[Comparative study of different methods of blood purification treatment of paraquat intoxication].

OBJECTIVE: To investigate the different effect of three methods of blood purification for paraquat poisoning patients:hemoperfusion (HP), hemoperfusion combined with hemodialysis (HP + HD), hemoperfusion combined with continuous veno-venous hemofiltration (HP + CVVH). METHODS: 72 cases of paraquat poisoning patients were divided into three groups after giving conventional therapy HP group, HP + HD group, HP + CVVH group. Compared the rate of decline concentrations of paraquat in blood, the liver and the kidney damage between before and after blood purification and contrast the mortality in three groups after different method of blood purification. RESULTS: The rate of decline concentrations of paraquat in blood of the HP + HD group and HP + CVVH group were both significantly greater than the HP group, but this result of HP + HD group has no significant difference compared with HP + CVVH group; Among the three groups of patients after 72 hours, the degree of dysfunction of liver of the HP + HD group and HP + CVVH group were both significantly lower than the HP group, whilely the degree of dysfunction of kidney of the HP + HD group was significantly lower than the HP group and the HP + CVVH group. The survival time of the HP + HD group and the HP + CVVH group were significant linger than the HP group, but the comparison among the three groups had no significant difference in mortality. CONCLUSION: Three blood purification methods can effectively remove paraquat absorbed into the blood, and the hemoperfusion combined with hemodialysis or continuous veno-venous hemofiltration can effectively reduce the degree of damage of liver and kidney and also can prolong survival time, but did not significantly improve the survival rate of patients.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Zuo Jin Wan Reverses the Resistance of Colorectal Cancer to Oxaliplatin by Regulating the MALAT1/miR-200s/JNK Signaling Pathway.

Background: Oxaliplatin (L-OHP) is a common chemotherapy drug used in the treatment of colorectal cancer (CRC). Our previous work showed that Zuo Jin Wan (ZJW), a traditional Chinese medicine prescription, could improve sensitivity to L-OHP in the treatment of CRC, but the detailed mechanism is not clear. In previous mechanistic studies, we found that the miR-200s expression in CRC is associated with L-OHP sensitivity through regulation of MDR1/p-gp and the downstream c-JunN-terminal kinase (JNK) signaling pathway. Moreover, lncRNA-MALAT1 offers great potential in the regulation of drug resistance by interacting with miR-200s. Therefore, in this work, we explored whether ZJW could reverse L-OHP resistance in CRC by regulating MALAT1, miR-200s, and the downstream signaling pathway. Methods: Cell Counting Kit-8 and flow cytometry were used to detect the effects of ZJW combined with L-OHP on chemotherapy tolerance and cell apoptosis of HCT116/L-OHP cells. Western blotting and quantitative real-time PCR (qRT-PCR) were used to detect the activation of the JNK signaling pathway and the protein and mRNA expression levels of the drug resistance-related MDR1/ABCB1 gene in HCT116/L-OHP cells treated with ZJW. The binding sites of MALAT1 and miR-200s were predicted by bioinformatics tools and confirmed by qRT-PCR. qRT-PCR was used to detect the expression of miR-200s and MALAT1 in HCT116/L-OHP cells treated with ZJW. A xenograft model of CRC in nude mice was established to observe the effect of ZJW combined with L-OHP on the growth of subcutaneously transplanted tumors. Apoptosis in tumor cells was detected by TUNEL staining. The activation of the JNK signaling pathway and the expression of drug resistance-related proteins were detected by immunohistochemistry and immunofluorescence. qRT-PCR was used to detect the expression of miR-200s and the MALAT1 gene in the tumors. Results: Our study showed that ZJW could significantly decrease the proliferation and promote apoptosis of HCT116/L-OHP cells treated with L-OHP. We further proved that ZJW could reverse the drug resistance of HCT116/L-OHP cells by reducing MALAT1, indirectly upregulating miR-200s, alleviating the activation of the JNK signaling axis, and downregulating the expression of resistance proteins such as MDR1/ABCB1 and ABCG2. ZJW combined with L-OHP inhibited the growth of subcutaneously transplanted tumors and induced apoptosis in nude mice. ZJW reduced the expression of MALAT1 and upregulated the expression of miR-200s in transplanted tumors. In addition, ZJW also alleviated the activation of the JNK signaling pathway while reducing the expression of MDR1/ABCB1 and ABCG2. Conclusions: Our study identified that MALAT1 promotes colorectal cancer resistance to oxaliplatin by reducing the miR-200s expression. ZJW may reverse chemoresistance by inhibiting the expression of MALAT1 and regulating the miR-200s/JNK pathway, providing an experimental basis for the clinical application of ZJW in relieving chemotherapy resistance.

YYFZBJS inhibits colorectal tumorigenesis by remodeling gut microbiota and influence on M2 macrophage polarization in vivo and in vitro.

Our previous studies indicated that the extract of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) had potent anticancer activities by significantly inhibiting intestinal tumor development in ApcMin/+ mice. However, knowledge regarding the mechanism and effect of YYFZBJS in the prevention of colorectal cancer is limited. In this study, we aim to investigate the preventive effects of YYFZBJS in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. First, the colonic tissues of the AOM/DSS mouse models were collected for biomedical analysis, and gut microbiota profiling was detected post YYFZBJS treatment using a 16S rRNA gene sequencing. Then, antibiotic solution (Abx) mice were acclimated with AOM/DSS treatment and then fed with ETBF with or without YYFZBJS for three cycles. As expected, the intragastric administration of YYFZBJS in the AOM/DSS mouse model significantly decreased the tumor load, the severity of disease activity index (DAI) scores, and the level of M2 macrophage markers such as CD206, Arg-1 and IL-10. Notably, the reverse of polarized macrophages induced by YYFZBJS could suppress CRC cell proliferation and infiltration, as demonstrated by the decrease of some tumor proliferation-related proteins in a dose-dependent manner. Importantly, ETBF dysbiosis can contribute to colon tumor development by stimulating p-STAT3 mediated M2 macrophages polarization to promote chronic inflammation and adenoma malignant transformation, which YYFZBJS can effectively limit. Altogether, we demonstrate that ETBF dysbiosis may contribute to M2 macrophages-promoted colon carcinogenesis and progression of CRC cells, while YYFZBJS could be a promising protective agent against ETBF-mediated colorectal cancer.

Unveiling differentially expressed genes upon regulation of transcription factors in sepsis.

In this study, we integrated the gene expression data of sepsis to reveal more precise genome-wide expression signature to shed light on the pathological mechanism of sepsis. Differentially expressed genes via integrating five microarray datasets from the Gene Expression Omnibus database were obtained. The gene function and involved pathways of differentially expressed genes (DEGs) were detected by GeneCodis3. Transcription factors (TFs) targeting top 20 dysregulated DEGs (including up- and downregulated genes) were found based on the TRANSFAC. A total of 1339 DEGs were detected including 788 upregulated and 551 downregulated genes. These genes were mostly involved in DNA-dependent transcription regulation, blood coagulation, and innate immune response, pathogenic escherichia coli infection, epithelial cell signaling in helicobacter pylori infection, and chemokine signaling pathway. TFs bioinformatic analysis of 20 DEGs generated 374 pairs of TF-target gene involving 47 TFs. At last, we found that five top ten upregulated DEGs (S100A8, S100A9, S100A12, PGLYRP1 and MMP9) and three downregulated DEGs (ZNF84, CYB561A3 and BST1) were under the regulation of three hub TFs of Pax-4, POU2F1, and Nkx2-5. The identified eight DEGs may be regarded as the diagnosis marker and drug target for sepsis.

Evaluation of an Association of Blood Homocysteine Levels With Gastric Cancer Risk From 27 Case-Control Studies.

High blood homocysteine levels may risk gastric cancer. However, observational studies have been plagued by chance, bias, confounding, or reverse causality. In this study, we assessed the relationship between blood homocysteine levels and gastric cancer by using a Mendelian randomization method, which is independent of nongenetic confounding.We took 2 steps to perform Mendelian randomization analysis. First, we evaluated the methylenetetrahydrofolate reductase (MTHFR) C677T association with gastric cancer by a meta-analysis of case-control studies including 7566 patients with gastric cancer and 10 640 control subjects from 27 Case-Control studies. Second, MTHFR C677T polymorphism, which affects the blood homocysteine levels, was used as an instrumental variable to calculate the risk and estimate the association of gastric cancer with this single nucleotide polymorphism (SNP). We obtained an estimate to the association of blood total homocysteine levels with this SNP from a meta-analysis of Genome-Wide Association Studies (GWAS), which comprises a total of 44 147 individuals.In our Mendelian randomization analysis, we demonstrated a significant effect of the blood homocysteine levels on gastric cancer risk, representing an OR of 2.56 (95% CI = 2.41-2.72; P = 5.0×10) for gastric cancer per 1-SD increase in the natural log-transformed blood total homocysteine levels.We proved that there is a causal relationship between blood total homocysteine and risk of gastric cancer, and this study will add insight into the treatment and pathology research of gastric cancer.

Severity and prognosis of acute organophosphorus pesticide poisoning are indicated by C-reactive protein and copeptin levels and APACHE II score.

The aim of the present study was to investigate the plasma levels of C-reactive protein (CRP) and copeptin, in addition to the acute physiology and chronic health evaluation II (APACHE II) scores, in patients with acute organophosphorus pesticide poisoning (AOPP). A total of 100 patients with AOPP were included and divided into mild, moderate and severe groups according to AOPP diagnosis and classification standards. Blood samples were collected from all patients on days 1, 3 and 7 following AOPP. The concentrations of CRP and copeptin in the plasma were determined using enzyme-linked immunosorbent assay. All AOPP patients underwent APACHE II scoring and the diagnostic value of these scores was analyzed using receiver operating characteristic curves (ROCs). On days 1, 3 and 7 after AOPP, the levels of CRP and copeptin were increased in correlation with the increase in AOPP severity, and were significantly higher compared with the control groups. Furthermore, elevated CRP and copeptin plasma levels were detected in patients with severe AOPP on day 7, whereas these levels were reduced in patients with mild or moderate AOPP. APACHE II scores, blood lactate level, acetylcholine esterase level, twitch disappearance time, reactivating agent dose and inability to raise the head were the high-risk factors that affected the prognosis of AOPP. Patients with plasma CRP and copeptin levels higher than median values had worse prognoses. The areas under curve for ROCs were 0.89, 0.75 and 0.72 for CRP levels, copeptin levels and APACHE II scores, respectively. In addition, the plasma contents of CRP and copeptin are increased according to the severity of AOPP. Therefore, the results of the present study suggest that CRP and copeptin levels and APACHE II scores may be used for the determination of AOPP severity and the prediction of AOPP prognosis.