Background. Qiweibaizhu decoction (QBD), a classic Chinese herbal formula, has been widely used for treating diarrhea in infants and children with spleen deficiency syndrome for centuries, but its mechanism of action remains unclear. The gut microbiota, short-chain fatty acids (SCFAs), and intestinal mucus are closely associated with diarrhea. Methods. In this study, the composition of the gut microbiota in diarrheal rats was analyzed by 16S rDNA amplicon sequencing. The concentrations of colon SCFAs were determined using gas chromatography-mass spectrometry (GC-MS). The expression of mucin 2 (MUC2) in the colon was detected by immunofluorescence. Results. Diarrhea significantly changed the diversity and structure of the gut microbiota and disrupted the mucus barrier in juvenile rats. QBD did not significantly change the diversity and structure of the intestinal flora, but it enhanced the increasing tendencies of Verrucomicrobia and Akkermansia and decreased the abundance of Turicibacter ( P = 0.037 ) and Flavonifractor ( P = 0.043 ). QBD tends to repair the mucus layer and promote MUC2 expression in juvenile rats with diarrhea. Moreover, S. boulardii significantly increased the abundance of Parasutterella ( P = 0.043 ). In addition, QBD treatment tends to increase the propionic acid concentration during diarrhea, but its levels of acetic acid, propionic acid, butyric acid, and total SCFAs were lower than those in the S. boulardii group. Conclusion. S. boulardii significantly increased the abundance of Parasutterella, leading to increased production of acetic acid, propionic acid, and butyric acid, consequently leading to alleviation of diarrhea. In comparison, QBD affected diarrhea via regulation of the intestinal flora, especially by increasing the abundance of Verrucomicrobia and Akkermansia, resulting in mucus barrier repair, protection of the intestines, and treatment of diarrhea.
The standard third-line treatment of metastatic colorectal cancer (mCRC) includes the small-molecule anti-vascular drugs (Regofenib and Fruquintinib) and the chemotherapy drug trifluridine and tipiracil hydrochloride (TAS-102). There is no standard treatment for mCRC if the third-line treatment failed. Therefore, it is a pressing need to develop new therapeutic approaches to improve the survival of patients who developed drug resistance to the third-line treatment. In this study, we report a case of mCRC with RAS/BRAF wild-type, who was successfully treated using cetuximab in combination with fruquintinib after resistance to chemotherapy, bevacizumab, cetuximab and regorafenib. This patient responded to this combination regimen. Then, we discuss the mechanisms of action of this combination. Furthermore, we introduce the clinical trials on the combination regimens of anti-EGFR with anti-vascular monoclonal antibodies. Finally, we discuss the clinical explorations of using combination of anti-EGFR with small-molecule anti-VEGF drugs and their potential benefits. The clinical effects of small-molecule anti-vascular drugs in combination with anti-EGFR in the treatment of CRC warrant further explored.
Objective: The objective of our current research is to compare the different psychological interventions and distinguish the most effective way to treat psychological crisis according to different clinical manifestations in people affected by coronavirus disease 2019 (COVID-19). No previous systematic review has provided a comprehensive overview by performing a Bayesian network meta-analysis of this current topic.Method: A systematic review and a Bayesian network meta-analysis were conducted on randomized controlled trials (RCTs), non-RCTs, case–control studies, self-controlled case series (SCCS), cohort studies, and cross-sectional studies of all the available interventions for psychological crisis in people affected by COVID-19. We searched the electronic databases EMBASE, PubMed, Web of Science, PsycINFO, and Cochrane Library, as well as the Chinese databases such as Sinomed, Chinese Biomedicine Literature (CBM), Chinese Scientific Journal Database (VIP), WanFang Database, and China National Knowledge Infrastructure (CNKI), from 2019 to April 30, 2020. The main outcomes were self-rating anxiety scale (SAS), self-rating depression scale (SDS), patient health questionnaire (PHQ-9), and symptom checklist (SCL-90). The study is registered with Inplasy, number 202050076.Result: Sixteen self-controlled case series (SCCS) comprising 1,147 participants compared five different psychological interventions with four different measurement scales were included in this study. For effectiveness, all the psychological therapies were significantly more effective than before intervention. Our results showed that supportive therapy (ST), which is adjusted to the COVID-19-related mental crisis, is the best treatment compared with behavioral therapy (BT), nursing-based psychological therapy (NBPT), traditional Chinese medicine therapy (TCMT), and COVID-19-related standard training (CRST) at reducing the anxiety-related symptoms assessed by SAS. When measured by SDS, BT was better than ST and NBPT treatment for reducing the depression symptoms. And ST was better than BT and ST+BT as assessed by PHQ-9. In the end, the last network meta-analysis indicated that NBPT was more effective than ST by the measurement of SCL-90.Conclusion: Our research suggested the potential effectiveness of psychological interventions for decreasing psychological crisis in people affected by COVID-19 and try to introduce the best effective treatment options for clinical practice according to the clinical manifestations of psychological problems, but further confirmation from high-quality RCTs is needed.
Background: Diarrheal disease currently claims the lives of approximately 500,000 children each year. Rotaviruses are the pathogens primarily responsible for more severe cases and more than one-third of diarrhea-associated deaths in children under 5 years old globally. At present, commonly used drug therapies for rotavirus diarrhea in Western medicine, such as oral rehydration salts, montmorillonite, probiotics, and nitazoxanide, often cannot achieve satisfactory curative effects. Moreover, infants’ and children's compliance with drugs and injections is often lower than their compliance with acupoint application therapy. A large number of studies have shown that acupoint application can increase the clinical cure rate and shorten the duration of diarrhea. However, there is a lack of systematic reviews on the safety and efficacy of acupoint application in the treatment of rotavirus diarrhea. Therefore, we will conduct a study to evaluate the safety and efficacy of acupoint application for rotavirus diarrhea in infants and children. Methods: We will search the relevant medical literature using PubMed, EMBASE, Web of Science, Cochrane CENTRAL, China National Knowledge Infrastructure, the Wanfang Database, the Chinese Biomedical Literature Database, and the Chinese Scientific Journal Database from inception to August 2020. Both MeSH and free text terms will be utilized to obtain the maximum numbers of papers. No language restrictions will be applied, and the publication type will be limited to randomized controlled trials. Two teams will independently review and assess the studies for inclusion in the review. RevMan V 5.0 software will be applied for data extraction. The methodological quality of the included studies will be evaluated according to the Cochrane Handbook. Results: The results of this study will be published in a peer-reviewed journal. Conclusion: The conclusion of this systematic review will provide evidence regarding whether acupoint application is an effective intervention for infants and children with rotavirus diarrhea. INPLASY registration number: INPLASY202070123.
cohort, separately. TMB was defined as the number of somatic nonsynonymous somatic mutations per megabase in the coding region of WES. The tumor-related immune cells infiltration level difference between mutant and wildtype tumors were inferred using TIMER 2.0 (Wilcoxon test). The association between MUC16 mutation states and the efficacy of ICIs was performed in melanoma patients from Miao2018 pan-cancer ICIs treatment cohort.Results: In total, the alteration frequency of MUC16 gene in COAD was 28% (148/526) in TCGA cohort and 27% (18/66) in Chinese cohort. In TCGA cohort, the expression of MUC16 of COAD tumor tissues was significantly higher than adjacent normal tissues (p<0.001). The level of infiltration of CD8+ T cell, B cell, T cell regulatory (Tregs) and NK cell were all significantly increased in mutated tumors compared with wild-type tumors (p < 0.05). The mutant tumors with significantly higher inferred M1 macrophages than wildtype (p¼0.0014), but not in M2 macrophages. In Chinese cohort, the TMB level was higher in mutant group compared to wild-type group (median TMB, mut vs wt ¼ 18.26 vs 2.72 Mut/Mb, p < 0.0001). The percentage of microsatellite instability-high (MSI-H) in MUC16 mutant tumors was 50.00%, while 8.33% in wildtype tumors (Fisher's exact test, p ¼ 0.0005). The overall survival (OS) of MUC16 mutation group (n¼43) were significantly longer than wild-type group (n¼108) (median OS, mutation vs wild-type ¼ 20.33 vs 9.77 months; HR 0.59[95% CI 0.37-0.92]; p ¼ 0.019). Conclusions:The MUC16 mutation COAD tumors had highly TMB levels and infiltrating lymphocytes, which may serve as a potential biomarker to guide ICB therapy in COAD.
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