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Through a retrospective analysis of the projects supported by the National Natural Science Foundation of China in the past ten years in the field of Chinese medicine for the treatment of malignant tumors, this article systematically summarized the main research contents and hotspots of Chinese medicine in efficacy enhancement and toxicity reduction. The efficacy enhancement of Chinese medicine mainly included the mitigation of molecule-targeted drug resistance, multidrug resistance, and chemotherapy resistance, synergistic efficacy enhancement, and radiotherapy sensitization. The toxicity reduction is mainly reflected in the alleviation of the side effects of radiotherapy and chemotherapy. In addition, Chinese medicine has advantages in reducing serious adverse reactions of malignant tumors, providing more options for the adjuvant treatment of tumors.
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Disciplinas das Ciências Naturais , Neoplasias , China , Fundações , Humanos , Medicina Tradicional Chinesa , Neoplasias/tratamento farmacológico , Estudos RetrospectivosRESUMO
This study aimed to investigate the clinical predictors, including traditional Chinese medicine tongue characteristics and other clinical parameters for chemotherapy-induced myelosuppression (CIM), and then to develop a clinical prediction model and construct a nomogram. A total of 103 patients with lung cancer were prospectively enrolled in this study. All of them were scheduled to receive first-line chemotherapy regimens. Participants were randomly assigned to either the training group (nâ =â 52) or the test group (nâ =â 51). Tongue characteristics and clinical parameters were collected before the start of chemotherapy, and then the incidence of myelosuppression was assessed after treatment. We used univariate logistic regression analysis to identify the risk predictors for assessing the incidence of CIM. Moreover, we developed a predictive model and a nomogram using multivariate logistic regression analysis. Finally, we evaluated the predictive performance of the model by examining the area under the curve value of the receiver operating characteristic, calibration curve, and decision curve analysis. As a result, a total of 3 independent predictors were found to be associated with the CIM in multivariate regression analysis: the fat tongue (ORâ =â 3.67), Karnofsky performance status score (ORâ =â 0.11), and the number of high-toxic drugs in chemotherapy regimens (ORâ =â 4.78). Then a model was constructed using these 3 predictors and it exhibited a robust predictive performance with an area under the curve of 0.82 and the consistent calibration curves. Besides, the decision curve analysis results suggested that applying this predictive model can result in more net clinical benefit for patients. We established a traditional Chinese medicine prediction model based on the tongue characteristics and clinical parameters, which could serve as a useful tool for assessing the risk of CIM.
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Antineoplásicos , Doenças da Medula Óssea , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Modelos Estatísticos , Prognóstico , LínguaRESUMO
BACKGROUND: Irinotecan is a standard chemotherapeutic agent in small cell lung cancer (SCLC), however, as a common adverse reaction, diarrhea limits the use of irinotecan. Shengjiang Xiexin decoction (SXD) has been used in various gastrointestinal diseases in China two thousand years ago. We designed this clinical trial to supply more evidences on the use of SXD as prophylaxis for irinotecan-induced diarrhea, especially for high-risk population predicted by gene testing of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1). METHODS: In this clinical trial, 120 patients with SCLC were recruited from six hospitals in China. They received two cycles of chemotherapy, meanwhile they were randomized to receive SXD or placebo for 14 days of oral administration in each cycle of chemotherapy. The primary outcome is the incidence of diarrhea. And secondary outcomes include the the degree of diarrhea and neutropenia, the number of chemotherapy cycles with diarrhea, first occurrence time and duration of diarrhea. To evaluate the effect of SXD on the intestine, a rat model with delayed-onset diarrhea induced by irinotecan was established, and the expression of inflammatory factors including IL-1ß, IL-6 and TNF-α, anti-inflammatory factors including IL-10, TGF- ß in jejunal tissue was detected by ELISA. RESULTS: 101 patients (53 in SXD group, 48 in placebo group) completed the trial. The incidence of diarrhea in SXD group and placebo group were 26.42% (14/53) and 52.08% (25/48), respectively (P < 0.05), and the degree of diarrhea also had significant differences (P < 0.05). In UGT1A1 high-risk population, the incidence of diarrhea in two groups were 9.09% and 66.67% (P < 0.05), but there was no significant differences in UGT1A1 low-risk population. The incidence of neutropenia with degree 1-3 between two groups was 20.75% vs 20.83%, 13.21% vs 18.57%, 9.43% vs 20.83% (P < 0.05). No severe adverse events were reported in any group. And animal studies had shown SXD reduced content of IL-1ß, IL-6, TNF-α, increased content of IL-10, TGF-ß in jejunum tissue. CONCLUSIONS: SXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors. Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250 . The preliminary protocol of this clinical study has been published in the journal "Trials" in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).
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BACKGROUND: Alternative splicing (AS) is a molecular event that drives protein diversity through the generation of multiple mRNA isoforms. Growing evidence demonstrates that dysregulation of AS is associated with tumorigenesis. However, an integrated analysis in identifying the AS biomarkers attributed to esophageal carcinoma (ESCA) is largely unexplored. METHODS: AS percent-splice-in (PSI) data were obtained from the TCGA SpliceSeq database. Univariate and multivariate Cox regression analysis was successively performed to identify the overall survival (OS)-associated AS events, followed by the construction of AS predictor through different splicing patterns. Then, a nomogram that combines the final AS predictor and clinicopathological characteristics was established. Finally, a splicing regulatory network was created according to the correlation between the AS events and the splicing factors (SF). RESULTS: We identified a total of 2389 AS events with the potential to be used as prognostic markers that are associated with the OS of ESCA patients. Based on splicing patterns, we then built eight AS predictors that are highly capable in distinguishing high- and low-risk patients, and in predicting ESCA prognosis. Notably, the area under curve (AUC) value for the exon skip (ES) prognostic predictor was shown to reach a score of 0.885, indicating that ES has the highest prediction strength in predicting ESCA prognosis. In addition, a nomogram that comprises the pathological stage and risk group was shown to be highly efficient in predicting the survival possibility of ESCA patients. Lastly, the splicing correlation network analysis revealed the opposite roles of splicing factors (SFs) in ESCA. CONCLUSION: In this study, the AS events may provide reliable biomarkers for the prognosis of ESCA. The splicing correlation networks could provide new insights in the identification of potential regulatory mechanisms during the ESCA development.
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BACKGROUND/AIM: Irritable Bowel Syndrome (IBS) is a common chronic functional bowel disorder and the evidence shows most drug therapies in the treatment of IBS are weak. Recently, some studies showed probiotics may have a positive effect in IBS and they are widely used to improve the symptom of IBS, which indicate probiotics may play an important role in the treatment of IBS. However, the exact effectiveness and safety of probiotics are largely unknown. This systematic review focuses on identifying the efficacy and safety of probiotics in the treatment of IBS. MATERIALS AND METHODS: Data sources were searched up to February 2019. Databases included MEDLINE, CENTRAL, CINAHL, and Embase. Randomized controlled trials (RCTs) comparing probiotics including complex or individual probiotics with placebo or no therapy were screened, extracted, and appraised by two independent reviewers. The data were pooled using a random-effects model. The methodological quality of all RCTs was assessed using the Cochrane risk of bias and Jadad scale. Outcomes included symptom-relevant and patient-relevant characteristics, such as symptom relief, abdominal pain, bloating, flatulence, quality of life, and adverse event. RESULTS: This review includes 28 studies with a total of 3606 participants. Particular combinations of probiotics, or specific species and strains, showed probiotics have beneficial effect on overall IBS symptoms (22 studies, n = 3144, RR of improvement in overall IBS symptoms = 1.5, CI 1.23 to 1.83) or overall IBS symptom and abdominal pain scores (18 studies, n = 2766, SMD = -0.31, CI -0.45 to -0.17). In addition, adverse events were not significantly higher with probiotics (8 studies, n = 923, RR = 1.05; 95% CI 0.85-1.31). However, there was no significant benefit on individual IBS symptom scores and quality of life. CONCLUSION: Current evidence shows particular combinations, species or strains of probiotics are effective for overall IBS symptoms. However, it is hard to derive a definite conclusion due to high heterogeneity and unclear risk of bias of some trials. Large well-designed and rigorous trials are warranted.