[Banxia Xiexin Decoction inhibiting colitis-associated colorectal cancer infected with Fusobacterium nucleatum by regulating Wnt/ß-catenin pathway].

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.

[Tongxie Yaofang regulates tumor-associated macrophage polarization in colorectal cancer under chronic stress].

This study aims to investigate the intervention effect and mechanism of Tongxie Yaofang in regulating tumor-associated macrophage polarization on colorectal cancer under chronic stress. BALB/C mice were randomized into blank, control, model, mifepristone, and low-, medium-, and high-dose Tongxie Yaofang groups. The other groups except the blank and model groups were subjected to chronic restraint stress and subcutaneous implantation of colon cancer cells for the modeling of colon cancer under stress. Du-ring this period, the body mass and tumor size of each group of mice were recorded. The degree of depression in mice was assessed by behavioral changes. Enzyme-linked immunosorbent assay was employed to determine the levels of cortisol(CORT), 5-hydroxytryptamine(5-HT), norepinephrine(NE), M1-associated inflammatory cytokines [interleukin(IL)-1ß, IL-12, and tumor necrosis factor(TNF)-α], and M2-associated inflammatory cytokines(IL-4 and IL-10) in the serum. The tumor growth of mice in each group was regularly monitored by in vivo imaging. The histopathological changes of tumors in each group of mice were observed by hematoxylin-eosin staining. The proportions of CD86 and CD206 in the tumor tissue were detected by flow cytometry and immunofluorescence staining. Western blot was employed to determine the protein levels of Janus kinase(JAK)1, JAK2, JAK3, signal transducer and activator of transcription(STAT)3, and STAT6 in the tumor tissue. The results showed that chronic stress increased the immobility time of mice, elevated the serum levels of CORT, IL-4, and IL-10, lowered the levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and promoted the growth of subcutaneous tumors. The tumor cells in the tumor tissue grew actively, with obvious atypia and up-regulated protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and down-regulated protein level of CD86. The treatment with Tongxie Yaofang shortened the immobility time of mice, lowered the serum levels of CORT, IL-4, and IL-10, elevated the serum levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and inhibited the growth of subcutaneous tumors in mice. Moreover, the treatment caused different degrees of necrosis in the tumor tissues, down-regulated the protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and up-regulated the protein level of CD86. In summary, Tongxie Yaofang can promote the transformation of M2 macrophages to M1 macrophages and change the tumor microenvironment under chronic stress to inhibit the development of colorectal cancer, which may be related to the JAK/STAT signaling pathway.

[Decursin affects proliferation, apoptosis, and migration of colorectal cancer cells through PI3K/Akt signaling pathway].

We investigated the effects of decursin on the proliferation, apoptosis, and migration of colorectal cancer HT29 and HCT116 cells through the phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway. Decursin(10, 30, 60, and 90 µmol·L~(-1)) was used to treat HT29 and HCT116 cells. The survival, colony formation ability, proliferation, apoptosis, wound hea-ling area, and migration of the HT29 and HCT116 cells exposed to decursin were examined by cell counting kit-8(CCK8), cloning formation experiments, Ki67 immunofluorescence staining, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blot was employed to determine the expression levels of epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2-associated X protein(Bax), tumor suppressor protein p53, PI3K, and Akt. Compared with the control group, decursin significantly inhibited the proliferation and colony number and promoted the apoptosis of HT29 and HCT116 cells, and it significantly down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. Decursin inhibited the wound healing and migration of the cells, significantly down-regulated the expression of N-cadherin and vimentin, and up-regulated the expression of E-cadherin. In addition, it significantly down-regulated the expression of PI3K and Akt and up-regulated that of p53. In summary, decursin may regulate epithelial-mesenchymal transition(EMT) via the PI3K/Akt signaling pathway, thereby affecting the proliferation, apoptosis, and migration of colorectal cancer cells.

Evaluation of circulating small extracellular vesicle-derived miRNAs as diagnostic biomarkers for differentiating between different pathological types of early lung cancer.

Lung cancer is the leading cause of cancer-related death worldwide. MicroRNAs (miRNAs) in circulating small extracellular vesicles (sEVs) have been suggested to be potential biomarkers for cancer diagnosis. The present study was designed to explore whether plasma-derived sEV miRNAs could be utilized as diagnostic biomarkers for differentiating between early-stage small cell lung cancer (SCLC) and early-stage non-small cell lung cancer (NSCLC). We compared the miRNA profiles of plasma-derived sEVs from healthy individuals, patients with early-stage SCLC and patients with early-stage NSCLC. Next-generation sequencing was used to screen for differentially expressed miRNAs (DEMs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the potential functions of these DEMs. Weighted gene coexpression network analysis (WGCNA) was used to identify the different pathology-related miRNA modules. We found that 22 DEMs were significantly different among healthy individuals, patients with early-stage SCLC, and patients with early-stage NSCLC. We selected six representative DEMs for validation by qRT‒PCR, which confirmed that miRNA-483-3p derived from plasma sEVs could be used as a potential biomarker for the diagnosis of early-stage SCLC, miRNA-152-3p and miRNA-1277-5p could be used for the diagnosis of early-stage NSCLC respectively.

Gabapentin has Longer-Term Efficacy for the Treatment of Chronic Pelvic Pain in Women: A Systematic Review and Pilot Meta-analysis.

INTRODUCTION: Gabapentin has potential analgesic benefits in patients with neuropathic pain, such as post-herpetic neuralgia and diabetic peripheral neuropathy neuropathic pain. However, its efficacy in women with chronic pelvic pain (CPP) remains contradictory. In the present study, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to ascertain the efficacy of this treatment. METHODS: We systematically reviewed RCTs published in PubMed, Embase, the Cochrane Library, Web of Science, and Google Scholar databases, up to July 2021. These articles compared gabapentin with placebo or any other active treatment for CPP in women, with 'the change in pain scores from the baseline during the first 3 and 6 months of treatment' taken as the primary outcome. We considered reductions equivalent to 1.0 cm for primary outcomes to be clinically important. RESULTS: Four studies, comprising 469 participants, were included in our meta-analysis. Results revealed that the gabapentin group had significantly higher change in pain intensity scores from baseline to 3 months [weighted mean difference (WMD) - 0.61 cm; 95% confidence interval (CI) - 0.97 to - 0.25; I2 = 0%; p = 0.0009] and 6 months (WMD - 1.38 cm; 95% CI - 1.89 to - 0.88; I2 = 0%; p < 0.00001), relative to the control group. The difference of 6-month pooled result was more clinically important. Results from analysis of secondary outcomes showed that gabapentin had no beneficial efficacy during the first 3 months of treatment. Although gabapentin treatment was associated with a higher risk of dizziness and somnolence, no statistically significant differences were observed with regards to the total incidence of adverse events. CONCLUSIONS: Overall, gabapentin could be a potential treatment option for CPP in women. However, as a pilot study, further studies are needed to explore the longer-term benefits and definite safety of this therapy in the future. REGISTRATION NUMBER: PROSPERO registration number CRD42021249421.

The Analgesic Benefits of Ketorolac to Local Anesthetic Wound Infiltration Is Statistically Significant But Clinically Unimportant: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Even though ketorolac-infiltration is said to provide superior postoperative analgesic benefits in different surgical procedures, its safety and efficacy remain to be validated because of the lack of high-quality evidence. We aimed to summarize the efficacy and safety of ketorolac-infiltration based on published randomized-controlled trials (RCTs). Approach: This work followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, assessing the methodological quality of systematic reviews and the Cochrane Collaboration recommendations. We searched for RCTs evaluating the efficacy of ketorolac-infiltration in adults in the PubMed, Web of Science, Embase, Cochrane Library, Chinese databases, and Google Scholar. The two co-primary outcomes of this meta-analysis were rescue analgesic consumption in the 24-h postoperative period and rest pain scores. Results: Twelve trials (761 patients) were analyzed. Ketorolac-infiltration provided a clinically unimportant benefit in morphine consumption (mean difference, -2.81 mg; 95% confidence interval [CI], -5.11 to -0.50; p = 0.02; moderate-quality evidence). Low-to-moderate quality evidence supported a brief (2-6 h), clinically subtle, but statistically consistent effect of surgical site ketorolac-infiltration in reducing wound pain at rest. High-quality evidence supported shorter hospital stays for surgical patients receiving local ketorolac-infiltration when compared to controls (mean difference, -0.12 days; 95% CI, -0.17 to -0.08; p < 0.00001). Further, ketorolac-infiltration does not improve any opioid-related side effects. Innovation: Ketorolac-infiltration provides statistically significant but clinically unimportant benefits for improving postoperative wound pain. Conclusion: Overall, despite the fact that current moderate-to-high quality of evidence does not support routine using of ketorolac as an adjuvant to local anesthetic for wound infiltration, these findings underscore the importance of optimizing agents and sustained delivery parameters in postoperative local anesthetic practice. Clinical Trials.gov ID: CRD42021229095.

[Localization of the bronchial air leakage in pneumothorax by injection of human albumin foam].

OBJECTIVE: To evaluate the efficacy and safety of a new method to determine the bronchus for air leakage in pneumothorax by injection of human albumin foam. METHODS: In 29 cases with pneumothorax, the bronchus responsible for air leakage was localized by injecting foam of human albumin into target bronchus under direct view of bronchoscopy. RESULTS: The bronchus for air leakage was successfully localized in all the 29 cases of pneumothorax. The average time for locating (from injection of the foam to the localization of the bronchus) was (4.0 ± 1.2) min, and the average amount of 20% human albumin used was (8.0 ± 2.6) ml for each patient. The air leakage was treated accordingly, and occlusion by fibrin glue was successfully carried out in 21 cases and by OB glue in 8 cases. Severe cough was noted in 6, fever in 4, thoracic bleeding in 4 cases, and chest pain in 1 case. CONCLUSION: Injection of human albumin foam into target bronchus under bronchoscopy was a simple, safe and effective method for the localization of the bronchus for air leakage in pneumothorax.

[Evaluation of direct digital radiography image quality in dentistry].

PURPOSE: To evaluate the quality of direct digital radiograph according to its application in dentistry. METHODS: 1195 patients with dental caries, periodontal diseases, periapical diseases, trauma of teeth or hypodontia were tested with Trophy elitys Radio Visio Graphy(RVG) and the quality of the tests was evaluated at four levels. RESULTS: It was convenient to operate RVG and easy to save the images, which reduced the amount of X-rays. 1587 pictures were taken, among which 92.3% was at level I, 6.3% was at level II,1.14% was at level III and level IV. CONCLUSIONS: The quality of the images at different positions is good, which can meet the requirement for clinical diagnosis. However, the radiography receptor should be improved for better images.