Improved temperature stability of a fiber Sagnac-like detection system for atomic magnetometers.

A novel fiber Sagnac-like detection system has unique competitive advantages for detecting atomic spin precession in atomic magnetometers. Unfortunately, its operating stability is severely limited by temperature fluctuations. In this paper, we describe a new approach to improve the temperature stability by using the ratio signal as the output instead of the conventional fundamental component. This method can effectively counteract the temperature-caused fluctuations in both light intensity and scale factor of photodetector. For a temperature range from 20°C to 40°C, a relative fluctuation of the ratio output signal of 0.97% was achieved, which was 17.4 times better than the fundamental component output. Moreover, no additional equipment and complex compensation algorithms are required during this process. It is a generic method that can also be applied to improve the stability of other detection schemes used in atomic magnetometers.

miR-129-5p and -3p co-target WWP1 to suppress gastric cancer proliferation and migration.

Gastric cancer (GC) is a worldwide health problem. Uncovering the underlining molecular mechanisms of GC is of vital significance. Here, we identified a novel oncogene WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) in GC. WWP1 could promote GC cell proliferation and migration in vitro and expedite GC growth in vivo. We also found out two microRNAs (miRNAs): miR-129-5p and -3p could both target WWP1. Interestingly, miR-129-5p bound to the CDS region of WWP1 mRNA. The miR-129 pairs (miR-129-5p and -3p) play pivotal roles in GC to suppress its proliferation and migration in vitro and slow down GC growth in vivo by repressing WWP1. In summary, we identified two tumor suppressive miRNAs which share the same precursor that could regulate the same oncogene WWP1 in GC. Our finding would add new route for GC research and treatment.

Effect of submucosal tunneling endoscopic resection for submucosal tumors at esophagogastric junction and risk factors for failure of en bloc resection.

BACKGROUND AND AIMS: Most submucosal tumors (SMTs) in the esophagogastric junction (EGJ) are irregularly shaped and different from those in the esophagus, where submucosal tunneling endoscopic resection (STER) has been proven effective and safe. However, few reports paid attention to STER for SMTs in the EGJ. The aim of the study was not only to evaluate the effect of STER in patients with SMTs in the EGJ but to analyze the risk factors for failure of en bloc resection. METHODS: A consecutive of 47 patients with SMTs originating from the muscularis propria (MP) layer in the EGJ underwent STER were retrospectively included between September 2012 and December 2016. Thirty-five tumors underwent en bloc resection, and the other 12 tumors received piecemeal resection. The tumor size, operation time, en bloc resection rate, complications, residual, and local recurrence were achieved and compared between the two groups. RESULTS: Forty-six of 47 lesions (97.9%) were successfully resected. The mean lesion size was 29.7 ± 16.3 mm. Both the en bloc resection rate and complete resection rate were 74.5% (35/47). No severe complications occurred in the 47 patients. Patients in the piecemeal resection group had more irregularly shaped lesions, longer tumor diameter, larger tumor size (≥40 mm), longer operation time, and longer hospital stay after procedure (P < 0.05), and there were no statistically differences between the two groups in in-operative complications, post-operative complications, and residual rate (P > 0.05). By univariate analysis and stepwise logistic regression analysis, irregular shape and tumor diameter ≥20 mm were two risk factors for failure of en bloc resection. CONCLUSIONS: STER is an effective and safe technique for the treatment of SMTs arising from the MP layer in the EGJ. Irregular shape and tumor diameter ≥20 mm are the reliable risk factors for en bloc resection failure.

Factors affecting the effectiveness and safety of submucosal tunneling endoscopic resection for esophageal submucosal tumors originating from the muscularis propria layer.

BACKGROUND AND AIMS: Submucosal tunneling endoscopic resection (STER) has been proved to be effective and safe for esophageal submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. This study was aimed to further evaluate the effectiveness, safety, and influencing factors especially the types of mucosal incision of STER in a larger population. METHODS: A total of 89 patients undergoing STER with esophageal SMTs were retrospectively enrolled in this study from May 2012 to November 2016. Clinicopathological, endoscopic, and adverse events (AEs) data were collected and analyzed. Different incision methods were compared to evaluate the optimum incision method. RESULTS: There were 27 females and 62 males with mean age of 46.5 ± 10.3 years. The medium size of the tumors was 16.0 mm (ranging 10.0-60.0 mm). Inverted T incisions were made in 29 (32.6%) patients, transverse incisions in 12 (13.5%) while longitudinal incisions in 48 (53.9%). En bloc resection was achieved in 70 (78.7%) patients. The residual rate was 1.1% (1/89), and no recurrence was noted even after piecemeal resection. The rate of AEs was 21.3% (19/89), and all of the AEs were cured without intervention or treated conservatively without the need for surgery. The en bloc resection rate was comparable among the three incision groups (P = 0.868); however, the incidence of AEs in the inverted T incision was lower than that in the longitudinal incision (P = 0.003). Fewer clips were used in the inverted T incision group than in the transverse incision group (P = 0.003). CONCLUSIONS: Although STER failed to achieve en bloc resection in 21.3% patients, it was still an effective therapy owing to low residual rate and no recurrence rate after piecemeal resection. STER was safe with no severe AEs; however, minor AEs were common. Inverted T incision seems to be the optimum entry point.

Insulated-tip knife endoscopic polypectomy for difficult pedunculated colorectal polyps: a prospective pilot study.

BACKGROUND: Endoscopic polypectomy is widely used for colorectal polyps. However, for giant pedunculated colorectal polyps (≥3 cm), conventional techniques are so difficult with en bloc resection that patients had to be transferred to surgery. We had firstly reported our first experience with an insulated-tip knife to successfully remove a giant pedunculated polyp in the sigmoid colon. In this study, our aim was to explore safety and feasible of insulated-tip knife endoscopic polypectomy (IT-EP) for difficult pedunculated colorectal polyps. METHODS: A total of seven consecutive patients with giant pedunculated colorectal polyps (≥3 cm) were prospectively enrolled. IT-EP was conducted with the help of clips for all the seven patients, and data of them was recorded and analyzed. RESULTS: Of seven patients, five were men and two were women with a mean age 61 years (49-72 years). The mean diameter of polyp head and stalk was 36.4 ± 4.9 mm (30-42 mm) and 14.6 ± 3.6 mm (10-20 mm), respectively. All the polyps were successfully removed with IT-EP, with a mean operation time of 14.9 ± 3.5 min (11-20 min). No serious bleeding or perforation was experienced, and no surgery was needed. There was no recurrence or residual of polyps at a mean 8.1-month follow-up. CONCLUSIONS: Insulated-tip knife endoscopic polypectomy is a safe and feasible alternative for difficult pedunculated colorectal polyps.

Upregulation of microRNA-31 targeting integrin α5 suppresses tumor cell invasion and metastasis by indirectly regulating PI3K/AKT pathway in human gastric cancer SGC7901 cells.

To verify the hypothesis that upregulation of microRNA-31 (miR-31) targeting integrin α5 (ITGA5) suppresses tumor cell invasion and metastasis by indirectly regulating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in human SGC7901 gastric cancer (GC) cells. The miRTarBase was used to predict whether ITGA5 is the target gene of miR-31, which was further confirmed by luciferase reporter gene assay. The SGC7901 GC cells were divided into five groups including the blank, miR-31 mimic, miR-31 mimic control, miR-31 inhibitor, and miR-31 inhibitor control groups. Reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting, cell scratch test, and transwell assays were respectively performed in our study. TGA5 was found as the target gene of miR-31. The RT-PCR detection revealed that, compared with the blank group, ITGA5 messenger RNA (mRNA) expression decreased in the miR-31 mimic group, but increased in the miR-31 inhibitor group. The western blotting examination suggested that the expressions of ITGA5, PI3K, and AKT proteins reduced in the miR-31 mimic group, but enhanced in the miR-31 inhibitor group when compared to the blank group, respectively. The cell scratch and transwell assays indicated that the miR-31 expressions were negatively associated with GC cell migration and invasion. Besides, RT-PCR combined with western blotting demonstrated that the miR-31 expressions were higher in the normal tissues than those in the GC tissues, while the ITGA5 mRNA and protein showed lower expression in the normal tissues than they did in the GC tissues. Our study concluded that upregulation of miR-31 targeting ITGA5 may suppress tumor cell invasion and metastasis by indirectly regulating PI3K/AKT signaling pathway in human SGC7901 GC cells.

Increased microRNA-223 in Helicobacter pylori-associated gastric cancer contributed to cancer cell proliferation and migration.

Dysregulation of microRNA-223 (miR-223) was associated with gastric cancer (GC), in which Helicobacter pylori (H. pylori) played important roles. However, the mechanism of relationships between miR-223 and H. pylori-associated GC was largely undiscovered. Here, we found the overexpression of miR-223 was related with H. pylori positive infection in vivo and in vitro in GC by relative quantification of qRT-PCR. Upregulated miR-223 was responsible for the poorer prognosis of GC with H. pylori positive, also. The result indicated not only overexpression of miR-223 stimulated the proliferation by CCK-8 assays and colony formation of H. pylori associated GC cells, but also migration and invasion by scratch assay and transwell invasion assays in vitro. Above all, all our data declared H. pylori infection played an important role in developing GC according to overexpression of miR-223, which increased cancer cell proliferation and migration.

[Changes of proliferation and angiogenesis of residual tumor in rabbit lung after radiofrequency ablation].

OBJECTIVE: To observe the changes of proliferation and angiogenesis of residual tumor in rabbit lung after radiofrequency ablation (RFA). METHODS: The model of VX2 tumor in rabbit lung was established by injection of tissue block suspension. 64 New Zealand White rabbits bearing VX2 tumor were assigned randomly to the control group (n = 10) and the RFA group (n = 48). During the RFA procedure, residual tumors were achieved by controlling the range of electrode expanding, output power and treatment time. At several points of time, Ki-67 labeling index (Ki-67LI) and microvessel density (MVD) of the residual tumors were calculated by immunohistochemical detection. RESULTS: Ki-67LI of the control group was 45.3% ± 2.1%. Ki-67LI of the RFA group at the first, 3 and 5 day were 56.4% ± 3.4%, 60.1% ± 4.1% and 59.8% ± 2.4% respectively, significantly higher than that of the control group; however, at the seventh, 9, 14 and 21 day, they were 45.4% ± 2.0%, 46.2% ± 3.4%, 45.1% ± 4.4% and 47.8% ± 3.9% respectively, no significant difference compared with the control group. The control group MVD was 28.9 ± 2.9. MVD of the RFA group at third, 5 and 7 day were 36.8 ± 2.6, 55.6 ± 4.8 and 51.5 ± 2.8 respectively, significantly higher than that of the control group; however, at the first, 9, 14 and 21 day were 27 ± 2.8, 29.2 ± 3.2, 30 ± 2.8 and 28.8 ± 3.1 respectively, no significant difference compared with the control group. CONCLUSIONS: The proliferation and angiogenesis of pulmonary residual tumor exhibit a transient increase phenomenon after RFA.

PANoptosis-related genes function as efficient prognostic biomarkers in colon adenocarcinoma.

Background: PANoptosis is a newly discovered cell death type, and tightly associated with immune system activities. To date, the mechanism, regulation and application of PANoptosis in tumor is largely unknown. Our aim is to explore the prognostic value of PANoptosis-related genes in colon adenocarcinoma (COAD). Methods: Analyzing data from The Cancer Genome Atlas-COAD (TCGA-COAD) involving 458 COAD cases, we concentrated on five PANoptosis pathways from the Molecular Signatures Database (MSigDB) and a comprehensive set of immune-related genes. Our approach involved identifying distinct genetic COAD subtype clusters and developing a prognostic model based on these parameters. Results: The research successfully identified two genetic subtype clusters in COAD, marked by distinct profiles in PANoptosis pathways and immune-related gene expression. A prognostic model, incorporating these findings, demonstrated significant predictive power for survival outcomes, underscoring the interplay between PANoptosis and immune responses in COAD. Conclusion: This study enhances our understanding of COAD's genetic framework, emphasizing the synergy between cell death pathways and the immune system. The development of a prognostic model based on these insights offers a promising tool for personalized treatment strategies. Future research should focus on validating and refining this model in clinical settings to optimize therapeutic interventions in COAD.

An effective prognostic model in colon adenocarcinoma composed of cuproptosis-related epigenetic regulators.

Background: Colorectal adenocarcinoma (COAD) is a common malignant tumor with little effective prognostic markers. Cuproptosis is a newly discovered mode of cell death that may be related to epigenetic regulators. This study aimed to explore the association between epigenetic regulators and cuproptosis, and to establish a prognostic prediction model for COAD based on epigenetic regulators associated with cuproptosis (EACs). Methods: RNA sequencing data and clinical data of 524 COAD patients were obtained from the TCGA-COAD database, cuproptosis-related genes were from the FerrDb database, and epigenetic-related genes were from databases such as GO and EpiFactors. LASSO regression analysis and other methods were used to screen out epigenetic regulators associated with cuproptosis and prognosis. The risk score of each patient was calculated and the patients were divided into high-risk group and low-risk group. Next, the survival difference, functional enrichment analyses, tumor mutation burden, chemotherapy drug sensitivity and other indicators between the two groups were compared and analyzed. Results: We found 716 epigenetic regulators closely related to cuproptosis, among which 35 genes were related to prognosis of COAD. We further screened out 7 EACs from the 35 EACs to construct a prognostic prediction model. We calculated the risk score of each patient based on these 7 genes, and divided the patients into high-risk group and low-risk group. We found that the overall survival rate and progression-free survival rate of the high-risk group were significantly lower than those of the low-risk group. This model showed good predictive ability in the training set, test set and overall data set. We also constructed a prognostic prediction model based on risk score and other clinical features, and drew the corresponding Nomogram. In addition, we found significant differences between the high-risk group and the low-risk group in tumor mutation burden, chemotherapy drug sensitivity and other clinical aspects. Conclusion: We established an effective predictive prediction model for COAD based on EACs, revealing the association between epigenetic regulators and cuproptosis in COAD. We hope that this model can not only facilitate the treatment decision of COAD patients, but also promote the research progress in the field of cuproptosis.

A new ferroptosis-related signature model including messenger RNAs and long non-coding RNAs predicts the prognosis of gastric cancer patients.

Background and Objectives: Gastric cancer (GC) is among the most malignant tumor types, which causes heavy healthy and economic burden to the people and societies all around the world. Establishment of an effective set of prognostic marker will benefit a lot to the treatment of GC patients clinically. Ferroptosis is a newly identified regulated cell death modality, with tight relevance with GC development. However, its application in the prognosis of GC has not been studied in detail. Deregulated messenger RNA (mRNA) and long non-coding RNA (lncRNA) expression profile in tumor can serve as novel prognostic marker for predicting the survival and cancer relapse in patients. Methods: We downloaded ferroptosis-related gene expression microarray data, clinicopathologic information and a list of 259 ferroptosis-related genes from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Ferroptosis database, respectively. Then, correlation analysis, univariate and multivariate Cox regression analysis were used to construct a novel prognostic model for GC. Then, we validated the model in the GEO datasets. Finally, we evaluated the differences in immune microenvironment between high- and low-risk groups. Results: We utilized the ferroptosis-related mRNA and lncRNA profile to successfully construct a prognostic model (incorporating 2 mRNAs and 15 lncRNAs) in GC. Our model, integrating diverse clinical traits and critical factors of GC, showed desirable efficacy in the prognosis of GC patients. This model also manifested effectively in validation by using external patients' data. Conclusions: Our study developed a novel ferroptosis-related signature to predict the prognosis of gastric cancer patients. The ferroptosis-related signature had a favorable predictive ability. This model may greatly boost the treatment of GC patients in clinical practice.

Multifunctional metal-organic framework (MOF)-based nanoplatforms for cancer therapy: from single to combination therapy.

Cancer remains a severe threat to human health. To date, although various therapeutic methods, including radiotherapy (RT), chemotherapy, chemodynamic therapy (CDT), phototherapy, starvation therapy, and immunotherapy, have entered a new stage of rapid progress in cancer theranostics, their limited therapeutic effect and significant side effects need to be considered carefully. With the rapid development of nanotechnology, the marriage of nanomaterials and therapeutic methods provides the practical possibility to improve the deficiencies in cancer therapy. Notably, metal-organic frameworks (MOFs) composed of ions/clusters and bridging ligands through coordination bonds have been widely applied in cancer therapy to deal with the drawbacks of different therapeutic methods, such as severe side effects, low stability, and poor efficacy, owing to their controllable morphologies, tailorable diameters, diverse compositions, tunable porosities, high specific surface areas, facile functionalization, and good biocompatibility. This review summarizes the recent advanced developments and achievements of multifunctional MOF-based nanoplatforms for cancer therapy through single therapy methods, including RT, chemotherapy, CDT, phototherapy (photodynamic and photothermal therapy), starvation therapy and immunotherapy, and combination therapy methods. Moreover, the prospects and challenges of MOF-based nanoplatforms used in tumor therapy are also discussed.

Identification of PTPN20 as an innate immunity-related gene in gastric cancer with Helicobacter pylori infection.

Background: Gastric cancer (GC) is among the deadliest diseases with countless incidences and deaths each year. Helicobacter pylori (Hp) is the primary type of microbe that colonizes the stomach. In recent years, increasing evidence has demonstrated that Hp infection is one of the main risk factors for GC. Elucidating the molecular mechanism of how Hp leads to GC will not only benefit the treatment of GC, but also boost the development of therapeutics for other gastric disorders caused by Hp infection. In this study, we aimed to identify innate immunity-related genes in GC and investigate their potentials as prognostic markers and therapeutic targets for Hp-related GC. Methods: Firstly, we analyzed the differentially expressed innate immunity-related genes in GC samples from the TCGA database. Then prognostic correlation analysis was carried out to explore the prognostic value of these candidate genes. By combing transcriptome data, somatic mutation data, and clinical data, co-expression analysis, functional enrichment analysis, tumor mutational burden analysis, and immune infiltration analysis were performed to reveal the pathological relevance of the candidate gene. Finally, ceRNA network was constructed to identify the genes and pathways for the regulation of the candidate gene. Results: We revealed that protein tyrosine phosphatase non-receptor type 20 (PTPN20) is a significant prognostic marker in Hp-related GC. Thus, PTPN20 levels have the potential to efficiently predict the survival of Hp-related GC patients. In addition, PTPN20 is associated with immune cell infiltration and tumor mutation burden in these GC patients. Moreover, we have also identified PTPN20-related genes, PTPN20 protein-protein interactions, and the PTPN20 ceRNA network. Conclusion: Our data suggest that PTPN20 may have critical functions in Hp-related GC. Targeting PTPN20 may be a promising way to treat Hp-related GC.

Local injection of adipose-derived mesenchymal stem cells in silk fibroin solution on the regeneration of lower esophageal sphincter in an animal model of GERD.

Presently, various tissue engineering methods using adult stem cells and biomaterials are being confirmed to regenerate vessels, cardiac muscle, bladder, and intestines. However, there are few studies about the repair of the lower esophageal sphincter (LES) may help alleviate the symptoms of gastroesophageal reflux disease (GERD). This study aims to determine whether Adipose-Derived Stem Cells (ADSCs) combined with regenerated silk fibroin (RSF) solution could regenerate the LES. In vitro, the ADSCs were isolated, identified, and then cultured with an established smooth muscular induction system. In vivo, in the experimental groups, CM-Dil labeled ADSCs or induced ADSCs mixed with RSF solution were injected into the LES of rats after the development of the animal model of GERD respectively. The results showed that ADSCs could be induced into smooth muscular-like cells with the expression of h-caldesmon, calponin, α-smooth muscle actin, and a smooth muscle-myosin heavy chain in vitro. In vivo, the thickness of LES in the experiment rats was much thicker than those in the controlled groups. This result indicated that ADSCs mixed with RSF solution might contribute to the regeneration of the LES, thus reducing the occurrence of GERD.

Identification of Hub Genes in Colorectal Adenocarcinoma by Integrated Bioinformatics.

An improved understanding of the molecular mechanism of colorectal adenocarcinoma is necessary to predict the prognosis and develop new target gene therapy strategies. This study aims to identify hub genes associated with colorectal adenocarcinoma and further analyze their prognostic significance. In this study, The Cancer Genome Atlas (TCGA) COAD-READ database and the gene expression profiles of GSE25070 from the Gene Expression Omnibus were collected to explore the differentially expressed genes between colorectal adenocarcinoma and normal tissues. The weighted gene co-expression network analysis (WGCNA) and differential expression analysis identified 82 differentially co-expressed genes in the collected datasets. Enrichment analysis was applied to explore the regulated signaling pathway in colorectal adenocarcinoma. In addition, 10 hub genes were identified in the protein-protein interaction (PPI) network by using the cytoHubba plug-in of Cytoscape, where five genes were further proven to be significantly related to the survival rate. Compared with normal tissues, the expressions of the five genes were both downregulated in the GSE110224 dataset. Subsequently, the expression of the five hub genes was confirmed by the Human Protein Atlas database. Finally, we used Cox regression analysis to identify genes associated with prognosis, and a 3-gene signature (CLCA1-CLCA4-GUCA2A) was constructed to predict the prognosis of patients with colorectal cancer. In conclusion, our study revealed that the five hub genes and CLCA1-CLCA4-GUCA2A signature are highly correlated with the development of colorectal adenocarcinoma and can serve as promising prognosis factors to predict the overall survival rate of patients.

Development and validation of cuproptosis-related gene signature in the prognostic prediction of liver cancer.

Liver cancer is a generic term referring to several cancer types arising from the liver. Every year, liver cancer causes lots of deaths and other burdens to the people all over the world. Though the techniques in the diagnosis and therapy of liver cancer have undergone significant advances, the current status of treating liver cancer is not satisfactory enough. The improvement of techniques for the prognosis of liver cancer patients will be a great supplement for the treatment of liver cancer. Cuproptosis is a newly identified regulatory cell death type, which may have a close connection to liver cancer pathology. Here, we developed a prognostic model for liver cancer based on the cuproptosis-related mRNAs and lncRNAs. This model can not only effectively predict the potential survival of liver cancer patients, but also be applied to evaluate the infiltration of immune cell, tumor mutation burden, and sensitivity to anti-tumor drugs in liver cancer. In addition, this model has been successfully validated in lots of liver cancer patients' data. In summary, we wish this model can become a helpful tool for clinical use in the therapy of liver cancer.

Analysis of the correlation between non-alcoholic fatty liver disease and the risk of colorectal neoplasms.

This study aims at assessing the potential association between non-alcoholic fatty liver disease (NAFLD) and colorectal neoplasms (CRN). PubMed, Cochrane Library, and Embase were searched for cohort studies. 14 cohort studies with a total population of 38,761,773 were included for meta-analysis after selection. The results showed that NAFLD is related to an increased risk of CRN (OR = 1.23; 95% CI: 1.14-1.32; I2 = 70.7%, p < 0.001). In the subgroup analysis, NAFLD were found to be the independent risk factor of colorectal adenoma (CRA) (OR = 1.29; 95% CI = 1.15-1.45; I2 = 66.4%) and colorectal cancer (CRC) (OR = 1.13; 95% CI = 1.12-1.15; I2 = 69.4%). There is no close correlation between smoking status of NAFLD patients and CRN. Interestingly, bioinformatics analysis revealed that there were overlap of dysregulated gene sets among NAFLD, CRC, and two recently identified regulated cell death types, ferroptosis and cuproptosis, respectively. Our meta- and bioinformatics analysis shows that NAFLD increases the risk of CRN. Ferroptosis and cuproptosis may be the critical links between NAFLD and CRN, respectively. These findings here support that NAFLD is necessary to be considered as an emerging risk factor for CRN.

Erratum.

Colon cancer is one of the most lethal varieties of cancer. Chemotherapy remains as one of the principal treatment approaches for colon cancer. The anticancer activity of procaine (PCA), which is a local anesthetic drug, has been explored in different studies. In our study, we aimed to explore the anticancer effect of PCA on colon cancer and its underlying mechanism. The results showed that PCA significantly inhibited cell viability, increased the percentage of apoptotic cells, and decreased the expression level of RhoA in HCT116 cells in a dose-dependent manner (p<0.05 or p<0.01). Moreover, PCA increased the proportion of HCT116 cells in the G1 phase as well as downregulated cyclin D1 and cyclin E expressions (p<0.05). In addition, we found that PCA remarkably inhibited cell migration in HCT116 cells (p<0.01). However, all these effects of PCA on cell proliferation, apoptosis, and migration were significantly reversed by PCA+pc-RhoA (p<0.05 or p<0.01). PCA also significantly decreased the levels of p-ERK, p-p38MAPK, and p-FAK, but PCA+pc-RhoA rescued these effects. Furthermore, the ERK inhibitor (PD098059), p38MAPK inhibitor (SB203580), and FAK inhibitor (Y15) reversed these results. These data indicate that PCA inhibited cell proliferation and migration but promoted apoptosis as well as inactivated the ERK/MAPK/FAK pathways by regulation of RhoA in HCT116 cells.

Efficacy and Safety of Peroral Endoscopic Myotomy for Sigmoid-Type Achalasia: A Systematic Review and Meta-Analysis.

Background: The efficacy and safety of peroral endoscopic myotomy (POEM) in the treatment of sigmoid-type achalasia is unknown. This meta-analysis aims to explore the clinical outcomes of POEM for sigmoid-type achalasia. Method: We searched all relevant studies published up to September 2020 in PubMed, Embase, and Cochrane library databases. Meta-analyses for clinical success, Eckardt score, angle of esophageal tortuosity, diameter of esophagus, lower esophageal sphincter (LES) pressure, integrated relaxation pressure (IRP), adverse events, and gastroesophageal reflux diseases were performed based on random or fixed-effects models as needed. Results: We found a total of eight studies that provided data on 248 patients. Overall, the pooled clinical success was achieved in 211 sigmoid-type achalasia patients [90.4%; 95% confidence interval (CI), 85.5%-93.8%]. The pre- and post-POEM Eckardt scores, angle of esophageal tortuosity, diameter of esophageal, LES pressure, and IRP were significantly improved (All p < 0.05). The pooled adverse events rate was 13.0% (95% CI, 3.6%-37.4%). The pooled objective confirmation of reflux rate was 41.5% (95% CI, 26.5%-58.3%), and symptomatic reflux rate was 12.5% (95% CI, 8.3%-18.4%). Conclusions: Our current evidence indicated that POEM is an effective and safe therapeutic modality for the treatment of sigmoid-type achalasia.

Supramolecular nanomaterials based on hollow mesoporous drug carriers and macrocycle-capped CuS nanogates for synergistic chemo-photothermal therapy.

Multifunctional supramolecular nanoplatforms that integrate the advantages of different therapeutic techniques can trigger multimodal synergistic treatment of tumors, thus representing an emerging powerful tool for cancer therapeutics. Methods: In this work, we design and fabricate a multifunctional supramolecular drug delivery platform, namely Fa-mPEG@CP5-CuS@HMSN-Py nanoparticles (FaPCH NPs), consisting of a pyridinium (Py)-modified hollow mesoporous silica nanoparticles-based drug reservoir (HMSN-Py) with high loading capacity, a layer of NIR-operable carboxylatopillar[5]arene (CP5)-functionalized CuS nanoparticles (CP5-CuS) on the surface of HMSN-Py connected through supramolecular host-guest interactions between CP5 rings and Py stalks, and another layer of folic acid (Fa)-conjugated polyethylene glycol (Fa-PEG) antennas by electrostatic interactions capable of active targeting at tumor lesions, in a controlled, highly integrated fashion for synergistic chemo-photothermal therapy. Results: Fa-mPEG antennas endowed the enhanced active targeting effect toward cancer cells, and CP5-CuS served as not only a quadruple-stimuli responsive nanogate for controllable drug release but also a special agent for NIR-guided photothermal therapy. Meanwhile, anticancer drug doxorubicin (DOX) could be released from the HMSN-Py reservoirs under tumor microenvironments for chemotherapy, thus realizing multimodal synergistic therapeutics. Such a supramolecular drug delivery platform showed effective synergistic chemo-photothermal therapy both in vitro and in vivo. Conclusion: This novel supramolecular nanoplatform possesses great potential in controlled drug delivery and tumor cellular internalization for synergistic chemo-photothermal therapy, providing a promising approach for multimodal synergistic cancer treatment.