Analysis of quality of life in patients after transgastric natural orifice transluminal endoscopic gallbladder-preserving surgery.

BACKGROUND: At present, laparoscopic cholecystectomy (LC) is the main surgical treatment for gallstones. But, after gallbladder removal, there are many complications. Therefore, it is hoped to remove stones while preserving the function of the gallbladder, and with the development of endoscopic technology, natural orifice transluminal endoscopic surgery came into being. AIM: To compare the quality of life, perioperative indicators, adverse events after LC and transgastric natural orifice transluminal endoscopic gallbladder-preserving surgery (EGPS) in patients with gallstones. METHODS: Patients who were admitted to The First Affiliated Hospital of Xinjiang Medical University from 2020 to 2022 were retrospectively collected. We adopted propensity score matching (1:1) to compare EGPS and LC patients. RESULTS: A total of 662 cases were collected, of which 589 cases underwent LC, and 73 cases underwent EGPS. Propensity score matching was performed, and 40 patients were included in each of the groups. In the EGPS group, except the gastrointestinal defecation (P = 0.603), the total score, physical well-being, mental well-being, and gastrointestinal digestion were statistically significant compared with the preoperative score after surgery (P < 0.05). In the LC group, except the mental well-being, the total score, physical well-being, gastrointestinal digestion, the gastrointestinal defecation was statistically significant compared with the preoperative score after surgery (P < 0.05). When comparing between groups, gastrointestinal defecation had significantly difference (P = 0.002) between the two groups, there was no statistically significant difference in the total postoperative score and the other three subscales. In the surgery duration, hospital stay and cost, LC group were lower than EGPS group. The recurrence factors of gallstones after EGPS were analyzed: and recurrence was not correlated with gender, age, body mass index, number of stones, and preoperative score. CONCLUSION: Whether EGPS or LC, it can improve the patient's symptoms, and the EGPS has less impact on the patient's defecation. It needed to, prospective, multicenter, long-term follow-up, large-sample related studies to prove.

Predictive factors and model validation of post-colon polyp surgery Helicobacter pylori infection.

BACKGROUND: Recently, research has linked Helicobacter pylori (H. pylori) stomach infection to colonic inflammation, mediated by toxin production, potentially impacting colorectal cancer occurrence. AIM: To investigate the risk factors for post-colon polyp surgery, H. pylori infection, and its correlation with pathologic type. METHODS: Eighty patients who underwent colon polypectomy in our hospital between January 2019 and January 2023 were retrospectively chosen. They were then randomly split into modeling (n = 56) and model validation (n = 24) sets using R. The modeling cohort was divided into an H. pylori-infected group (n = 37) and an H. pylori-uninfected group (n = 19). Binary logistic regression analysis was used to analyze the factors influencing the occurrence of H. pylori infection after colon polyp surgery. A roadmap prediction model was established and validated. Finally, the correlation between the different pathological types of colon polyps and the occurrence of H. pylori infection was analyzed after colon polyp surgery. RESULTS: Univariate results showed that age, body mass index (BMI), literacy, alcohol consumption, polyp pathology type, high-risk adenomas, and heavy diet were all influential factors in the development of H. pylori infection after intestinal polypectomy. Binary multifactorial logistic regression analysis showed that age, BMI, and type of polyp pathology were independent predictors of the occurrence of H. pylori infection after intestinal polypectomy. The area under the receiver operating characteristic curve was 0.969 [95% confidence interval (95%CI): 0.928-1.000] and 0.898 (95%CI: 0.773-1.000) in the modeling and validation sets, respectively. The slope of the calibration curve of the graph was close to 1, and the goodness-of-fit test was P > 0.05 in the two sets. The decision analysis curve showed a high rate of return in both sets. The results of the correlation analysis between different pathological types and the occurrence of H. pylori infection after colon polyp surgery showed that hyperplastic polyps, inflammatory polyps, and the occurrence of H. pylori infection were not significantly correlated. In contrast, adenomatous polyps showed a significant positive correlation with the occurrence of H. pylori infection. CONCLUSION: Age, BMI, and polyps of the adenomatous type were independent predictors of H. pylori infection after intestinal polypectomy. Moreover, the further constructed column-line graph prediction model of H. pylori infection after intestinal polypectomy showed good predictive ability.

Circ_0003789 Knockdown Inhibits Tumor Progression by miR-429/ZFP36L2 Axis in Gastric Cancer.

An increasing number of circRNAs have been found to be involved in the development of gastric cancer. However, the function of circ_0003789 in regulating gastric cancer progression is unclear. Here, we aimed to investigate the expression, function and molecular mechanism of circ_0003789 in gastric cancer pathogenesis. Circ_0003789, miR-429 and ZFP36 ring finger protein like 2 (ZFP36L2) mRNA were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was illustrated by 5-Ethynyl-2'-deoxyuridine (Edu), cell counting kit-8 (CCK-8) and colony formation assays. Apoptosis was determined by flow cytometry. Protein level was detected by Western blotting assay. Xenograft assays were used for functional analysis of circ_0003789 in vivo. The relationship between miR-429 and circ_0003789 or ZFP36L2 was predicted by starbase3.0 online database and identified by dual luciferase reporter assay. The expression levels of circ_0003789 and ZFP36L2 were significantly upregulated in gastric cancer tissues and cells, while the expression of miR-429 was downregulated. Downregulation of circ_0003789 inhibited gastric cancer cell growth and invasion and promoted apoptosis in vitro. Circ_0003789 acted as a sponge of miR-429. Moreover, miR-429 silencing by miR-429 inhibitors attenuated the effects of circ_0003789 interference on cell growth, apoptosis and invasion. ZFP36L2 was targeted by miR-429, and the effects of miR-429 on cell growth, invasion and apoptosis were attenuated by ZFP36L2 overexpression. Circ_0003789 could enhance ZFP36L2 expression by interacting with miR-429. Silencing of circ_0003789 inhibited tumor growth in vivo. Circ_0003789 regulates tumor progression in gastric cancer through miR-429/ZFP36L2 axis. This finding implies that circ_0003789 may be a therapeutic target for gastric cancer.

LncRNA LINC02535 Induces Colorectal Adenocarcinoma Progression via Modulating miR-30d-5p/CHD1.

Growing evidence has suggested that lncRNAs play a significant role in the development of colorectal adenocarcinoma. LncRNA LINC02535 was a potential novel lncRNA marker of neoplastic processes of the colon. Nevertheless, the function and mechanisms of LINC02535 in colorectal adenocarcinoma remain unclear. Proteins levels were measured by western blotting. EdU, CCK-8, Transwell, and wound healing assays were performed to investigate the function of LINC02535 in colorectal adenocarcinoma. The distribution of LINC02535 in cells was evaluated by subcellular fractionation assay. The interaction among RNAs was identified by luciferase reporter and RIP assays. In this study, our findings revealed that LINC02535 was highly expressed in colorectal adenocarcinoma cells. Knockdown of LINC02535 inhibited colorectal adenocarcinoma cell proliferation, migration, and invasion. Mechanistically, LINC02535 bound with miR-30d-5p and worked as a competing endogenous RNA to facilitate the expression of messenger RNA chromodomain helicase DNA-binding protein 1 (CHD1). miR-30d-5p directly targeted the sequence of CHD1 3'-untranslated region. Notably, CHD1 upregulation abolished the suppressive influence of LINC02535 inhibition on the malignant phenotypes of colorectal adenocarcinoma cells. Overall, it was disclosed that LINC02535 played an oncogenic role in colorectal adenocarcinoma progression by sponging miR-30d-5p to upregulate CHD1 expression.

Novel H2S-Releasing hydrogel for wound repair via in situ polarization of M2 macrophages.

Hydrogen sulfide (H2S), as a gaseous messenger, exhibits potential therapeutic effects in biological and clinical applications. Herein, an in situ forming biomimetic hyaluronic acid (HA) hydrogel was used as a matrix to dope a pH-controllable H2S donor, JK1, to form a novel HA-JK1 hybrid system. This HA-JK1 hydrogel was designed as an ideal delivery scaffold for JK1 with pH-dependent prolonged H2S releasing profile. In vitro study suggested that JK1 could induce the polarization of M2 phenotype indicating a higher pro-healing efficiency of macrophages. The in vivo studies on dermal wounds showed that the HA-JK1 hybrid hydrogel significantly accelerated the wound regeneration process through enhanced re-epithelialization, collagen deposition, angiogenesis and cell proliferation. Furthermore, the in vivo results also demonstrated a higher level of M2 polarization in HA-JK1 treated group with reduced inflammation and improved wound remodeling effects, which was consistent with the in vitro results. These observations could be considered as a key to the efficient wound treatment. Therefore, we suggest that HA-JK1 can be used as a novel wound dressing material toward cutaneous wound model in vivo. This system should significantly enhance wound regeneration through the release of H2S that induces the expression of M2 macrophage phenotype.

The oncoprotein HBXIP facilitates metastasis of hepatocellular carcinoma cells by activation of MMP15 expression.

Background: Due to the high recurrence and metastasis rate, the clinical outcomes of patients with hepatocellular carcinoma (HCC) are still unsatisfactory. Hepatitis B virus X-interacting protein (HBXIP) has been reported to play crucial roles in carcinogenesis. Purpose: We aimed to reveal the functional significance and underlying mechanism of HBXIP in HCC metastasis. Methods: Cell transwell assay, in vivo metastasis model, real-time PCR, western blot analysis, luciferase reporter and chromatin immunoprecipitation assays were applied. Results: Here, we detected the HBXIP expression level and determined its clinical significance in HCC. We found that HBXIP was significantly upregulated in HCC tissues, and correlated with vascular invasion, tumor metastasis and worse prognosis of HCC patients. HBXIP enhanced cell migration and invasion in vitro, and promoted the metastasis of HCC in vivo. Furthermore, we confirmed that HBXIP increased MMP15 expression through association with proto-oncogene c-myc. Depletion of c-myc abolished HBXIP-mediated MMP-15 upregulation. We also observed a positive correlation between HBXIP and MMP15 expression in HCC tissues. Conclusion: Our results establish a novel function for HBXIP-MMP15 regulation in HCC metastasis and suggest its candidacy as a new prognostic biomarker and therapeutic target for HCC metastasis.

Curcumin ameliorates cisplatin-induced cystopathy via activating NRF2 pathway.

OBJECTIVES: The present work evaluated preventive effect of curcumin on cisplatin-induced bladder cystopathy. METHODS: Fifteen female rats were divided into (i) Control group administered with physiological saline solution for 5 days; (ii) Cis-P group injected with cisplatin (6 mg/kg); and (iii) Cis-Cur group given cisplatin (6 mg/kg) with curcumin for 5 consecutive days. The function of bladder was measured by means of urodynamic analysis. Furthermore, hematoxylin-eosin staining and Masson trichrome staining were performed for morphological analysis. The cell apoptosis was evaluated through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and flow cytometry. The expression of nerve growth factor (NGF), NF-E2-related factor 2, and hemeoxygenase-1 (HO-1) levels were measured through Western blotting. RESULTS: Urodynamic assay and histopathological manifestations revealed that curcumin ameliorated the bladder dysfunction induced by cisplatin. The level of cisplatin-induced apoptosis in the bladder decreased following curcumin treatment. Also, the increased protein expression of NGF indicated that the curcumin could offer neuroprotection for bladder against cisplatin. Curcumin also activated NRF2, and elevated the expression of HO-1, but curcumin could not rescue cisplatin-induced apoptosis in the cell lines with knockdown of NRF2. CONCLUSIONS: Taken together, the results of this paper showed that curcumin could ameliorate cisplatin-induced cystopathy and inhibit the apoptosis of bladder cell in cisplatin-treated rats. This may be attributed to curcumin's broad biological functions, particularly antioxidant effect, and to its ability to activate the NRF2 protein.

Author Correction: Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

ATPase activity regulation by leader peptide processing of ABC transporter maturation and secretion protein, NukT, for lantibiotic nukacin ISK-1.

Lantibiotic nukacin ISK-1 is produced by Staphylococcus warneri ISK-1. The dual functional transporter NukT, an ABC transporter maturation and secretion protein, contributes to cleavage of the leader peptide from the prepeptide (modified NukA) and the final transport of nukacin ISK-1. NukT consists of an N-terminal peptidase domain (PEP), a C-terminal nucleotide-binding domain (NBD), and a transmembrane domain (TMD). In this study, NukT and its peptidase-inactive mutant were expressed, purified, and reconstituted into liposomes for analysis of their peptidase and ATPase activities. The ATPase activity of the NBD region was shown to be required for the peptidase activity of the PEP region. Furthermore, we demonstrated for the first time that leader peptide cleavage by the PEP region significantly enhanced the ATPase activity of the NBD region. Taken together, the presented results offer new insights into the processing mechanism of lantibiotic transporters and the necessity of interdomain cooperation.

Long Noncoding RNA HCAL Facilitates the Growth and Metastasis of Hepatocellular Carcinoma by Acting as a ceRNA of LAPTM4B.

Long noncoding RNAs (lncRNAs) are a new class of regulatory noncoding RNAs. Emerging evidences indicate that lncRNAs play a critical role in the development of hepatocellular carcinoma (HCC). Although several lncRNAs have been annotated, the association of most lncRNAs with HCC is unknown. In this study, we investigated lncRNA alterations in HCC by performing lncRNA microarray analysis. We identified a novel lncRNA called HCC-associated lncRNA (HCAL) that was highly expressed in HCC tissues. HCAL upregulation was clinically associated with poor differentiation, intravascular cancer embolus, and decreased survival of patients with HCC. HCAL silencing significantly inhibited the growth and metastasis of HCC cells both in vitro and in vivo. Interestingly, transcriptome-sequencing analysis of HCAL-knockdown cells showed alterations in some cancer-related pathways. Mechanistically, HCAL directly interacted with and functioned as a sponge for microRNAs such as miR-15a, miR-196a, and miR-196b to modulate LAPTM4B expression. Taken together, our findings suggest the presence of a novel lncRNA-miRNA-mRNA regulatory network, i.e., the HCAL-miR-15a/miR-196a/miR-196b-LAPTM4B network, in HCC and indicate that HCAL may be a potential target for treating HCC.

Down-regulated GATA-1 up-regulates interferon regulatory factor 3 in lung adenocarcinoma.

Interferon regulatory factor 3 (IRF-3) is widely known for its prompt response against viral infection by activating the interferon system. We previously reported that E2F1, Sp1 and Sp3 regulated transcriptional activity of IRF-3. Recently, different expression patterns of IRF-3 were found in lung cancer, leading to the alternation of the immunomodulatory function in tumorigenesis. However, the mechanism of transcriptional regulation of IRF-3 in lung cancer has not been extensively studied. Here, we investigated the characterization of IRF-3 promoter and found that GATA-1 bound to a specific domain of IRF-3 promoter in vitro and in vivo. We found elevated IRF-3 and decreased GATA-1 gene expression in lung adenocarcinoma in Oncomine database. Additionally, higher IRF-3 gene expression was observed in human lung adenocarcinoma, accompanied by aberrant GATA-1 protein expression. We further analyzed the relationship of GATA-1 and IRF-3 expression in lung adenocarcinoma cell lines and found that inhibition of GATA-1 by siRNA increased the promoter activity, mRNA and protein levels of IRF-3, while over-expression of GATA-1 down-regulated IRF-3 gene expression. Taken together, we conclude that reduced GATA-1 could be responsible for the upregulation of IRF-3 in lung adenocarcinoma cells through binding with a specific domain of IRF-3 promoter.

High expression of Rap2A is associated with poor prognosis of patients with hepatocellular carcinoma.

Rap2A is overexpressed in a multitude of human cancers and plays an important role in cytoskeleton rearrangement, arteriogenesis and cell migration. However, its role and function in hepatocellular carcinoma (HCC) has not yet been explored. Here, we aimed to investigate the expression of Rap2A in HCC and the relationship between Rap2A and clinicopathologic features of patients. Western blot and quantitative real-time PCR (qRT-PCR) showed that Rap2A was remarkably upregulated in HCC tissues compared to adjacent normal liver tissues. Immunohistochemistry (IHC) showed that Rap2A was mainly localized in the cytoplasm rather than nuclei in HCC tissues. Overexpression of Rap2A was significantly correlated with tumor size (P=0.019), metastasis (P=0.002), pathological differentiation (P=0.028) and vascular invasion (P=0.017) in HCC. Kaplan-Meier analysis demonstrated that HCC patients with high Rap2A expression had shorter overall survival time than those with low Rap2A expression (P=0.011). Furthermore, High level of Rap2A was a risk factor for HCC patients according to Cox's proportional hazard regression (P=0.026). In summary, our results suggest that high expression of Rap2A is involved in HCC progression and might be a novel prognostic indicator for patients.

Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of α-Tubulin and Inhibition of Microtubule Formation.

Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 µM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5' adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.

Growth hormone used to control intractable bleeding caused by radiation-induced gastritis.

Intractable bleeding caused by radiation-induced gastritis is rare. We describe a 69-year-old man with intractable hemorrhagic gastritis induced by postoperative radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory therapy with or without octreotide was initiated for hemostasis over three months, melena still occurred off and on, and the patient required blood transfusions to maintain stable hemoglobin. Finally growth hormone was used in the treatment of hemorrhage for two weeks, and hemostasis was successfully achieved. This is the first report that growth hormone has been used to control intractable bleeding caused by radiation-induced gastritis.