Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling.

BACKGROUND: Altered miR-188-3p expression has been observed in various human cancers. AIM: To investigate the miR-188-3p expression, its roles, and underlying molecular events in gastric cancer. METHODS: Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression. Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays. The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay. A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival. A nude mouse tumor cell xenograft assay was used to confirm the in vitro data. RESULTS: MiR-188-3p was found to be lower in the plasma of gastric cancer patients, tissues, and cell lines compared to their healthy counterparts. It was associated with overall survival of gastric cancer patients (P < 0.001), tumor differentiation (P < 0.001), lymph node metastasis (P = 0.033), tumor node metastasis stage (I/II vs III/IV, P = 0.024), and American Joint Committee on Cancer stage (I/II vs III/IV, P = 0.03). Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy. CBL was identified as a direct target of miR-188-3p, with its expression antagonizing the effects of miR-188-3p on gastric cancer (GC) cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway. The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer. CONCLUSION: The current data provides ex vivo, in vitro, and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.

Prognostic value of long non-coding RNA MALAT1 in hepatocellular carcinoma: A study based on multi-omics analysis and RT-PCR validation.

Background: This study aimed to explore the relationship between MALAT1 and the prognosis of patients with hepatocellular carcinoma (HCC). Methods: We constructed a MALAT1 protein-protein interaction network using the STRING database and a network of competing endogenous RNAs (ceRNAs) using the StarBase database. Using data from the GEPIA2 database, we studied the association between genes in these networks and survival of patients with HCC. The potential mechanisms underlying the relationship between MALAT1 and HCC prognosis were studied using combined data from RNA sequencing, DNA methylation, and somatic mutation data from The Cancer Genome Atlas (TCGA) liver cancer cohort. Tumor tissues and 19 paired adjacent non-tumor tissues (PANTs) from HCC patients who underwent radical resection were analyzed for MALAT1 mRNA levels using real-time PCR, and associations of MALAT1 expression with clinicopathological features or prognosis of patients were analyzed using log-rank test and Gehan-Breslow-Wilcoxon test. Results: Five interacting proteins and five target genes of MALAT1 in the ceRNA network significantly correlated with poor survival of patients with HCC (p < 0.05). High MALAT1 expression was associated with mutations in two genes leading to poor prognosis and may upregulate some prognostic risk genes through methylation. MALAT1 was significantly co-expressed with various signatures of genes involved in HCC progression, including the cell cycle, DNA damage repair, mismatch repair, homologous recombination, molecular cancer m6A, exosome, ferroptosis, infiltration of lymphocyte (p < 0.05). The expression of MALAT1 was markedly upregulated in HCC tissues compared with PANTs. In Kaplan-Meier analysis, patients with high MALAT1 expression had significantly shorter progression-free survival (PFS) (p = 0.033) and overall survival (OS) (p = 0.023) than those with low MALAT1 expression. Median PFS was 19.2 months for patients with high MALAT1 expression and 52.8 months for patients with low expression, while the corresponding median OS was 40.5 and 78.3 months. In subgroup analysis of patients with vascular invasion, cirrhosis, and HBsAg positive or AFP positive, MALAT1 overexpression was significantly associated with shorter PFS and OS. Models for predicting PFS and OS constructed based on MALAT1 expression and clinicopathological features had moderate predictive power, with areas under the receiver operating characteristic curves of 0.661-0.731. Additionally, MALAT1 expression level was significantly associated with liver cirrhosis, vascular invasion, and tumor capsular infiltration (p < 0.05 for all). Conclusion: MALAT1 is overexpressed in HCC, and higher expression is associated with worse prognosis. MALAT1 mRNA level may serve as a prognostic marker for patients with HCC after hepatectomy.

The comparison of different drip cholangiography: a randomised trial.

BACKGROUND: This study investigated the advantages and disadvantages of contrast media administration by gravity drip and manual push injection during cholangiography. METHODS: A total of 100 patients who presented to the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, for a cholangiography between June 2019 to June 2020 were enrolled in this study. Patients were randomly divided into 2 treatment groups. One group of patients with manual injection of contrast (the N group, n=50), received the contrast agent via the traditional manual injection method whereby the doctor injects 50 mL of prepared contrast agent into the right side of the patient while continuously observing the effects on the bile duct. The other group of patients with gravity drip administration of contrast media (the O group, n=50), received the contrast agent via gravity drip at a rate of 80 drops per minute, and both clinicians and radiologists monitored the entire cholangiography process from a safe distance. Patients were followed up and angiographic satisfaction was assessed after two weeks. RESULTS: All 100 patients completed cholangiography without allergic reaction to the contrast medium. In the traditional injection group (N group), nine patients experienced upper abdominal discomfort with nausea, abdominal pain, chills, high fever, and other symptoms, and residual gallstones were observed in 12 patients. In patients in the gravity drip group (O group), four patients felt upper abdominal discomfort accompanied by nausea, abdominal pain, chills, high fever, and other symptoms, with residual gallstones detected in six patients. CONCLUSIONS: Patients who underwent gravity drip cholangiography had significantly reduced adverse reactions compared to patients who underwent traditional manual infusion cholangiography. Furthermore, gravity drip cholangiography resulted in clearer images and reduced X-ray exposure for medical staff. Thus, increased implementation of gravity drip cholangiography in the clinical setting should be considered. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018202.

Intestinal microbiota: A potential target for enhancing the antitumor efficacy and reducing the toxicity of immune checkpoint inhibitors.

Accumulating evidence suggests that the intestinal microbiota is associated with the antitumor efficacy of immune checkpoint inhibitors (ICIs) and the occurrence of immune-related adverse events (irAEs) following ICI treatment. However, the mechanisms underlying these interactions remain unclear. Recent technological advances have allowed more extensive investigation into the interplay between the intestinal microbiota and the tumor immune microenvironment. Breakthroughs by two research groups revealed that Bifidobacterium enhanced the efficacy of ICIs via the stimulator of interferon genes (STING) and adenosine 2A receptor (A2AR) signaling pathways, highlighting the molecular mechanisms through which the intestinal microbiota modulates immunotherapy. In this review, we summarize recent findings related to the potential role and mechanisms of the gut microbiota in ICI therapy, available microbiota-targeting strategies, and ongoing clinical trials. Further we discuss the associated challenges that remain in this field of research. The current review aims to evaluate the potential of the intestinal microbiota in maximizing the antitumor efficacy of ICIs while minimizing their toxic effects and guiding the development of more specific treatment regimens.

The lumbar autonomic nerves in males: a few anatomical insights into anterior lumbar interbody fusion.

BACKGROUND CONTEXT: Lumbar autonomic nerve injury is an underappreciated complication of anterior lumbar spinal surgery. A detailed description of lumbar autonomic nerve anatomy would be helpful for surgeons to minimize the risk of this complication. PURPOSE: This study was designed to investigate the anatomical characteristics of lumbar autonomic nerves and provide a better understanding of these nerves for anterior lumbar spinal surgery. STUDY DESIGN: A dissection-based study of 10 embalmed male cadavers. METHODS: The lumbar autonomic nerves from 10 embalmed male cadavers were dissected in this study. The position of the lumbar sympathetic trunks was recorded. Distance between the initial sites of the lumbar splanchnic nerves (LSNs) and the corresponding lumbar vertebral inferior endplate, distance between the ipsilateral and adjacent LSNs, angles formed by the LSNs and the vertical axis were measured. This study has been supported by grants from Science and Technology Planning Project of Guangdong Province (CN) (Grant No. 2017B020210010) without potential conflict of interest-associated biases in the text of the paper. RESULTS: In this study, a total of 72 LSNs were identified in the 10 human cadavers. On average, the investigation found that the initial sites of the first, second, third, and fourth LSNs were 9 mm distal, 5 mm distal, 9 mm proximal, and 9 mm distal to the inferior endplates of the L1, L2, L3, and L4 vertebrae, respectively, with variations from 6 to 11 mm for each nerve among specimens. There was no significant difference in the angle between each lumbar splanchnic nerve and the vertical axis (H=2.461, p=.482), with an angle of approximately 50°±6°. The distance between the first and the second LSNs, the second and the third LSNs, or the third and the fourth LSNs were 24±6 mm, 22±8 mm, and 55±11 mm, respectively. The bilateral lumbar sympathetic trunks (N=57, 95%) were more likely to be located in the first third of the sagittal plane at the level of the L2/3, L3/4, and L4/5 intervertebral discs. CONCLUSIONS: The study found the same number and parallel courses of LSNs on each side, and on both the left and right side, the distance between the third and the fourth LSNs was much larger than the distance between the other two adjacent LSNs. The initial sites of 80.6% (n=58) of LSNs were superior to the inferior endplate of the L3 vertebra. Improved knowledge of lumbar autonomic nerve anatomy may be of great significance in reducing complications and improving surgical safety.

Ultrabroad supercontinuum generated from a highly nonlinear Ge-Sb-Se fiber.

We report the fabrication of a novel high nonlinear fiber made of Ge-Sb-Se chalcogenide glasses with high numerical aperture (∼1.0), where the core and the cladding glasses consist of Ge15Sb25Se60 and Ge15Sb20Se65 (mol. %), respectively. The nonlinear refractive index (n2) of the core glass is 19×10-18 m2/W at 1.55 µm, and its laser-induced damage threshold under irradiation of 3.0 µm fs laser is approximately 3674 GW/cm2. By pumping a 20-cm-long fiber with a core diameter of 23 µm using 150 fs pulses at 6.0 µm, supercontinuum spanning from ∼1.8 to ∼14 µm was generated.

Acupuncture for Pain Management in Cancer: A Systematic Review and Meta-Analysis.

Objective. To evaluate the effectiveness and safety of acupuncture for cancer-related pain. Methods. A systematic review of literatures published from database inception to February 2015 was conducted in eight databases. RCTs involving acupuncture for treatment of cancer-related pain were identified. Two researchers independently performed article selection, data extraction, and quality assessment of data. Results. 1,639 participants in twenty RCTs were analyzed. All selected RCTs were associated with high risk of bias. Meta-analysis indicated that acupuncture alone did not have superior pain-relieving effects as compared with conventional drug therapy. However, as compared with the drug therapy alone, acupuncture plus drug therapy resulted in increased pain remission rate, shorter onset time of pain relief, longer pain-free duration, and better quality of life without serious adverse effects. However, GRADE analysis revealed that the quality of all outcomes about acupuncture plus drug therapy was very low. Conclusions. Acupuncture plus drug therapy is more effective than conventional drug therapy alone for cancer-related pain. However, multicenter high-quality RCTs with larger sample sizes are needed to provide stronger evidence for the effectiveness of acupuncture in cancer-related pain due to the low data quality of the studies included in the current meta-analysis.

Inhibition of autophagy enhances the radiosensitivity of nasopharyngeal carcinoma by reducing Rad51 expression.

Radiotherapy has long been considered as the mainstay of treatment for nasopharyngeal carcinoma (NPC). However, locoregional recurrence or distant metastasis may occur in some patients due to the radiation resistance of cancer cells. Autophagy plays a vital role in protecting cells against radiation. However, the mechanism of autophagy in radiation therapy remains obscure. In the present study, we demonstrated that suppression of autophagy related 5 (Atg5) aggravated ionizing radiation (IR)-induced DNA damage and apoptosis in human NPC cells without accelerating the cell cycle, whereas regulation of the cell cycle has been widely regarded as the most important determinant of IR sensitivity. Further study showed that inhibition of autophagy suppressed the mRNA expression of Rad51, a key protein of homologous recombination that has been demonstrated to play a critical role in the repair of DNA double-strand breaks induced by radiation. Moreover, suppression of Atg5 had no impact on the radiosensitivity when cells were pre-treated by the Rad51 inhibitor, and the enhanced radiosensitivity by Atg5 suppression was reversed by overexpression of Rad51 in human NPC cells. Our results suggest that inhibition of autophagy enhances the susceptibility of NPC cells to radiation by reducing Rad51 expression. Therefore, Rad51 targeted therapy may be investigated as a potential novel agent for the adjuvant treatment of traditional radiation of NPC.