Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

DEGENERATED LEMMA (DEL) regulates lemma development and affects rice grain yield.

In grass, the lemma is a unique floral organ structure that directly determines grain size and yield. Despite a great deal of research on grain enlargement caused by changes in glume cells, the importance of normal development of the glume for normal grain development has been poorly studied. In this study, we investigated a rice spikelet mutant, degenerated lemma (del), which developed florets with a slightly degenerated or rod-like lemma. More importantly, del also showed a significant reduction in grain length and width, seed setting rate, and 1000-grain weight, which led to a reduction in yield. The results indicate that the mutation of the DEL gene further affects rice grain yield. Map-based cloning shows a single-nucleotide substitution from T to A within Os01g0527600/DEL/OsRDR6, causing an amino acid mutation of Leu-34 to His-34 in the del mutant. Compared with the wild type, the expression of DEL in del was significantly reduced, which might be caused by single base substitution. In addition, the expression level of tasiR-ARF in del was lower than that of the wild type. RT-qPCR results show that the expression of some floral organ identity genes was changed, which indicates that the DEL gene regulates lemma development by modulating the expression of these genes. The present results suggest that the normal expression of DEL is necessary for the formation of lemma and the normal development of grain morphology and therefore has an important effect on the yield. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01297-6.

SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron.

The coronavirus nucleocapsid (N) protein is known to bind to nucleic acids and facilitate viral genome encapsulation. Here we report that the N protein can mediate RNA or DNA entering neighboring cells through ACE2-independent, receptor (STEAP2)-mediated endocytosis, and achieve gene expression. The effect is more pronounced for the N protein of wild-type SARS-CoV-2 than that of the Omicron variant and other human coronaviruses. This effect is enhanced by RANTES (CCL5), a chemokine induced by N protein, and lactate, a metabolite produced in hypoxia, to cause more damage. These findings might explain the clinical observations in SARS-CoV-2-infected cases. Moreover, the N protein-mediated function can be inhibited by N protein-specific monoclonal antibodies or p38 mitogen-activated protein kinase inhibitors. Since the N-protein-mediated nucleic acid endocytosis involves a receptor commonly expressed in many types of cells, our findings suggest that N protein may have an additional role in SARS-CoV-2 pathogenesis.

lncRNA-disease association prediction based on the weight matrix and projection score.

With the development of medical science, long noncoding RNA (lncRNA), originally considered as a noise gene, has been found to participate in a variety of biological activities. Several recent studies have shown the involvement of lncRNA in various human diseases, such as gastric cancer, prostate cancer, lung cancer, and so forth. However, obtaining lncRNA-disease relationship only through biological experiments not only costs manpower and material resources but also gains little. Therefore, developing effective computational models for predicting lncRNA-disease association relationship is extremely important. This study aimed to propose an lncRNA-disease association prediction model based on the weight matrix and projection score (LDAP-WMPS). The model used the relatively perfect lncRNA-miRNA relationship data and miRNA-disease relationship data to predict the lncRNA-disease relationship. The integrated lncRNA similarity matrix and the integrated disease similarity matrix were established by fusing various methods to calculate the similarity between lncRNA and disease. This study improved the existing weight algorithm, applied it to the lncRNA-miRNA-disease triple network, and thus proposed a new lncRNA-disease weight matrix calculation method. Combined with the improved projection algorithm, the lncRNA-miRNA relationship and miRNA-disease relationship were used to predict the lncRNA-disease relationship. The simulation results showed that under the Leave-One-Out-Cross-Validation framework, the area under the receiver operating characteristic curve of LDAP-WMPS could reach 0.8822, which was better than the latest result. Taking adenocarcinoma and colorectal cancer as examples, the LDAP-WMPS model was found to effectively infer the lncRNA-disease relationship. The simulation results showed good prediction performance of the LDAP-WMPS model, which was an important supplement to the research of lncRNA-disease association prediction without lncRNA-disease relationship data.

Active components and molecular mechanism of Syringa oblata Lindl. in the treatment of endometritis based on pharmacology network prediction.

Antibiotic treatment of endometritis was limited by the inevitable antibiotic residues and risk of bacterial resistance. Therefore, the development of safe and effective strategies for endometritis treatment is urgently needed. Syringa oblata Lindl. (SOL) showed great pharmacological potential against endometritis. However, the active components and underlying mechanism of SOL for endometritis treatment remain indeterminate. In our study, the active components and possible molecular mechanism of SOL against endometritis were predicted through computer data mining and biological networks construction. It was predicted that the main active components of SOL were luteolin, kaempferol, oleanolic acid, and rutin, and their anti-endometritis effect was mainly attributed to the TLRs/NF-κB signaling pathway. Furthermore, a green and efficient deep eutectic solvent combined with ultrasound-assisted extraction (DES-UAE) was performed and optimized to obtain high contents of total flavonoid, rutin, and luteolin. The four predicted active components in the SOL extracts were qualitatively and quantitatively analyzed by LC/MS and HPLC. Finally, the pharmacological effects of SOL and active components have been verified by Staphylococcus aureus-endometritis models in mice. H&E staining and bacterial load in uterus tissues assays initially validated the pharmacodynamic effects of SOL, and quantitative real-time PCR (RT-qPCR) and ELISA results confirmed that SOL and four active components could ameliorate the uterus injury caused by Staphylococcus aureus, the mechanism of action is related to the TLRs/NF-κB signaling pathway.

Patient-Derived Organoid Serves as a Platform for Personalized Chemotherapy in Advanced Colorectal Cancer Patients.

Background: Addition of oxaliplatin to adjuvant 5-FU has significantly improved the disease-free survival and served as the first line adjuvant chemotherapy in advanced colorectal cancer (CRC) patients. However, a fraction of patients remains refractory to oxaliplatin-based treatment. It is urgent to establish a preclinical platform to predict the responsiveness toward oxaliplatin in CRC patients as well as to improve the efficacy in the resistant patients. Methods: A living biobank of organoid lines were established from advanced CRC patients. Oxaliplatin sensitivity was assessed in patient-derived tumor organoids (PDOs) in vitro and in PDO-xenografted tumors in mice. Based on in vitro oxaliplatin IC50 values, PDOs were classified into either oxaliplatin-resistant (OR) or oxaliplatin-sensitive (OS) PDOs. The outcomes of patients undergone oxaliplatin-based treatment was followed. RNA-sequencing and bioinformatics tools were performed for molecular profiling of OR and OS PDOs. Oxaliplatin response signatures were submitted to Connectivity Map algorithm to identify perturbagens that may antagonize oxaliplatin resistance. Results: Oxaliplatin sensitivity in PDOs was shown to correlate to oxaliplatin-mediated inhibition on PDO xenograft tumors in mice, and parallelled clinical outcomes of CRC patients who received FOLFOX treatment. Molecular profiling of transcriptomes revealed oxaliplatin-resistant and -sensitive PDOs as two separate entities, each being characterized with distinct hallmarks and gene sets. Using Leave-One-Out Cross Validation algorithm and Logistic Regression model, 18 gene signatures were identified as predictive biomarkers for oxaliplatin response. Candidate drugs identified by oxaliplatin response signature-based strategies, including inhibitors targeting c-ABL and Notch pathway, DNA/RNA synthesis inhibitors, and HDAC inhibitors, were demonstrated to potently and effectively increase oxaliplatin sensitivity in the resistant PDOs. Conclusions: PDOs are useful in informing decision-making on oxaliplatin-based chemotherapy and in designing personalized chemotherapy in CRC patients.

Ultrasound-assisted deep eutectic solvents extraction of glabridin and isoliquiritigenin from Glycyrrhiza glabra: Optimization, extraction mechanism and in vitro bioactivities.

Licorice (Glycyrrhiza glabra) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.

Structural break-aware pairs trading strategy using deep reinforcement learning.

Pairs trading is an effective statistical arbitrage strategy considering the spread of paired stocks in a stable cointegration relationship. Nevertheless, rapid market changes may break the relationship (namely structural break), which further leads to tremendous loss in intraday trading. In this paper, we design a two-phase pairs trading strategy optimization framework, namely structural break-aware pairs trading strategy (SAPT), by leveraging machine learning techniques. Phase one is a hybrid model extracting frequency- and time-domain features to detect structural breaks. Phase two optimizes pairs trading strategy by sensing important risks, including structural breaks and market-closing risks, with a novel reinforcement learning model. In addition, the transaction cost is factored in a cost-aware objective to avoid significant reduction of profitability. Through large-scale experiments in real Taiwan stock market datasets, SAPT outperforms the state-of-the-art strategies by at least 456% and 934% in terms of profit and Sortino ratio, respectively.

Association of signal transducer and activator of transcription 3 and signal transducer and activator of transcription 5 with regulatory T cell/T helper 17 cell balance in chronic hepatitis B / 临床肝胆病杂志

The immune mechanism of chronic hepatitis B (CHB) persistent infection is closely associated with T cells, and the development of T cells requires the coordination of a variety of cytokines. The proteins of the signal transducer and activator of transcription (STAT) family are mainly involved in the signal transduction of cytokines, and STAT5a/b and STAT3 play an important role in the differentiation and development of regulatory T cells (Treg) and T helper 17 cells (Th17). This article analyzes the association of STAT3 and STAT5 with Treg/Th17 balance in CHB and investigates the chronicity of hepatitis B virus infection and the regulatory mechanism of liver inflammation.

Effect of spinal manipulation therapy on chronic nonspecific neck pain: a meta-analysis / 中国康复理论与实践

@#Objective To evaluate the effects of spinal manipulation therapy (SMT) on chronic nonspecific neck pain (CNSNP) by using World Health Organization Family International Classifications (WHO-FICs). Methods Randomized controlled trials (RCTs) about the effects of SMT on CNSNP were searched from PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, CBM and CNKI from database establishment to December 31st, 2021. At least two researchers extracted the data. Cochrane bias risk assessment tool and Physiotherapy Evidence Database Scale were used to evaluate the quality of the included articles. Revman 5.4 software and Stata 16.0 software were used for meta-analyses and publication bias analysis respectively. Results A total of 15 RCTs that represented 1 067 participants were evaluated. In terms of body functions, compared with the control group, SMT significantly reduced Visual Analog Score for pain (MD = -0.85, 95%CI -1.06 to -0.63, P < 0.00001) and Numerical Rating Scale (MD = -0.92, 95%CI -1.29 to -0.55, P < 0.001), increased pressure pain thresholds (SMD = 0.67, 95%CI 0.47 to 0.86, P < 0.001), cervical range of motion (ROM) of flexion/extension (SMD = 0.51, 95%CI 0.33 to 0.68, P < 0.001) and rotation (SMD = 0.20, 95%CI 0.01 to 0.38, P = 0.04), improved root mean square of cervical muscles electromygraphy (MD = 2.17, 95%CI 0.06 to 4.29, P = 0.04), but not significantly in cervical ROM of lateral flexion (SMD = 0.19, 95%CI -0.00 to 0.38, P = 0.06), cervical strength (SMD = -0.18, 95%CI -0.84 to 0.49, P = 0.60) and endurance (SMD = 0.18, 95%CI -0.39 to 0.75, P = 0.53). In term of activities and participation, SMT significantly improved cervical disability (MD = -0.96, 95%CI -1.55 to -0.38, P = 0.001), but not significantly in health status of patients with CNSNP (SMD = 0.08, 95%CI -0.03 to 0.20, P = 0.15). Conclusion SMT could improve pain intensity, pain sensitivity, cervical ROM and disability in patients with CNSNP, but its efficacy on muscle function, proprioception and health status is unclear.

Screening of the ubiquitin-proteasome system activators for anti-Alzheimer's disease by the high-content fluorescence imaging system / 中国天然药物

Ubiquitin-proteasome system (UPS) plays an important role in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The discovery of UPS activators for anti-neurodegenerative diseases is becoming increasingly important. In this study, we aimed to identify potential UPS activators using the high-throughput screening method with the high-content fluorescence imaging system and validate the neuroprotective effect in the cell models of AD. At first, stable YFP-CL1 HT22 cells were successfully constructed by transfecting the YFP-CL1 plasmid into HT22 cells, together with G418 screening. The degradation activity of the test compounds via UPS was monitored by detecting the YFP fluorescence intensity reflected by the ubiquitin-proteasome degradation signal CL1. By employing the high-content fluorescence imaging system, together with stable YFP-CL1 HT22 cells, the UPS activators were successfully screened from our established TCM library. The representative images were captured and analyzed, and quantification of the YFP fluorescence intensity was performed by flow cytometry. Then, the neuroprotective effect of the UPS activators was investigated in pEGFP-N1-APP (APP), pRK5-EGFP-Tau P301L (Tau P301L), or pRK5-EGFP-Tau (Tau) transiently transfected HT22 cells using fluorescence imaging, flow cytometry, and Western blot. In conclusion, our study established a high-content fluorescence imaging system coupled with stable YFP-CL1 HT22 cells for the high-throughput screening of the UPS activators. Three compounds, namely salvianolic acid A (SAA), salvianolic acid B (SAB), and ellagic acid (EA), were identified to significantly decrease YFP fluorescence intensity, which suggested that these three compounds are UPS activators. The identified UPS activators were demonstrated to clear AD-related proteins, including APP, Tau, and Tau P301L. Therefore, these findings provide a novel insight into the discovery and development of anti-AD drugs.

A case of acute carbon monoxide poisoning with secondary intestinal obstruction and thrombosis / 中华劳动卫生职业病杂志

Acute carbon monoxide poisoning can cause multiple organ damage due to hypoxia. In severe cases, it can be life-threatening and has a high fatality rate. Intestinal obstruction and thrombosis are rare complications of carbon monoxide poisoning. A case of carbon monoxide poisoning was reported. In addition to the central nervous system lesion, intestinal obstruction and lower limb thrombosis were also found. In the treatment of carbon monoxide poisoning patients, the clinician was able to treat the common complications, attention should be paid to gastrointestinal tract, thrombotic disease and other rare complications, so as to avoid missed diagnosis.

Identification of COVID-19 B-cell epitopes with phage-displayed peptide library.

BACKGROUND: Coronavirus disease 19 (COVID-19) first appeared in the city of Wuhan, in the Hubei province of China. Since its emergence, the COVID-19-causing virus, SARS-CoV-2, has been rapidly transmitted around the globe, overwhelming the medical care systems in many countries and leading to more than 3.3 million deaths. Identification of immunological epitopes on the virus would be highly useful for the development of diagnostic tools and vaccines that will be critical to limiting further spread of COVID-19. METHODS: To find disease-specific B-cell epitopes that correspond to or mimic natural epitopes, we used phage display technology to determine the targets of specific antibodies present in the sera of immune-responsive COVID-19 patients. Enzyme-linked immunosorbent assays were further applied to assess competitive antibody binding and serological detection. VaxiJen, BepiPred-2.0 and DiscoTope 2.0 were utilized for B-cell epitope prediction. PyMOL was used for protein structural analysis. RESULTS: 36 enriched peptides were identified by biopanning with antibodies from two COVID-19 patients; the peptides 4 motifs with consensus residues corresponding to two potential B-cell epitopes on SARS-CoV-2 viral proteins. The putative epitopes and hit peptides were then synthesized for validation by competitive antibody binding and serological detection. CONCLUSIONS: The identified B-cell epitopes on SARS-CoV-2 may aid investigations into COVID-19 pathogenesis and facilitate the development of epitope-based serological diagnostics and vaccines.

A feasibility study of the application of structural similarity index to the assessment of radiotherapy plan quality / 中华放射医学与防护杂志

Objective:To assess the three-dimensional dose distribution in radiotherapy plans using the structural similarity index(SSIM), compare the performance of SSIM with commonly used quality assessment indices, and develop a SSIM-based quality assessment method of multiple prescribed doses.Methods:The SSIM was introduced to providea quality score of various voxels by comparing actual and ideal three-dimensional dose data and combining the spatial location information of the voxels. Then the average value in a region of interest (ROI) was calculated as the quality score of the region. Fifty-three cases of cervical cancer were selected to analyze the correlation of the SSIM with the uniformity index (HI), conformity index (CI) of the dose distribution in various ROIs and to explore the capability of the SSIM to reflect the uniformity and conformity of dose distribution.Two types of quality defects were individually introduced into two of 53 radiotherapy plans. Then the two plans were compared with normal plans to characterize the response of the SSIM.Results:There was no correlation between HI and SSIM in positive lymph nodes(PGTVnd) due to the decrease in the HI sensitivity, while there was a significant negative correlation between them in regions where PGTVnd was removed from the planning target volume(PTV, R=-0.86, P<0.01). Meanwhile, there was a significant positive correlation between CI and SSIM in PGTVnd ( R=0.83, P<0.01). Therefore, the SSIM can be used to identify the artificial design defects in plans by determining abnormal dose gradients. Conclusions:Apart from reducing the defects of previous assessment parameters, the SSIM has the capability to assess the quality of radiotherapy plans by combining the uniformity and conformity of dose distribution and can provide accurate feedback on the spatial locations of quality defects.

Preliminary study on gut microbiota prediction of radiation enteritis in patients with cervical and endometrial cancers / 中华放射医学与防护杂志

Objective:To explore the relationships between the gut microbiota in patients with cervical and endometrial cancers and the severity of radiation enteritis they suffered during radiotherapy.Methods:Feces samples were collected from 37 patients with cervical or endometrial cancer who received radical radiotherapy (RR) and postoperative radiotherapy (PR). Symptoms were recorded according to the grades of diarrhea and proctitis stated in CTCAE 5.0. The grade of symptoms was considered a high grade (HG) in the case of ≥ 2 and a low grade (LG). The 16S rRNA sequencing technology was used for DNA analysis of the samples.Results:The α diversity of gut microbiota was significantly higher in patients with LG symptoms (LG group) than that in patients with HG symptoms (HG group, P<0.05) and the β diversity also differed between the two groups (stress<0.2) before radiotherapy. Meanwhile, the Ruminococcus gnavus was significantly higher in the HG group than that in the LG group before radiotherapy ( P<0.05), and thus it may serve as a biomarker for the prediction of the severity of radiation enteritis in the patients before radiotherapy. The gut microbiota in the LG and HG groups showed different changes after three weeks of radiotherapy. In addition, RR patients showed higher gut microbiota diversity and less severe radiation enteritis than PR patients. Meanwhile, Faecalibacterium prausnitzii was significantly higher in RR patients than that in PR patients before radiotherapy ( P<0.05), which may correlate negatively with radiation toxicity. Conclusions:The characteristics of gut microbiota in patients with cervical and endometrial cancers were closely related to the severity of radiation enteritis they suffered during radiotherapy. Furthermore, prior treatment such as surgery might reduce radiation tolerance of the patients.

Effect of therapeutic communication system intervention mode combined with staged rehabilitation on postoperative curative effect and quality of life of patients with cardiac valve / 中国实用护理杂志

Objective:To explore and analyze the effect of therapeutic communication system (TCS) intervention mode on Therapeutic effect and quality of life in patients with cardiac valve replacement.Methods:A total of 103 patients with cardiac valve replacement admitted from February 2018 to February 2019 were selected and divided into observation group (51 cases) and control group (52 cases) according to the random number table method. Patients in the control group were treated with staged rehabilitation intervention, while patients in the observation group were treated with staged rehabilitation combined with TCS intervention mode. Patients' prognosis, the score of Short Form 36-item Health Survey (SF-36) before and after intervention, the changes in the score of the Morisky label Scale (MMAS-8) before and after intervention, and perioperative indicators were recorded and compared between the two groups.Results:The quality of life scores of the observation group at 1 month,3 months and 6 months after intervention were (64.42±9.51), (76.23±9.19), (87.24±9.21) points, which were significantly higher than (58.73±9.38), (61.23±9.29), (76.29±9.42) points of the control group ( t values were 3.057, 8.237, 5.964, P<0.05);and also higher than those before intervention (54.29±9.14, 54.45± 9.31), the difference was statistically significant ( F values were 11.358, 7.581, P<0.001); the ICU hospitalization time (43.25±1.72),bed rest time (42.13±8.32) and hospitalization time (16.32±4.20) days in the observation group were significantly lower than (54.34±1.93), (72.33±8.54), (21.24±4.36) days in the control group, and the difference was statistically significant ( t values were 30.766, 18.174, 5.831, P<0.001); the drug compliance (7.21±0.17) was significantly higher than that of the control group (6.01±0.34) ( t value was 22.588, P<0.001). Conclusion:Stage rehabilitation combined with TCS intervention mode can effectively improve the prognosis and perioperative indicators of patients with heart valve, and improve the quality of life of patients, which is worthy of clinical application.

Role of T helper 17 cell/regulatory T cell imbalance in the progression of HBV-related liver diseases / 临床肝胆病杂志

Patients with chronic hepatitis B (CHB) often have immune-mediated liver injury, and it is considered that the interaction between viral infection and immune response is an important cause of disease progression. CHB can progress to liver fibrosis, liver cirrhosis, and even hepatocellular carcinoma (HCC). This article reviews the discovery of T helper 17 (Th17) cells and regulatory T (Treg) cells, describes their own features, and elaborates on their role and mechanism of action in maintaining the stability of the immune system. This article also analyzes the role of Th17/Treg cell imbalance in CHB, liver fibrosis, liver cirrhosis, and HCC and points out that Th17/Treg cell imbalance may promote the aggravation of HBV-related liver diseases.

Role of the JAK/STAT/SOCS signaling pathway in hepatitis B virus-related liver diseases / 临床肝胆病杂志

The JAK/STAT/SOCS signaling pathway can mediate a variety of cytokines involved in inflammation, tumor, and autoimmune diseases and it also plays an important role in hepatitis B virus (HBV) infection-related liver diseases. This article briefly reviews the structure and signal pathway regulation of JAK-STAT and SOCS and elaborates on their role in the development and progression of HBV-related chronic hepatitis B, liver cirrhosis, liver failure, and hepatocellular carcinoma. The final analysis shows that the JAK/STAT/SOCS signaling pathway is dysregulated in HBV-related liver disease and is involved in the development and progression of the disease, and it may even influence the treatment and prognosis of the disease.

Combined Effect of Smoking and Obesity on Coronary Heart Disease Mortality in Male Veterans: A 30-year Cohort Study / 生物医学与环境科学（英文）

Objective@#Evidence is lacking regarding the combined effects of smoking and obesity on mortality from coronary heart disease in male veterans. This study aimed to explore the combined effect of smoking and obesity on coronary heart disease mortality in male veterans in China.@*Methods@#A cohort of 1,268 male veterans from 22 veteran centers in Xi'an (Shaanxi Province, China) were followed up once every 2 years from February 1, 1987 to October 30, 2016. The endpoint was death from any cause. The hazard ratio ( @*Results@#The total follow-up was 24394.21 person-years; each subject was followed up for a mean duration of 19.24 years. By the end of the study, of the 1,268 veterans, 889 had died, 363 were alive, and 16 were lost to follow-up. Cox regression analysis results revealed that current smoking ( @*Conclusion@#Our results suggest that obese veterans who smoke might be an important target population for coronary heart disease mortality control.

Noninvasive diagnostic models for chronic hepatitis B liver fibrosis / 临床肝胆病杂志

Hepatitis B virus (HBV) infection is still a public problem that seriously threatens human health. Evaluation of liver fibrosis progression with an efficient noninvasive model is of great significance for condition assessment, disease management, and prognostic evaluation in patients with chronic HBV infection. This article reviews the noninvasive models commonly used in the diagnosis of liver fibrosis in recent years, summarizes the research background, methods, related studies, and advantages and disadvantages of these models, and analyzes the current research status and possible development trends of liver fibrosis assessment models. Recent studies have shown that although current models are not perfect for Chinese patients with chronic HBV infection as the main predisposing factor for liver fibrosis, the excellent performance of noninvasive models in liver fibrosis assessment provides a reference for the assessment of liver fibrosis in patients with chronic HBV infection and can replace liver biopsy to a certain extent.