Oncogenic and immunological role of EDIL3 in human tumours: From pan-cancer analysis to validation in gastric cancer.

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan-Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.

CLEC4D as a Novel Prognostic Marker Boosts the Proliferation and Migration of Gastric Cancer via the NF-κB/AKT Signaling Pathway.

Purpose: The functions of C-type lectin domain family 4 member D (CLEC4D), one member of the C-type lectin/C-type lectin-like domain superfamily, in immunity have been well described, but its roles in cancer biology remain largely unknown. Patients and Methods: This study aims to explore the role of CLEC4D in gastric cancer (GC). Bioinformatics preliminarily analyzed the expression of CLEC4D in gastric cancer. Immunohistochemical staining was used to detect the expression level and clinical pathological characteristics of CLEC4D in gastric cancer. The biological function of CLEC4D in gastric cancer cell lines was verified through in vitro and in vivo experiments. Results: In this study, CLEC4D expression was found to be markedly increased in gastric cancer (GC) tissues compared with matched normal gastric tissues, and high CLEC4D expression independently predicted unfavorable overall survival in patients with GC. Knockdown of CLEC4D markedly inhibited GC cell proliferation and migration. Mechanistically, CLEC4D knockdown deactivated the Akt and NF-κB signaling pathways in GC cells. Conclusion: Together, these results demonstrate that aberrantly increased CLEC4D expression promotes cancer phenotypes via the Akt and NF-κB signaling pathways in GC cells.

Addressing the influencing path of social noise exposure risk perception on noise mitigation behavior.

Noise interference has become a common health risk in population-densified urban areas where social noise occurs frequently. However, the influence of an individual's perception of social noise exposure risk on reactive behavior remains unknown. This study developed an integrative psychosocial perspective-based model that includes constructs from two theoretical frameworks (the Theory of Planned Behavior and the Value-Belief-Norm theory) to analyze noise risk perception and behavioral intention for social noise mitigation. Haidian District, Beijing, was selected as the case study area and 300 questionnaires were distributed. The results showed that personal attributes had significant effects on residents' noise exposure risk perception and noise-mitigation behavioral intentions. Noise perception, as represented by awareness of consequences and ascription of responsibility, was significantly related to noise mitigation behavioral intention. Awareness of consequences directly positively influenced behavioral intention (ß = 0.235, p < 0.001) and indirectly positively influenced behavioral intention through the mediating effect of the ascription of responsibility, which accounted for 24 % of the total effect of awareness of consequences on behavioral intention. This study provides valuable insights into the risks of social noise and encourages adaptive measures to reduce it.

Telomere-to-telomere assembly of cassava genome reveals the evolution of cassava and divergence of allelic expression.

Cassava is a crucial crop that makes a significant contribution to ensuring human food security. However, high-quality telomere-to-telomere cassava genomes have not been available up to now, which has restricted the progress of haploid molecular breeding for cassava. In this study, we constructed two nearly complete haploid resolved genomes and an integrated, telomere-to-telomere gap-free reference genome of an excellent cassava variety, 'Xinxuan 048', thereby providing a new high-quality genomic resource. Furthermore, the evolutionary history of several species within the Euphorbiaceae family was revealed. Through comparative analysis of haploid genomes, it was found that two haploid genomes had extensive differences in linear structure, transcriptome features, and epigenetic characteristics. Genes located within the highly divergent regions and differentially expressed alleles are enriched in the functions of auxin response and the starch synthesis pathway. The high heterozygosity of cassava 'Xinxuan 048' leads to rapid trait segregation in the first selfed generation. This study provides a theoretical basis and genomic resource for molecular breeding of cassava haploids.

Case Report: sintilimab-induced Stevens-Johnson Syndrome in a patient with advanced lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have been widely applicated in clinical therapy in recent years. Skin-related adverse reaction is one of the most common adverse events for ICIs. Stevens-Johnson syndrome (SJS) is one of the serious cutaneous reactions threatening the life. Here, we reported a case of 76-year-old male patient with poorly differentiated metastatic lung adenocarcinoma, after 9 weeks exposure of sintilimab (3 doses) combined with paclitaxel liposome after concurrent chemotherapy/radiotherapy, experienced Stevens-Johnson syndrome involving limbs, trunk, lip and the oral mucosa. Biopsy of the skin tissue showed infiltration of CD4 and CD8 positive T lymphocytes. We also found PD-L1 expression in the glands and the basal layer of the skin. This finding is distinct from the previously reported expression of PD-L1 on the surface of epidermal keratinocytes in patients with SJS due to immunotherapy.

EDIL3 is a potential prognostic biomarker that correlates with immune infiltrates in gastric cancer.

Background: EDIL3, which contains epidermal growth factor-like repeats and discoidin I-like domains, is a secretory protein that plays an important role in embryonic development and various illnesses. However, the biological function of EDIL3 in gastric cancer (GC) is still unclear. The objective of this research was to explore the role and potential mechanism of EDIL3 in GC. Methods: In this study, we used the GEPIA, HPA, MethSurv, SMART, STRING, GeneMANIA, LinkedOmics TIMER, TIMER2.0, TISIDB, and RNAactDrug databases to comprehensively analyze the roles of EDIL3 in GC. To validate the in silico findings, EDIL3 expression was measured in our collected GC tissues. Meanwhile, several in vitro experiments were performed to test the function of EDIL3 in GC. Results: We found that EDIL3 was highly expressed in GC and associated with adverse clinical features. In vitro assays revealed that EDIL3 promoted the proliferation, migration, and invasion of GC cells. The functions of EDIL3 and co-expression genes were significantly associated with extracellular structure organization and matrix receptor interaction. EDIL3 expression was positively associated with numerous tumor-infiltrating immune cells and their biomarkers. Conclusion: This study determined that EDIL3 may function as an oncogene and is associated with immune infiltration in GC. EDIL3 could be used as a potential therapeutic target for GC.

Graph-based pan-genomes: increased opportunities in plant genomics.

Due to the development of sequencing technology and the great reduction in sequencing costs, an increasing number of plant genomes have been assembled, and numerous genomes have revealed large amounts of variations. However, a single reference genome does not allow the exploration of species diversity, and therefore the concept of pan-genome was developed. A pan-genome is a collection of all sequences available for a species, including a large number of consensus sequences, large structural variations, and small variations including single nucleotide polymorphisms and insertions/deletions. A simple linear pan-genome does not allow these structural variations to be intuitively characterized, so graph-based pan-genomes have been developed. These pan-genomes store sequence and structural variation information in the form of nodes and paths to store and display species variation information in a more intuitive manner. The key role of graph-based pan-genomes is to expand the coordinate system of the linear reference genome to accommodate more regions of genetic diversity. Here, we review the origin and development of graph-based pan-genomes, explore their application in plant research, and further highlight the application of graph-based pan-genomes for future plant breeding.

Research Progress on Risk Factors and Intervention Measures for Prolonged Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation --Review / 中国实验血液学杂志

Prolonged thrombocytopenia (PT) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with an incidence of about 5%-37%, which is closely related to the poor prognosis of patients. Previous studies have shown that transplantation type, CD34+ cell number, pretreatment regimen, acute graft-versus-host disease, virus infection, pre-transplantation serum ferritin level and donor specific antibodies can affect platelet implantation after transplantation. Identifying the risk factors of PT is helpful to early identify high-risk patients and take targeted preventive measures according to different risk factors to reduce the incidence of PT, reduce the risk of bleeding and improve the prognosis of patients. This article reviews the latest research progress of risk factors and intervention measures related to PT after allo-HSCT, in order to provide reference for the prevention and treatment of PT after transplantation.

Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer / 中华胃肠外科杂志

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

Research Progress of Chimeric Antigen Receptor Modified NK Cells in the Treatment of Acute Myeloid Leukemia --Review / 中国实验血液学杂志

Chimeric Antigen Receptor (CAR) is a research hotspot in the field of cellular immunotherapy in recent years, and CAR-T cells therapy are developing rapidly in hematological malignant tumors, but their clinical application is still limited by related risks. It is particularly important to find more optimized immunoreactive cells. Natural killer (NK) cells, as key effector cells of innate immunity, can kill tumor or infected cells quickly without prior sensitization. Autologous or allogeneic NK cell infusion has become an effective cell therapy for acute myeloid leukemia (AML). CAR-NK cells combine the advantages of CAR targeting tumor specific antigens and enhancing immune cells activity with the innate antitumor function of NK cells to enhance the targeting and lytic activity of NK cells to AML primordial cells. At present, most of the CAR-NK treatments for AML are still in the stage of specific target screening and verification. This article reviews the latest research progress of CAR-NK cell therapy in the field of AML therapy.

Evaluating smoking cessation service at an emergency department clinical observation unit.

OBJECTIVES: To evaluate the effectiveness of a pilot smoking cessation service in an emergency department (ED) clinical observation unit. STUDY DESIGN: A descriptive case series review was undertaken of smoking cessation service patients in the short-stay unit of an acute hospital in Singapore from July 1, 2018, to December 31, 2019. METHODS: Upon admission, ED nurses screen all patients regarding their current smoking status and implement the 5 A's framework, which involves the steps of Ask-Advise-Assess-Assist-Arrange. Patients in the "contemplation" and "preparation" stages were offered the following components: (1) a bedside counseling session by a pharmacist and (2) a follow-up appointment at an outpatient smoking cessation clinic. Postdischarge follow-up telephone calls at 1, 6, and 12 months were carried out as part of the study data collection to obtain abstinence information. RESULTS: Forty-seven patients were included in the study; the majority were male (n = 41; 87.2%). The median numbers of cigarettes smoked per day at baseline, 1 month, 6 months, and 12 months were 14, 5, 3, and 5, respectively. The overall point-prevalence abstinence rates over the same follow-up time points were 26.5%, 38.7%, and 31.3%, respectively. The proportions of patients lost to follow-up at 1 month, 6 months, and 12 months were 27.7%, 34.0%, and 31.9%, respectively. CONCLUSIONS: Given the small sample and high number of uncontactable patients, more research is needed to assess whether the trend toward increasing point-prevalence abstinence rate over time and the trend toward decreasing median number of cigarettes smoked are observed in a larger sample.

In vitro and in vivo Evaluation of the Bioactive Nanofibers-Encapsulated Benzalkonium Bromide for Accelerating Wound Repair with MRSA Skin Infection.

Purpose: Developing the ideal drug or dressing is a serious challenge to controlling the occurrence of antibacterial infection during wound healing. Thus, it is important to prepare novel nanofibers for a wound dressing that can control bacterial infections. In our study, the novel self-assembled nanofibers of benzalkonium bromide with bioactive peptide materials of IKVAV and RGD were designed and fabricated. Methods: Different drug concentration effects of encapsulation efficacy, swelling ratio and strength were determined. Its release profile in simulated wound fluid and its cytotoxicity were studied in vitro. Importantly, the antibacterial efficacy, inhibition of biofilm formation effect and wound healing against MRSA infections in vitro and in vivo were performed after observing the tissue toxicity in vivo. Results: It was found that the optimized drug load (0.8%) was affected by the encapsulation efficacy, swelling ratio, and strength. In addition, the novel nanofibers with average diameter (222.0 nm) and stabile zeta potential (-11.2 mV) have good morphology and characteristics. It has a delayed released profile in the simulated wound fluid and good biocompatibility with L929 cells and most tissues. Importantly, the nanofibers were shown to improve antibacterial efficacy, inhibit biofilm formation, and lead to accelerated wound healing following infection with methicillin-resistant Staphylococcus aureus. Conclusion: These data suggest that novel nanofibers could effectively shorten the wound-healing time by inhibiting biofilm formation, which make it promising candidates for treatment of MRSA-induced wound infections.

The Cold-Adapted, Temperature-Sensitive SARS-CoV-2 Strain TS11 Is Attenuated in Syrian Hamsters and a Candidate Attenuated Vaccine.

Live attenuated vaccines (LAVs) replicate in the respiratory/oral mucosa, mimic natural infection, and can induce mucosal and systemic immune responses to the full repertoire of SARS-CoV-2 structural/nonstructural proteins. Generally, LAVs produce broader and more durable protection than current COVID-19 vaccines. We generated a temperature-sensitive (TS) SARS-CoV-2 mutant TS11 via cold-adaptation of the WA1 strain in Vero E6 cells. TS11 replicated at >4 Log10-higher titers at 32 °C than at 39 °C. TS11 has multiple mutations, including those in nsp3, a 12-amino acid-deletion spanning the furin cleavage site of the S protein and a 371-nucleotide-deletion spanning the ORF7b-ORF8 genes. We tested the pathogenicity and protective efficacy of TS11 against challenge with a heterologous virulent SARS-CoV-2 D614G strain 14B in Syrian hamsters. Hamsters were randomly assigned to mock immunization-challenge (Mock-C) and TS11 immunization-challenge (TS11-C) groups. Like the mock group, TS11-vaccinated hamsters did not show any clinical signs and continuously gained body weight. TS11 replicated well in the nasal cavity but poorly in the lungs and caused only mild lesions in the lungs. After challenge, hamsters in the Mock-C group lost weight. In contrast, the animals in the TS11-C group continued gaining weight. The virus titers in the nasal turbinates and lungs of the TS11-C group were significantly lower than those in the Mock-C group, confirming the protective effects of TS11 immunization of hamsters. Histopathological examination demonstrated that animals in the Mock-C group had severe pulmonary lesions and large amounts of viral antigens in the lungs post-challenge; however, the TS11-C group had minimal pathological changes and few viral antigen-positive cells. In summary, the TS11 mutant was attenuated and induced protection against disease after a heterologous SARS-CoV-2 challenge in Syrian hamsters.

Inhibition of TAK1 aggravates airway inflammation by increasing RIPK1 activity and promoting macrophage death in a mouse model of toluene diisocyanate-induced asthma / 南方医科大学学报

OBJECTIVE@#To explore the effect of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice.@*METHODS@#Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated.@*RESULTS@#TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05).@*CONCLUSION@#Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.

Wastewater SARS-CoV-2 monitoring as a community-level COVID-19 trend tracker and variants in Ohio, United States.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 129 million confirm cases. Many health authorities around the world have implemented wastewater-based epidemiology as a rapid and complementary tool for the COVID-19 surveillance system and more recently for variants of concern emergence tracking. In this study, three SARS-CoV-2 target genes (N1 and N2 gene regions, and E gene) were quantified from wastewater influent samples (n = 250) obtained from the capital city and 7 other cities in various size in central Ohio from July 2020 to January 2021. To determine human-specific fecal strength in wastewater samples more accurately, two human fecal viruses (PMMoV and crAssphage) were quantified to normalize the SARS-CoV-2 gene concentrations in wastewater. To estimate the trend of new case numbers from SARS-CoV-2 gene levels, different statistical models were built and evaluated. From the longitudinal data, SARS-CoV-2 gene concentrations in wastewater strongly correlated with daily new confirmed COVID-19 cases (average Spearman's r = 0.70, p < 0.05), with the N2 gene region being the best predictor of the trend of confirmed cases. Moreover, average daily case numbers can help reduce the noise and variation from the clinical data. Among the models tested, the quadratic polynomial model performed best in correlating and predicting COVID-19 cases from the wastewater surveillance data, which can be used to track the effectiveness of vaccination in the later stage of the pandemic. Interestingly, neither of the normalization methods using PMMoV or crAssphage significantly enhanced the correlation with new case numbers, nor improved the estimation models. Viral sequencing showed that shifts in strain-defining variants of SARS-CoV-2 in wastewater samples matched those in clinical isolates from the same time periods. The findings from this study support that wastewater surveillance is effective in COVID-19 trend tracking and provide sentinel warning of variant emergence and transmission within various types of communities.

Mechanism of total C-21 steroidal glucosides from root of Cynanchum auriculatum in activation of human hepatic stellate cells via TGF-β / 中国药理学通报

Aim To investigate the inhibitory effect of total C-21 steroidal glucosides (TCSG) from the root of Cynanchum auriculatum on activation of human hepatic stellate cells and the underlying mechanism. Methods The fibrosis model in vitro was established by treating LX-2 cells with TGF-β

Progress in understanding hepatic fibrosis and renal fibrosis based on the gut-liver-kidney axis / 药学学报

Fibrosis is a pathological process of abnormal hyperplasia and excessive deposition of extracellular matrix during the process of repair after tissue and organ damage. Injury/inflammation caused by variously chronic diseases is a major trigger for fibrogenesis. Fibrosis of the liver and kidney is a common organ fibrosis. Recently, the intestinal microbiota has been shown to be extensively involved in the development of liver and kidney diseases, which may follow from changes in the intestinal microbial composition and intestinal integrity. This promotes the development of liver and/or kidney fibrosis through endocrine, cell signaling and other pathways. This paper reviews the research progress in understanding liver fibrosis and kidney fibrosis based on the gut-liver-kidney axis, which may be helpful for providing new strategies and theoretical basis for the diagnosis and treatment of hepatic and renal fibrosis.

Effect of C21 steroidal glycoside of Cynanchum auriculatum on liver and kidney fibrosis through TLR4 pathway / 中国中药杂志

The liver and kidney fibrosis model was established by thioacetamide(TAA) and unilateral ureteral obstruction(UUO) in SD rats. The rats were randomly divided into three groups: model group, low and high-dose groups of C21 steroidal glycosides of Cynanchum auriculatum. Another blank control group was set. Four weeks later, serum was taken to detect the biochemical indexes of liver and kidney function. Urine protein and urine creatinine were detected by kits. Liver and kidney tissue samples were stained with HE and Masson staining, and hydroxyproline content was detected. Western blot was used to detect expressions of fibrotic proteins, inflammatory factors and TLR4 signaling pathways, so as to observe the preventive and therapeutic effects of C21 steroidal glycosides from C. auriculatum on hepatic and renal fibrosis and explore its molecular mechanism. Four weeks later, serum biochemical results showed that liver and kidney functions were seriously damaged, and pathological sections showed that inflammatory cell infiltration, decrease of parenchymal cells, and increase of interstitial fibrosis in liver and kidney tissues. The results showed that low and high doses(150, 300 mg·kg~(-1)) of C21 steroidal glycosides could significantly reduce the collagen deposition and the pathological changes of liver and kidney fibrosis compared with the model group. At the same time, we found that the expression levels of TLR4 and MyD88 signaling pathway proteins were significantly increased in the liver and kidney tissues of the model group, and a large number of NF-κB signaling pathway proteins migrated into the nucleus. On the contrary, the expression levels of TLR4, MyD88 signaling pathway proteins and the nuclear migration of NF-κB were significantly inhibited in the low and high dose groups of C21 steroidal glycosides from C. auriculatum. Therefore, it was speculated that the mechanism of C21 steroidal glycoside for preventive and therapeutic effect on hepatic and renal fibrosis was related to inhibit TLR4/MYD88/NF-κB inflammatory pathway, thus preventing hepatic and renal fibrosis.

Detection of Pathogenic Isoforms of IKZF1 in Leukemic Cell Lines and Acute Lymphoblastic Leukemia Samples: Identification of a Novel Truncated IKZF1 Transcript in SUP-B15.

Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and a subset of BCR-ABL1-like ALL. Infantile and childhood ALL that express these pathogenic IKZF1 isoforms have shown inferior clinical outcomes and can be resistant to tyrosine kinase inhibitors. Using ALL cell lines, we designed and validated a method to detect abnormal IKZF1 transcripts. In the SUP-B15 leukemia cell line, we noted novel IKZF1 transcripts that include both an Ik-6 splice and a transcript with a 14 base pair insertion at the C-terminus. There was also increased IKZF2 protein in SUP-B15 as compared to other ALL lines. Expression of Ik-6 could be suppressed by treatment with the pro-apoptotic type II histone deacetylase inhibitor givinostat. In 17 adult ALL samples, we noted the Ik-6 isoforms in 6 of 15 BCR-ABL1-, and 1 of 2 BCR-ABL1+ cases, with Ik-8 also expressed in one case. Cases with Ik-6 expression showed inferior survival as well as older age at presentation, lower expression of CD10 and more commonly a diploid karyotype.

[Overview of "tian-yin-yang" acupuncture, an acupuncture school of Huang's Zhuang medicine of Guangxi].

The theory of "tian-yin-yang" of Zhuang medicine was explored and the academic achievements and experience of professor HUANG Jin-ming were summarized to explain the theory and clinical characteristics of tian-yin-yang acupuncture, an acupuncture school of Huang 's Zhuang medicine of Guangxi. This acupuncture method is guided by the theory of "three-qi synchronization" and "tian-yin-yang" of Zhuang medicine, based on the theory of "three channels and two paths", with regulating qi as the method and regulating spirit as the basis. After the patient is calmed and resting, the micro needle shallow needling technique is adopted, mainly at the umbilical ring point, so as to achieve the purpose of regulating the mind and treating the root cause.