechanism of HCC development has not been fully elucidated. Therefore， it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China. Epigenetics has become a research hotspot because of its reversibility and easy regulation. According to relevant studies， HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation， promotion， and progression stages. HCC is categorized as infantile malnutrition with accumulation， hypochondriac pain， tympan ites， and abdominal mass in traditional Chinese medicine （TCM）. In the treatment of HCC， TCM with low toxicity， multi-targets， and multi-mechanisms can inhibit tumor growth， alleviate the clinical symptoms， and enhance the quality of life of the patients. Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation， histone modification， and non-coding RNA. Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development. There are few studies on epigenetic regulation in TCM treatment of HCC， and there is still much room for development in basic and clinical trials. This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism， with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.

Objective To investigate the incidence and risk factors of recurrence of renal calculi after intracavitary lithotripsy. Methods The clinical data of 190 patients with renal stones who underwent endoluminal lithotripsy in our hospital were retrospectively collected. Based on the results of CT, B-ultrasound, or X-ray examination of the urinary system during the 2-year follow-up period, therecurrence of renal calculi was analyzed. Univariate and multivariate Logistic regression were used to analyze the risk factors of stone recurrence. Results of 190 patients, 49 patients experienced stone recurrence within 2 years after surgery, with a recurrence rate of 25.79%. Univariate Logistic regression analysis showed that body mass index(BMI), diabetes, smoking, older age and hypertension were protective factors for stone recurrence. Multivariate Logistic regression analysis showed that diabetes and smoking were risk factors for stone recurrence, while age and hypertension were protective factors for stone recurrence. Conclusion The recurrence of renal stone after intracavitary lithotripsy is common. Diabetes and smoking are risk factors for the recurrence of renal stone, while older age and hypertension are protective factors.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg^-1·d^-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg^-1·d^-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

Objective:To understand the current situation of smartphone addiction and mental health of medical freshmen, and conduct research on the relationship between smartphone addiction and mental health, so as to provide evidence for the prevention and intervention of smartphone addiction among medical freshmen.Methods:A stratified random sampling method was used to select 279 freshmen in the medical profession of Binzhou Medical University as the research objects, and the revised smartphone addiction scale (SAS-C) and mental health symptom self-rating checklist scale (SCL-90) were selected for testing. SPSS 19.0 was used for t test. Results:A percentage of 29.71 medical freshmen had smartphone addiction problems, which was generally above average. The SCL-90 total scores and the scores of somatization, interpersonal sensitivity, depression, anxiety, hostility, psychosis and other factors in the smartphone addiction group were significantly higher than those in non-smartphone addiction group. The total score of smartphone addiction in medical professional freshmen was significantly correlated with the total score of SCL-90. In addition to the interference factors of daily life, other factors had positive correlation with various factors of SCL-90. Interpersonal sensitivity and obsessive-compulsive symptoms had a significant predictive effect on smartphone addiction (β=0.24, 0.26, P < 0.01), which were important variables affecting mobile phone addiction of medical freshmen. Conclusion:Many medical freshmen have the problem of smartphone addiction, which may cause a series of psychological problems, especially obsessive-compulsive symptoms, interpersonal sensitivity, anxiety and psychosis.

Objective:To evaluate the efficacy of modular flexible ureteroscopy combined with minimally invasive percutaneous nephrolithotomy in patients with complex kidney stones.Methods:From March 2017 to February 2019 in Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Hebei Province, 150 patients with complex kidney stones were selected. The patients were divided into group A, group B and group C by sortition method with 50 cases each. Group A was treated with modular flexible ureteroscopy, group B was treated with standard percutaneous nephrolithotomy, and group C was treated with modular flexible ureteroscopy combined with minimally invasive percutaneous nephrolithotomy. The operation time, transoperative bleeding, hospitalization time, calculi clearance 1- and 3-month after operation, procalcitonin (PCT) and C-reactive protein (CRP) 2 h before operation and 1 and 3 d after operation were compared among 3 groups.Results:The operation time, transoperative bleeding and hospitalization time in group C were significantly lower than those in group A and group B: (65.25 ± 7.90) min vs. (99.73 ± 8.52) and (96.11 ± 9.92) min, (33.22 ± 3.70) ml vs. (41.54 ± 3.62) and (45.17 ± 3.30) ml, (3.90 ± 0.90) d vs. (4.77 ± 1.17) and (5.70 ± 1.19) d, the calculi clearance 1- and 3-month after operation was significantly higher than that in group A and group B: 94.00% (47/50) vs. 80.00% (40/50) and 82.00% (41/50), 98.00% (49/50) vs. 84.00% (42/50) and 86.00% (43/50), and there were statistical differences ( P<0.05). There were no statistical differences in PCT and CRP 2 h before operation among 3 groups ( P>0.05); the PCT and CRP 1 and 3 d after operation in group C were significantly lower than those in group A and group B, and there were statistical differences ( P<0.05). There were no statistical differences in all indexes between group A and group B ( P>0.05). Conclusions:Modular flexible ureteroscopy combined with minimally invasive percutaneous nephrolithotomy can effectively improve calculi clearance, reduce surgical trauma, shorten operation time, promote recovery, and have significant therapeutic effects in the treatment of complex kidney stones.

Objective:To explore the compression stability in left common iliac vein (LCIV) at different times by contrast-enhanced CT in the same patients.Methods:This retrospective study included 124 patients (without signs of lower extremity venous diseases),who underwent contrast-enhanced CT at pelvic cavity and reexamined within one year.The degree of compression changes in LCIV was calculated and compared between the two examinations.Moreover,the relationship between age and the compression rate of LCIV was analyzed.Results:In the two examinations for the same patient,the compression rate of LCIV was almost the same,and there was no significant difference (t=-0.957,P＞0.05).Moreover,the compression rate of LCIV did not significantly change between different gender (P＞0.05).No matter whether the compression rate was more than 50％,there was no significant difference in the rate of LCIV compression between two examinations (P＞0.05).There was no significant correlation between age and the compression rate of LCIV (age＜50 years:r=0.152,P＞0.05;age ≥ 50 years:r=-0.214,P＞0.05).Conclusion:The compression degree of LCIV is almost stable,which is not significantly correlated with the age.The contrast-enhanced CT for single time can accurately display and diagnose the compression degree of LCIV.