Fu-Zheng-Tong-Luo formula promotes autophagy and alleviates idiopathic pulmonary fibrosis by controlling the Janus kinase 2/signal transducer and activator of transcription 3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fu-Zheng-Tong-Luo (FZTL) formula is a Chinese herbal prescription which is used to treat idiopathic pulmonary fibrosis (IPF). We previously reported that the FZTL formula could improve IPF injury in rats; however, the mechanism remains unelucidated. AIM OF THE STUDY: To elucidate the effects and mechanisms of the FZTL formula on IPF. MATERIALS AND METHODS: The bleomycin-induced pulmonary fibrosis rat model and transforming growth factor-ß-induced lung fibroblast model were used. Histological changes and fibrosis formation were detected in the rat model after treatment with the FZTL formula. Furthermore, the effects of the FZTL formula on autophagy and lung fibroblast activation were determined. Moreover, the mechanism of FZTL was explored using transcriptomics analysis. RESULTS: We observed that FZTL alleviated IPF injury in rats and inhibited inflammatory responses and fibrosis formation in rats. Moreover, it promoted autophagy and inhibited lung fibroblast activation in vitro. Transcriptomics analysis revealed that FZTL regulates the Janus kinase 2 (JAK)/signal transducer and activator of the transcription 3 (STAT) signaling pathway. The JAK2/STAT3 signaling activator interleukin 6 inhibited the anti-fibroblast activation effect of the FZTL formula. Combined treatment with the JAK2 inhibitor (AZD1480) and autophagy inhibitor (3-methyladenine) did not enhance the antifibrotic effect of FZTL. CONCLUSIONS: The FZTL formula can inhibit IPF injury and lung fibroblast activation. Its effects are mediated via the JAK2/STAT3 signaling pathway. The FZTL formula may be a potential complementary therapy for pulmonary fibrosis.

Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19: A retrospective cohort study.

OBJECTIVE: Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19. METHODS: A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored. RESULTS: COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3+ T cells increased in the treatment group compared to the control group ([317.09 ± 274.39] vs. [175.02 ± 239.95] counts/µL, P = 0.030). No statistically significant differences were detected in the median improvement in levels of CD4+ T cells (173 vs. 107 counts/µL, P = 0.208) and CD45+ T cells (366 vs. 141 counts/µL, P = 0.117) between the treatment and control groups. CONCLUSION: Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3+ T cells.

Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study.

OBJECTIVE: To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action. METHODS: A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups. RESULTS: The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044). CONCLUSION: In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.

Prediction of Poor Prognosis of HCC by Early Warning Model for Co-Expression of miRNA and mRNA Based on Bioinformatics Analysis.

OBJECTIVE: Hepatocellular Carcinoma (HCC) has the highest mortality rate worldwide with the intractability of its extremely complicated pathogenesis and unclear mechanism. The limited survival highlights the need for the further detection of prognosis for HCC. MicroRNAs (miRNAs) and messenger RNAs (mRNAs) have been identified as regulatory factors and target genes in human cancers, while some studies also found post-transcriptional modification plays a crucial role in the occurrence and development of HCC. The present study aimed to elucidate the prognostic significance of miRNA and mRNA models in HCC. METHODS: Data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases. The miRNA and mRNA expressions were tested by the Wilcoxon and used funrich software to predict mRNA that might be related to miRNA. Then we determined the intersection with overlapped mRNA and miRNA Venn diagram, and screened out hub gene by using Degree algorithm in Cytoscape software. The COX models, with TCGA data as the training set and ICGC data as the test set, were constructed. All patients were divided into high-risk and low-risk groups. Data on overall survival of different groups were collected and analyzed by Kaplan-Meier method, and independent risk factors affecting prognosis were assessed by Cox analysis. RESULTS: The miRNA and mRNA polygenic risk model showed a good true positive rate. Kaplan-Meier curve and Cox analysis suggested that the high-risk group was associated with poor prognosis, and the risk score could be used as an independent risk factor for HCC. CONCLUSION: Tumor risk models constructed in this study could effectively predict the prognosis of patients, which is expected to provide a reference for the prognostic stratification and treatment strategy development of HCC.

Neurotensin promotes cholangiocarcinoma metastasis via the EGFR/AKT pathway.

Cholangiocarcinoma (CCA) is a fatal disease with increasing morbidity and poor prognosis due to poor response to conventional chemotherapy or radiotherapy. Neurotensin (NTS) has long been recognized as an important factor in the central nervous system and as an endocrine agent in the peripheral circulation via NTS receptor (NTSR) mediated actions. In recent years, NTS has been implicated in the carcinogenesis of numerous cancers; however, its role in cholangiocarcinoma remains obscure. Here, we observed the expression of NTS in cholangiocarcinoma vs. non-cancerous tissues and found that up-regulation of NTS facilitated cholangiocarcinoma cell metastasis and down-regulation of NTS inhibited their migration ability. Mechanistically, NTS drove cholangiocarcinoma cell metastasis via the EGFR/AKT pathway. Both the PI3-K inhibitor LY294002 or EGFR inhibitor Erlotinib stopped the discrepant metastatic capacity between NTS-depleted cholangiocarcinoma cells and control cells, further confirming that EGFR/AKT was required in NTS-promoted cholangiocarcinoma cell metastasis. More importantly, overexpression of NTS predicted poor prognosis of CCA patients. In summary, NTS could promote cholangiocarcinoma cells metastasis by amplifying EGFR/AKT signaling and may therefore be useful to predict patient prognosis.

Glasgow Prognostic Score predicts prognosis of intrahepatic cholangiocarcinoma.

High Glasgow Prognostic Score (GPS) has been associated with poor prognosis in patients with lung, ovarian, colorectal and renal cancer, as well as hepatocellular carcinoma. The aim of this study was to investigate the prognostic value of GPS in patients with intrahepatic cholangiocarcinoma (ICC) undergoing partial hepatectomy. A total of 72 patients with pathologically confirmed ICC were classified according to their GPS scores assigned based on the preoperative levels of C-reactive protein (CRP) and albumin. Their clinicopathological data were retrospectively assessed using univariate and multivariate analysis to determine their association with overall survival and recurrence. High GPS scores in ICC patients were associated with preoperative levels of CRP (P<0.001) and albumin (P<0.001), frequency of ascites accumulation (P=0.035), lymph node metastasis (P=0.002) and tumour size (P=0.005). On univariate analysis, preoperative levels of CRP (P<0.001), albumin (P=0.016) and carbohydrate antigen 19-9 (P=0.038), hepatitis B virus (HBV) positivity (P=0.009), occurrence of lymph node metastasis (P=0.001), Child-Pugh class B (P=0.013) and high tumour-node-metastasis (TNM) stage (P=0.002) were found to be associated with the 1- and 3-year overall survival. Multivariate analysis suggested that GPS score (HR=2.037, 95% CI: 1.092-3.799, P=0.025), TNM classification (HR=2.000, 95% CI: 1.188-3.367, P=0.009) and HBV positivity (HR=0.559 95% CI: 0.328-0.953, P=0.032) were independently associated with patient survival. High GPS scores also predicted ICC recurrence. In conclusion, our results demonstrated that GPS may serve as an independent marker of prognosis in patients with ICC following partial hepatectomy.

A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer.

BACKGROUND: People's Republic of China is one of the countries with the highest incidence of gastric cancer, accounting for 45% of all new gastric cancer cases in the world. Therefore, strong prognostic markers are critical for the diagnosis and survival of Chinese patients suffering from gastric cancer. Recent studies have begun to unravel the mechanisms linking the host inflammatory response to tumor growth, invasion and metastasis in gastric cancers. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have prognostic value in many types of malignant solid tumors. OBJECTIVE: To compare the prognostic value of inflammation-based prognostic scores and tumor node metastasis (TNM) stage in patients undergoing gastric cancer resection. METHODS: The inflammation-based prognostic scores were calculated for 207 patients with gastric cancer who underwent surgery. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic nutritional index (PNI), and prognostic index (PI) were analyzed. Linear trend chi-square test, likelihood ratio chi-square test, and receiver operating characteristic were performed to compare the prognostic value of the selected scores and TNM stage. RESULTS: In univariate analysis, preoperative serum C-reactive protein (P<0.001), serum albumin (P<0.001), GPS (P<0.001), PLR (P=0.002), NLR (P<0.001), PI (P<0.001), PNI (P<0.001), and TNM stage (P<0.001) were significantly associated with both overall survival and disease-free survival of patients with gastric cancer. In multivariate analysis, GPS (P=0.024), NLR (P=0.012), PI (P=0.001), TNM stage (P<0.001), and degree of differentiation (P=0.002) were independent predictors of gastric cancer survival. GPS and TNM stage had a comparable prognostic value and higher linear trend chi-square value, likelihood ratio chi-square value, and larger area under the receiver operating characteristic curve as compared to other inflammation-based prognostic scores. CONCLUSION: The present study indicates that preoperative GPS and TNM stage are robust predictors of gastric cancer survival as compared to NLR, PLR, PI, and PNI in patients undergoing tumor resection.

The Glasgow Prognostic Score is an independent prognostic predictor of hepatocellular carcinoma following radical resection.

BACKGROUND: Some prognostic evaluation systems were developed to postoperatively predict the outcome of hepatocellular carcinoma (HCC) patients, mainly based on the cancer itself and the underlying liver diseases. However, none of these prognostic evaluation systems have so far been universally accepted. A simple and feasible scoring system is still lacking for the prediction of prognosis of HCC patients following resection. We aimed to uncover the correlation between the preoperative Glasgow Prognostic Score (GPS) and the clinical outcome of HCC patients after radical resection. METHODS: The patients were separated into 3 subgroups on the basis of their GPSs. The prognostic significance of the GPS in the patient cohort was evaluated by survival analysis. RESULTS: On univariate analysis, the levels of C-reactive protein and albumin, the Child-Pugh class, vascular invasion, tumor number, tumor size, the tumor/node/metastasis (TNM) stage, and the GPS were associated with overall survival and time to recurrence of HCC patients after radical resection. On multivariate analysis, the tumor size, albumin level, and GPS were independently associated with the outcome of HCC postoperatively. CONCLUSION: The GPS is an independent biomarker for prognostic prediction of HCC following radical resection.