Diagnostic performance of volatile organic compounds analysis and electronic noses for detecting colorectal cancer: a systematic review and meta-analysis.

Introduction: The detection of Volatile Organic Compounds (VOCs) could provide a potential diagnostic modality for the early detection and surveillance of colorectal cancers. However, the overall diagnostic accuracy of the proposed tests remains uncertain. Objective: This systematic review is to ascertain the diagnostic accuracy of using VOC analysis techniques and electronic noses (e-noses) as noninvasive diagnostic methods for colorectal cancer within the realm of clinical practice. Methods: A systematic search was undertaken on PubMed, EMBASE, Web of Science, and the Cochrane Library to scrutinize pertinent studies published from their inception to September 1, 2023. Only studies conducted on human subjects were included. Meta-analysis was performed using a bivariate model to obtain summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was deployed for quality assessment. The protocol for this systematic review was registered in PROSPERO, and PRISMA guidelines were used for the identification, screening, eligibility, and selection process. Results: This review encompassed 32 studies, 22 studies for VOC analysis and 9 studies for e-nose, one for both, with a total of 4688 subjects in the analysis. The pooled sensitivity and specificity of VOC analysis for CRC detection were 0.88 (95% CI, 0.83-0.92) and 0.85 (95% CI, 0.78-0.90), respectively. In the case of e-nose, the pooled sensitivity was 0.87 (95% CI, 0.83-0.90), and the pooled specificity was 0.78 (95% CI, 0.62-0.88). The area under the receiver operating characteristic analysis (ROC) curve for VOC analysis and e-noses were 0.93 (95% CI, 0.90-0.95) and 0.90 (95% CI, 0.87-0.92), respectively. Conclusion: The outcomes of this review substantiate the commendable accuracy of VOC analysis and e-nose technology in detecting CRC. VOC analysis has a higher specificity than e-nose for the diagnosis of CRC and a sensitivity comparable to that of e-nose. However, numerous limitations, including a modest sample size, absence of standardized collection methods, lack of external validation, and a notable risk of bias, were identified. Consequently, there exists an imperative need for expansive, multi-center clinical studies to elucidate the applicability and reproducibility of VOC analysis or e-nose in the noninvasive diagnosis of colorectal cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023398465.

[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.

Progressive coronal caudal curve after corrective osteotomies for congenital cervicothoracic scoliosis: incidence and predictors.

OBJECTIVE: Postoperative progressive coronal caudal curve (PCC) was characterized by a postoperative de novo caudal S-curve ≥ 20° following congenital cervicothoracic scoliosis (CTS) corrective osteotomies, and at least 20° greater than the preoperative measurement, while the incidence was uncertain and the pathogenesis was equivocal. The objective of this study was to investigate the morbidity and potential factors contributing to PCC following CTS surgery. METHODS: This study reviewed 72 CTS patients between 2005 and 2021. Patients were categorized into two groups according to the absence or presence of PCC at last follow-up, namely the nonprogressive curve group (NPC-group) and the progressive curve group (PC-group). Demographics, radiographic data and the Scoliosis Research Society-22 (SRS-22) questionnaire results were reviewed. Multivariate linear regression analyses were utilized to determine possible predictors for PCC. RESULTS: PCC was observed in 11 (15%) of the total 72 patients. Compared with the NPC-group, the PC-group exhibited greater postoperative residual local curve (24.0 ± 9.7° vs. 9.1 ± 4.4°, P < 0.001), upper instrumented vertebra (UIV) tilt (16.9 ± 7.4° vs. 6.2 ± 3.7°, P < 0.001), T1 tilt (14.3 ± 9.4° vs. 6.6 ± 3.9°, P = 0.022) and neck tilt (10.1 ± 6.7° vs. 3.7 ± 2.5, P = 0.009). The multivariable linear regression demonstrated that the larger postoperative UIV tilt, residual local curve and neck tilt were associated with PCC. In addition, patients with PCC showed lower SRS-22 scores in terms of pain, mental health, self-image and satisfaction (P < 0.05). CONCLUSIONS: The morbidity of PCC was 15% in CTS patients who underwent corrective osteotomies. Greater residual local curve, postoperative UIV tilt and neck tilt were identified as predictors for PCC.

A comprehensive review of phytochemicals targeting macrophages for the regulation of colorectal cancer progression.

BACKGROUND: Phytochemicals are natural compounds derived from plants, and are now at the forefront of anti-cancer research. Macrophage immunotherapy plays a crucial role in the treatment of colorectal cancer (CRC). In the context of colorectal cancer, which remains highly prevalent and difficult to treat, it is of research value to explore the potential mechanisms and efficacy of phytochemicals targeting macrophages for CRC treatment. PURPOSE: The aim of this study was to gain insight into the role of phytochemical-macrophage interactions in regulating CRC and to provide a theoretical basis for the development of new therapeutic strategies in the future. STUDY DESIGN: This review discusses the potential immune mechanisms of phytochemicals for the treatment of CRC by summarizing research of phytochemicals targeting macrophages. METHODS: We reviewed the PubMed, EMBASE, Web of Science and CNKI databases from their initial establishment to July 2023 to classify and summaries phytochemicals according to their mechanism of action in targeting macrophages. RESULTS: The results of the literature review suggest that phytochemicals interfere with CRC development by affecting macrophages through four main mechanisms. Firstly, they modulate the production of cytotoxic substances, such as NO and ROS, by macrophages to exert anticancer effects. Secondly, phytochemicals polarize macrophages towards the M1 phenotype, inhibit M2 polarisation and enhance the anti-tumour immune responses. Thirdly, they enhance the secretion of macrophage-derived cytokines and alter the tumour microenvironment, thereby inhibiting tumor growth. Finally, they activate the immune response by targeting macrophages, triggering the recruitment of other immune cells, thereby enhancing the immune killing effect and exerting anti-tumor effects. These findings highlight phytochemicals as potential therapeutic strategies to intervene in colorectal cancer development by modulating macrophage activity, providing a strong theoretical basis for future clinical applications. CONCLUSION: Phytochemicals exhibit potential anti-tumour effects by modulating macrophage activity and intervening in the colorectal cancer microenvironment by multiple mechanisms.

Banxia Xiexin Decoction delays colitis-to-cancer transition by inhibiting E-cadherin/ß-catenin pathway via Fusobacterium nucleatum FadA.

ETHNOPHARMACOLOGICAL RELEVANCE: Colitis is an important risk factor for the occurrence of colorectal cancer (CRC), and the colonization of Fusobacterium nucleatum (Fn) in the intestines accelerates this transformation process. Banxia Xiexin Decoction (BXD), originating from Shanghanlun, is a classic prescription for treating gastrointestinal diseases. Current researches indicate that BXD can effectively delay the colitis-to-cancer transition, but it is still unclear whether it can inhibit Fn colonization to achieve this delaying effect. AIM OF STUDY: This study explored the effect and mechanism of BXD in inhibiting Fn intestinal colonization to delay colitis-to-cancer transition. MATERIALS AND METHODS: We constructed a mouse model of colitis-to-cancer transition by regularly gavaging Fn combined with azoxymethane (AOM)/dextran sodium sulfate (DSS), and administered BXD by gavage. We monitored the body weight of mice, measured the length and weight of their colons, and calculated the disease activity index (DAI) score. The growth status of colon tumors was observed by hematoxylin and eosin (H&E) staining, and the changes in gut microbiota in each group of mice were detected by 16S rDNA analysis. Immunohistochemistry was used to detect the expression of E-cadherin and ß-catenin in colon tissues, and immunofluorescence was used to observe the infiltration of M2 macrophages in colon tissues. In cell experiments, we established a co-culture model of Fn and colon cancer cells and intervened with BXD-containing serum. Malignant behaviors such as cell proliferation, invasion, and migration were detected, as well as changes in their cell cycle. We examined the protein levels of E-cadherin, ß-catenin, Axin2, and Cyclin D1 in each group were detected by Western blot. We used US1 strain (fadA-) as a control and observed the effects of BXD-containing serum on Fn attachment and invasion of colon cancer cells through attachment and invasion experiments. RESULTS: BXD can inhibit the colitis-to-cancer transition in mice infected with Fn, reduce crypt structure damage, improve gut microbiota dysbiosis, upregulate E-cadherin and decrease ß-catenin expression, and reduce infiltration of M2 macrophages, thus inhibiting the process of colitis-to-cancer transition. Cell experiments revealed that BXD-containing serum can inhibit the proliferation, migration, and invasion of colon cancer cells infected with Fn and regulate their cell cycle. More importantly, we found that BXD-containing serum can inhibit the binding of Fn's FadA adhesin to E-cadherin, reduce Fn's attachment and invasion of colon cancer cells, thereby downregulating the E-cadherin/ß-catenin signaling pathway. CONCLUSIONS: These findings show that BXD can inhibit Fn colonization by interfering with the binding of FadA to E-cadherin, reducing the activation of the E-cadherin/ß-catenin signaling pathway, and ultimately delaying colitis-to-cancer transition.

[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.

Two microRNAs of plasma-derived small extracellular vesicles as biomarkers for metastatic non-small cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) of plasma-derived small extracellular vesicles (sEVs) have been proven to be associated with metastasis in several types of cancer. This study aimed to detect miRNAs of plasma-derived sEVs as potential biomarkers for metastatic non-small cell lung cancer (NSCLC). METHODS: We assessed the miRNA profiles of plasma-derived sEVs from healthy individuals as the control group (CT group), NSCLC patients without distant organ metastasis as the NM-NSCLC group and patients with distant organ metastasis as the M-NSCLC group. Next-generation sequencing (NGS) was performed on samples, and differentially expressed miRNAs (DEMs) of the three groups were screened. Kyoto Encyclopedia of Genes and Genomes (KEGG) and ClueGO were used to predict potential pathways of DEMs. MiRNA enrichment analysis and annotation tool (miEAA) was used to understand changes in the tumour microenvironment in NSCLC. Quantitative reverse transcription polymerase chain reaction (qRT‒PCR) analysis was used to validate target miRNAs. RESULT: NGS was performed on 38 samples of miRNAs of plasma-derived sEVs, and DEMs were screened out between the above three groups. Regarding the distribution of DEMs in the NM-NSCLC and M-NSCLC groups, KEGG pathway analysis showed enrichment in focal adhesion and gap junctions and ClueGO in the Rap1 and Hippo signaling pathways; miEAA found that fibroblasts were over-represented. From our screening, miRNA-200c-3p and miRNA-4429 were found to be predictive DEMs among the CT, NM-NSCLC and M-NSCLC groups, and qRT‒PCR was applied to verify the results. Finally, it was revealed that expression levels of miR-200c-3p and miR-4429 were significantly upregulated in M-NSCLC patients. CONCLUSION: This study identified miRNA-200c-3p and miRNA-4429 as potential biomarkers for NSCLC metastasis.

[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.

MiR-149-5p inhibits cell proliferation, promotes cell apoptosis and retards cell cycle of IL-22-stimulated HaCaT and NHEK keratinocytes via regulating PDE4D.

BACKGROUND: Psoriasis is a chronic autoimmune skin disease with unclear pathogenesis. It was found that miR-149-5p was significantly decreased in psoriatic lesion tissues. In this study, we aims to investigate the role and related molecular mechanism of miR-149-5p on psoriasis. METHOD: IL-22 was used to stimulate HaCaT and NHEK cells to establish psoriasis model in vitro. The miR-149-5p and phosphodiesterase 4D (PDE4D) expression levels were detected by quantitative real-time PCR. HaCaT and NHEK cells proliferation was determined by Cell Couting Kit-8 assay. The cell apoptosis and cell cycle were detected by flow cytometry. The cleaved Caspase-3, Bax and Bcl-2 protein expressions were detected by western blot. The targeting relationship between PDE4D and miR-149-5p was predicted and confirmed by Starbase V2.0 and dual-luciferase reporter assay, respectively. RESULT: There was a low expression level of miR-149-5p and a high expression of PDE4D in psoriatic lesion tissues. MiR-149-5p could target PDE4D. IL-22 promoted HaCaT and NHEK cells proliferation, while inhibited cell apoptosis and accelerated cell cycle. Moreover, IL-22 decreased the expressions of cleaved Caspase-3 and Bax, and increased the expression of Bcl-2. And the overexpressed miR-149-5p promoted HaCaT and NHEK cells apoptosis, inhibited cell proliferation and retarded cell cycle, meanwhile increased the cleaved Caspase-3 and Bax expressions, decreased the Bcl-2 expression. In addition, PDE4D overexpression has the opposite effect as miR-149-5p. CONCLUSION: The overexpressed miR-149-5p inhibits IL-22-stimulated HaCaT and NHEK keratinocytes proliferation, promotes cell apoptosis and retards cell cycle by down-regulating the expression of PDE4D, which could be the promising therapeutic target of psoriasis.

Pharmacologic effects approach of essential oils and their components on respiratory diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils (EOs) are concentrated hydrophobic liquids with volatility and a unique aroma. Formed by aromatic plants as secondary metabolites, EOs have been used as traditional medicines to treat various health problems worldwide. Historical records show that herbs rich in EOs have been widely used to treat respiratory diseases in China, Europe, and many other regions. AIM OF THE REVIEW: This review summarizes the traditional applications and modern pharmacological mechanisms of EOs derived from aromatic herbs and their active ingredients in respiratory diseases in preclinical and clinical trials through multitarget synergy. MATERIALS AND METHODS: Information about EOs and respiratory diseases was collected from electronic databases, such as ScienceDirect, Web of Science, PubMed, Google Scholar, Baidu Scholar, and the China National Knowledge Infrastructure (CNKI). RESULTS: This review presents the preventive and therapeutic effects of EOs on respiratory diseases, including chronic obstructive pulmonary disease, bronchial asthma, acute lung injury, pulmonary infection, and pulmonary fibrosis. The molecular mechanisms of EOs in treating different lung diseases are summarized, including anti-inflammation, anti-oxidation, mucolytic, and immune regulatory mechanisms. CONCLUSIONS: EOs show potential as supplements or substitutes for treating lung diseases.

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.

Brevilin A Ameliorates Acute Lung Injury and Inflammation Through Inhibition of NF-κB Signaling via Targeting IKKα/ß.

Acute lung injury (ALI) is life-threatening disease characterized by uncontrolled inflammatory response. IKKα/ß, the key kinases in the activation of NF-κB pathway, are implicated in inflammatory pulmonary injury, and represent attractive targets for ALI therapy. Brevilin A (BVA) is a sesquiterpene lactone from Centipeda minima, a Chinese herb used to treat inflammatory diseases. This study aims to investigate the inhibition of BVA on ALI, with focus on clarifying the molecular mechanisms involved in BVA-mediated anti-inflammatory activity in macrophages. Briefly, BVA significantly inhibited the production of NO and PGE2 by suppressing iNOS and COX2 expression, and suppressed the mRNA expression of IL-1ß, IL-6, and TNFα in LPS/IFNγ-stimulated RAW264.7 macrophages. The anti-inflammatory activity of BVA was further confirmed in LPS/IFNγ-stimulated BMDMs and TNFα/IFNγ-exposed RAW264.7 cells. In vivo, BVA effectively attenuated LPS-induced lung damage, inflammatory infiltration, and production of pro-inflammatory cytokines, including MPO, IL-1ß, IL-6, TNFα, and PGE2. Mechanistically, BVA could covalently bind to the cysteine 114 of IKKα/ß, and effectively inhibiting the activity and function of IKKα/ß, thereby resulting in the suppression of phosphorylation and degradation of IκBα and the subsequent activation of NF-κB signaling. Furthermore, pretreatment of DTT, a thiol ligand donor, significantly abolished BVA-mediated effects in LPS/IFNγ-stimulated RAW264.7 cells, suggesting the crucial role of the electrophilic α, ß-unsaturated ketone of BVA on its anti-inflammatory activity. These results suggest that BVA ameliorates ALI through inhibition of NF-κB signaling via covalently targeting IKKα/ß, raising the possibility that BVA could be effective in the treatment of ALI and other diseases harboring aberrant NF-κB signaling.

The molecular mechanism of chronic stress affecting the occurrence and development of breast cancer and potential drug therapy.

According to the 2020 data released by the International Agency for Research on Cancer, breast cancer has surpassed lung cancer as the world's most newly diagnosed first-time cancer. Compared with patients with other types of cancer, those with breast cancer experience greater mental stress and more severe psychological impacts because of the life-threatening diagnosis, physical changes, treatment side effects, and family and social life dysfunctions. These usually manifest as anxiety, depression, nervousness, and insomnia, all of which elicit stress responses. Particularly under chronic stress, the continuous release of neurotransmitters from the neuroendocrine system can have a highly profound impact on the occurrence and prognosis of breast cancer. However, because of the complex mechanisms underlying chronic stress and the variability in individual tolerance, evidence of the role of chronic stress in the occurrence and evolution of breast cancer remains unclear. This article reviewed previous research on the correlation between chronic stress and the occurrence and development of breast cancer, particularly the molecular mechanism through which chronic stress promotes breast cancer via neurotransmitters secreted by the nervous system. We also review the progress in the development of potential drugs or blockers for the treatment of breast cancer by targeting the neuroendocrine system.

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.

Deep Learning on MRI Images for Diagnosis of Lung Cancer Spinal Bone Metastasis.

This paper aimed to explore the adoption of deep learning algorithms in lung cancer spinal bone metastasis diagnosis. Comprehensive analysis was carried out with the aid of AdaBoost algorithm and Chan-Vese (CV) algorithm. 87 patients with lung cancer spinal bone metastasis were taken as research subjects, and comprehensive evaluation was made in terms of preliminary classification of images, segmentation results, Dice index, and Jaccard coefficient. After the case of misjudgment on whether there was hot spot was excluded, the initial classification accuracy of the AdaBoost algorithm can reach 96.55%. True positive rate (TPR) was 2.3%, and false negative rate (FNR) was 1.15%. 45 MRI images with hot spots were utilized as test set to detect the segmentation accuracy of CV, maximum between-cluster variance method (OTSU), and region growing algorithm. The results showed that the Dice index and Jaccard coefficient of the CV algorithm were 0.8591 and 0.8002, respectively, which were considerably superior to OTSU (0.6125 and 0.5541) and region growing algorithm (0.7293 and 0.6598). In summary, the AdaBoost algorithm was adopted for image preliminary classification, and CV algorithm for image segmentation was ideal for the diagnosis of lung cancer spinal bone metastasis and it was worthy of clinical promotion.

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.

Association of cardiovascular disease with 30-day hospital readmission in Chinese patients receiving maintenance dialysis.

BACKGROUND: Previous studies have shown cardiovascular disease (CVD) to be a risk factor in the prediction of 30-day hospital readmission among patients receiving dialysis. However, studies of Asian populations are limited. In the present study, we examined the association between CVD and 30-day hospital readmission in Chinese patients receiving maintenance dialysis. METHODS: Patients receiving maintenance dialysis were identified by searching a national claims database, the China Health Insurance Research Association (CHIRA) database, using the International Classification of Diseases revision 10 (ICD-10) and items of medical service claims. Patients aged ≥18 years who were discharged after index hospitalization between January 2015 and December 2015 were included in our retrospective analysis. CVD-related diagnoses were divided into three categories: coronary heart disease (CHD), heart failure (HF), and stroke. Thirty-day hospital readmission was defined as any hospital readmission within the 30 days following discharge. Logistic regression models adjusted for logit of propensity scores (PS) were used to assess the association of CVD with 30-day hospital readmission. RESULTS: Of 4,700 patients receiving dialysis, the 30-day hospital readmission rate was 10.4%. Compared with patients without CVD, there was an increased risk of 30-day hospital readmission among maintenance dialysis patients with total CVD [odds ratio (OR): 1.33, 95% confidence interval (CI): 1.06-1.66]. Patients with HF (OR: 1.77, CI: 1.27-2.47) and stroke (OR: 2.14, 95% CI: 1.53-2.98) had a greater risk of 30-day hospital readmission. The fully adjusted OR of CHD for the risk of 30-day hospital readmission was 1.22 (95% CI: 0.97-1.55). CONCLUSIONS: CVDs, especially stroke and HF, are independent predictors of 30-day hospital readmission in Chinese patients receiving dialysis, and could help to guide interventions to improve the quality of care for these patients.

Transferrin receptor regulates malignancies and the stemness of hepatocellular carcinoma-derived cancer stem-like cells by affecting iron accumulation.

BACKGROUND: Iron metabolism is essential because it plays regulatory roles in various physiological and pathological processes. Disorders of iron metabolism balance are related to various cancers, including hepatocellular carcinoma. Cancer stem-like cells (CSCs) exert critical effects on chemotherapy failure, cancer metastasis, and subsequent disease recurrence and relapse. However, little is known about how iron metabolism affects liver CSCs. Here, we investigated the expression of transferrin receptor 1 (TFR1) and ferroportin (FPN), two iron importers, and an upstream regulator, iron regulatory protein 2 (IRP2), in liver hepatocellular carcinoma (LIHC) and related CSCs. METHODS: The expression levels of TFR1, FPN and IRP2 were analysed using the GEPIA database. CSCs were derived from parental LIHC cells cultured in serum-free medium. After TFR1 knockdown, ROS accumulation and malignant behaviours were measured. The CCK-8 assay was performed to detect cell viability after TFR1 knockdown and erastin treatment. RESULTS: TFR1 expression was upregulated in LIHC tissue and CSCs derived from LIHC cell lines, prompting us to investigate the roles of TFR1 in regulating CSCs. Knockdown of TFR1 expression decreased iron accumulation and inhibited malignant behaviour. Knockdown of TFR1 expression decreased reactive oxygen species (ROS) accumulation induced by erastin treatment and maintained mitochondrial function, indicating that TFR1 is critical in regulating erastin-induced cell death in CSCs. Additionally, knockdown of TFR1 expression decreased sphere formation by decreasing iron accumulation in CSCs, indicating a potential role for TFR1 in maintaining stemness. CONCLUSION: These findings, which revealed TFR1 as a critical regulator of LIHC CSCs in malignant behaviour and stemness that functions by regulating iron accumulation, may have implications to improve therapeutic approaches.

2D-DOD and 2D-DOA Estimation for a Mixture of Circular and Strictly Noncircular Sources Based on L-Shaped MIMO Radar.

In this paper, a joint diagonalization based two dimensional (2D) direction of departure (DOD) and 2D direction of arrival (DOA) estimation method for a mixture of circular and strictly noncircular (NC) sources is proposed based on an L-shaped bistatic multiple input multiple output (MIMO) radar. By making full use of the L-shaped MIMO array structure to obtain an extended virtual array at the receive array, we first combine the received data vector and its conjugated counterpart to construct a new data vector, and then an estimating signal parameter via rotational invariance techniques (ESPRIT)-like method is adopted to estimate the DODs and DOAs by joint diagonalization of the NC-based direction matrices, which can automatically pair the four dimensional (4D) angle parameters and solve the angle ambiguity problem with common one-dimensional (1D) DODs and DOAs. In addition, the asymptotic performance of the proposed algorithm is analyzed and the closed-form stochastic Cramer-Rao bound (CRB) expression is derived. As demonstrated by simulation results, the proposed algorithm has outperformed the existing one, with a result close to the theoretical benchmark.