The annual rise in gastrointestinal cancer cases is evident, yet the occurrence of multiple primary malignancies remains comparatively uncommon. In recent years, immunotherapy has swiftly emerged as the leading treatment for several solid tumors, including gastrointestinal cancers. Single treatments might be ineffective, necessitating the need for comprehensive integrative medicine. This study reports a case of multiple cancers, including colorectal and gastric cancers. Diverse systemic treatments, like capecitabine, the combination of capecitabine and paclitaxel liposome, as well as capecitabine with toripalimab, were unsuccessful. Nevertheless, prolonged survival was attained through anti-PD-1 immunotherapy complemented by alternative medicine approaches. The patient has exceeded a 35-month survival post-initial diagnosis and 20-month survival since the subsequent diagnosis, markedly surpassing the prognosis often associated with advanced-stage multiple cancers. In summary, this case underscores the potential effectiveness of a holistic, integrative medical approach in managing advanced multiple malignancies amid drug resistance and disease progression.
Abstract Background: Clinical effectiveness of Azvudine against coronavirus infection and optimal time for initiation of Azvudine treatment to hospitalized COVID-19 patients are not fully understood. Methods: This is a multi-center retrospective cohort study, and five clinical centers of the Chinese People’s Liberation Army General Hospital participated. From omicron pandemics, 6218 hospitalized patients confirmed with COVID-19 from December 10, 2022, to February 20, 2023, were retrieved for this study. After exclusions and propensity score matching , 428 Azvudine recipients and 428 controls were included with a follow-up of 28 days. The primary outcome was all-cause mortality during 28 days of hospitalization, and the secondary outcome was the proportion of patients with clinical improvement up to day 28. Results: The Azvudine group had a lower crude all-cause death rate when compared to the control group (2.82 per 1000 person-days vs. 4.52 per 1000 person-days; HR: 0.63, 95%CI: 0.40-1.00; P =0.038). Notably, the incidence rate of clinical improvement outcome was significantly higher in patients who received Azvudine within 5 days from the onset of symptoms, compared to the control group (Median days: 9 vs. 10; P =0.007). Subgroup analyses showed that chronic lung disease and corticosteroid treatment acted as protective factors (P =0.010; P =0.050). Conclusions: Clinical effectiveness of Azvudine in improving all-cause mortality in COVID-19 patients was seen, and initiation of Azvudine treatment within 5 days of the onset of symptoms was found to be significant. Additionally, the findings revealed the protective effect of Azvudine in COVID-19 patients with chronic lung disease.
Objective To explore an effective treatment of distal tibia fracture.Methods 12 cases of distal tibia fracture receive internal fixation with percutaneous steel plate through microtraumatological techniques.Entocnemial subcutaneous tunnel was built and the supporting steel plate was fixed with screws to achieve indirect reduction.Results The recovery time ranged from 2.6 to 4.8 months,averaging 3.2 months.The follow-up survey lasted 12 to 20 months,averaging 16.3 months.X-ray detections showed that no nonunions of bone fragmentations or loosening were found and the ankle joints concerned recovered satisfactorily.Conclusion Internal fixation of distal tibia fracture with percutaneous supporting steel plate can cause slight trauma,reduce the interference in blood circulation at the fracture sites,promote the healing rate and provide stable fixation of fractured ankle joint.
Our previous study found that deletion of Sorting nexin 10 (SNX10) can protect against colonic inflammation and pathological damage induced by dextran sulfate sodium (DSS). This inspired us that modulation of SNX10 expression in colonic epithelial cells might represent a promising therapeutic strategy for inflammatory bowel disease (IBD).Effective delivery of siRNA/shRNA to silence genes is a highly sought-after means in the treatment of multiple diseases. Here, we encapsulated SNX10-shRNA plasmids (SRP) with polylactide-polyglycolide (PLGA) to make oral nanoparticles (NPs), and then applied them to acute and chronic IBD mice model, respectively. The characteristics of the nanoparticles were assayed and the effects of SRP-NPs on mouse IBD were evaluated.High-efficiency SNX10-shRNA plasmids were successfully constructed and coated with PLGA to obtain nanoparticles, with a particle size of 275.2 ± 11.4mm, uniform PDI distribution, entrapment efficiency of 87.6 ± 2.5%, and drug loading of 13.11 ± 1.38%, displayed dominant efficiency of SNX10 RNA interference in the colon. In both acute and chronic IBD models, SRP-NPs could effectively reduce the loss of mice body weight, relieve the intestinal mucosal damage and inflammatory infiltration, inhibit the expression of inflammatory cytokines IL-1β, IL-23, TNF-α, and down-regulate the expression of toll-like receptors (TLRs) 2 and 4.Oral nanoparticles of SNX10-shRNA plasmid displayed dominant efficiency of SNX10 RNA interference in the colon and ameliorate mouse colitis via TLR signaling pathway. SNX10 is a new target for IBD treatment and nanoparticles of SNX10-shRNA plasmid might be a promising treatment option for IBD.
Coptis chinensis Franch. and Sophora flavescens Ait. is a herbal pair frequently used in treating ulcerative colitis. However, the bio-disposition profile of the major components in the inflamed gut remains unclear, which is essential to understand the pharmacological material basis of this herb pair. Here we established an integral quantitative and chemometric method to deduce the colonic metabolism differences of this herbal pair in normal and colitis mice. With this LC-MS method, a total of 41 components have been found in the Coptis chinensis Franch. and Sophora flavescens Ait. extract, and 28 metabolites were found in the colon after oral administration. Alkaloid and its phase I metabolites were the main components in the colon of normal and colitis mice. The results of principal component analysis at 6 h after oral administration showed significant colonic metabolism differences between normal and colitis mice. Heamap results showed that colitis induced significant changes in the colonic bio-disposition of this herbal pair extract. In particular, in the context of colitis, the phase I metabolism of berberine, coptisine, jatrorrhizine, palmatine,and epiberberine has been inhibited. These results may provide a basis for understanding the pharmacological material basis of Coptis chinensis Franch. and Sophora flavescens Ait. in treating ulcerative colitis.
Abstract In recent years, traditional Chinese medicine (TCM) has made great progress in the prevention and treatment of cancer. It has gradually revealed its characteristics and advantages in clinical practice, including alleviating clinical symptoms, prolonging survival time, decreasing the adverse effects of chemotherapy, and improving living quality. However, clinical TCM treatment of cancer lacks systematic theoretical guidance, because ancient TCM has not formed a recognized theoretical system of cognitive cancer, and there still are different opinions on the pathogenesis of cancer. Due to the complexity of cancer, the essence of cancer pathogenesis has not been described accurately by using common pathogenic factors, such as pathogenic wind, cold, dampness, summer heat, dryness, and fire. Ancient and modern TCM physicians have a similar understanding that the occurrence of cancer is related to toxin. In the 1990s, the thought of cancerous toxin was first proposed by Prof Zhou Zhongying, a TCM master based on more than 60 years of clinical practice, who used “pandemic Qi (Li-Qi) is a specific pathogenic factor of epidemic disease” in Wenyi Lun ( Treatise on Pestilence ) for references. The pathogenesis theory of cancerous toxin was gradually established under the guidance of the thought of cancerous toxin. It holds that the cancerous toxin, a special pathogenic factor of cancer, is the key pathogenesis of the occurrence of malignant tumors. According to the pathogenesis theory of cancerous toxin, the basic pathogenesis of malignant tumors is the accumulation of pathogenic factors and cancerous toxin, and the deficiency of the vital Qi (Zheng-Qi). Therefore, the treatment principle involves eliminating pathogenic factors, resolving cancerous toxin, and supporting the vital Qi. The anticancer detoxification methods and the classification of Chinese medicinal herbs with anticancer detoxification effects were put forward. System theory has much in common with the concepts in the theory system of TCM, such as the universal relation theory, asking for a concrete analysis of concrete conditions, the humanism thought, and so on. This article aims to describe, review, and analyze the pathogenesis theory of cancerous toxin based on system theory for clinical practices.
Sorting nexin 10 (SNX10) has recently been identified as a critical regulator of colorectal carcinogenesis, whose deletion promoted cell proliferation and survival in human CRC cells, and promoted colorectal tumor growth and upregulated amino-acid metabolism in mice. However, what happens when silencing SNX10 in normal human intestinal epithelial cells (IECs) remains unknown, and no drugs targeting SNX10 have been reported. Here, we first investigated the biological function and underlying mechanisms of SNX10 in normal human IECs, and found that α-hederin, a pentacyclic triterpenoid saponin, has a regulatory effect on SNX10 expression.This study aimed to explore the function of SNX10 in IECs to provide a new target for the prevention and treatment of malignant transformation and the intervention mechanism of α-hederin for further development of potential novel agents targeting SNX10.The transfection approach was used to construct SNX10 stable knockdown cells. Cell proliferation was detected by CCK8, clone formation, EdU, flow cytometry, and wound healing assays. Enzyme activity assays for glucose metabolism, qRT-PCR, western blotting, and immunofluorescence staining were performed to investigate the protein expression of signaling pathways.Silencing SNX10 promoted cell proliferation and cycle transition in IECs and increased the activity of key enzymes involved in glucose metabolism. Moreover, DEPDC5 expression was significantly decreased following SNX10 knockdown, followed by activation of the mTORC1 pathway. α-hederin reversed the accelerated cell proliferation, cycle progression, and glucose metabolic activity, as well as the activated mTORC1 pathway caused by SNX10 knockdown, by notably increasing SNX10 expression in a dose-dependent manner.We first reported that knockdown of SNX10 in normal human IECs promoted cell proliferation and activated glucose metabolism by activating the mTORC1 pathway. Meanwhile, we first found that α-hederin down-regulated glucose metabolism activity and slowed cell proliferation by increasing SNX10 expression in IECs.
Colorectal cancer (CRC) remains the third most common tumor worldwide. Ulcerative colitis (UC) could cause chronic inflammation and ulcers in the colon and rectum. UC is a risk factor for a high incidence of CRC, and the incidence of UC-associated CRC (UC-CRC) is still increasing. Chinese medicine prescription, Xian-Lian-Jie-Du decoction (XLJDD), has been proven its efficacy in some UC-CRC patients. However, the mechanism of XLJDD in treating UC-CRC remains unknown. This study aimed to investigate the mechanism of XLJDD in treating UC-CRC.We constructed an AOM/DSS mouse model that could simulate the various stages of UC-CRC in humans. XLJDD and its 5 main components are used to treat the AOM/DSS model, respectively. With the power of high-throughput sequencing technology, we described the mechanism of XLJDD from transcriptomics, proteomics, and single-cell transcriptomics.Our results showed that XLJDD could effectively suppress the occurrence and development of colorectal tumors. Using the weighted correlation network analysis (WGCNA), several mRNA and protein modules that respond to XLJDD have been identified. Moreover, two essential genes, Mfsd2a and Ccdc85c, were caught our attention. They were prognostic markers in CRC patients, and their expression could be significantly modulated by XLJDD, showing their potential as effective targets of XLJDD. In addition, we also discovered that XLJDD could affect the cell composition of the colorectal tumor environment, especially in the infiltration of B cells.We demonstrated that XLJDD could prevent the initiation and development of colorectal tumors by modulating the expression of Mfsd2a and Ccdc85c and reducing the infiltration of B cells in the tumor microenvironment of colorectal tumor.
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