Diverticular peroral endoscopic myotomy (D-POEM) for symptomatic oesophageal diverticulum: a multicentre cohort study with a minimum follow-up of 3 years.

OBJECTIVE: To evaluate the medium- and long-term outcomes of diverticular peroral endoscopic myotomy (D-POEM) for symptomatic oesophageal diverticulum. METHODS: Consecutive patients with symptomatic oesophageal diverticulum who underwent D-POEM from 1st May 2016 to 1st April 2020 in 6 centres were extracted and researched. Symptoms assessed by the modified Eckardt score were registered pre- and post-D-POEM at 1, 6, 12, 24 and 36 months. RESULTS: A total of 34 patients with Zenker's diverticulum (ZD, n = 12), mid-oesophageal diverticulum (MED, n = 12), and epiphrenic diverticulum (ED, n = 10) were included. Complete septotomy was achieved in a mean of 39.15 min, with 100% technical success. No severe intraoperative or postoperative complications were observed. Five patients exhibited subcutaneous emphysema, while 1 had mucosal injury. The mean Eckardt score was 8.59 preoperatively and 2.56 at 1 month, 2.09 at 6 months, 2.21 at 12 months, 2.15 at 24 months, and 2.21 at 36 months postoperatively. The total clinical success rates at 1, 6, 12, 24 and 36 months postoperatively were 97.1%, 97.1%, 94.1%, 91.2%, and 88.2%, respectively. With a median follow-up of 47.2 months, four patients suffered symptom relapse, with a total clinical success rate of 88.2%. A long disease duration, a high Eckardt score, and coexistence of achalasia were identified as risk factors for symptomatic recurrence by multivariable Cox analysis. CONCLUSIONS: D-POEM is an effective and durable treatment for patients with symptomatic oesophageal diverticulum.

LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability.

BACKGROUND: Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling. RESULTS: One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells. CONCLUSIONS: The newly identified SNHG16-EIF4A3-RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.

Unravelling the Structure of a Medium-Sized Metalloid Gold Nanocluster and its Filming Property.

Unravelling the structure of thiolated metalloid gold nanoclusters in the medium-sized range by single crystal X-ray crystallography (SCXC) is challenging. Herein, we successfully synthesized a novel Au67 (SR)35 nanocluster, and unravelled its single crystal structure by SCXC, which features a mix-structured Au48 kernel protected by one Au4 (SR)5 staple and fifteen Au(SR)2 staples. Unprecedentedly, this structure can be thermally induced to aggregate into larger nanoparticles and self-deposit to form a gold nanoparticles film onto the walls of a vial or other substrates such as quartz, mica or ceramic, which can be developed into a facile, substrate-universal and scalable filming method. The film exhibits high sensitivity, uniformity and recyclability as a surface-enhanced Raman scattering (SERS) substrate and can be applied for detecting multiple organic pollutants.

Synthesizing Photoluminescent Au28 (SCH2 Ph-t Bu)22 Nanoclusters with Structural Features by Using a Combined Method.

We present a method for atomically precise nanocluster synthesis. As an illustration, we introduced the reducing-ligand induction combined method and synthesized a novel nanocluster, which was determined to be Au28 (SCH2 Ph-t Bu)22 with the same number of gold atoms as existing Au28 (SR)20 nanoclusters but different ligands (hetero-composition-homo-size). Compared with the latter, the former has distinct properties and structures. In particular, a novel kernel evolution pattern is reported, i.e., the quasi-linear growth of Au4 -tetrahedron by sharing one vertex and structural features, including a tritetrahedron kernel with two bridging thiolates and two Au6 (SCH2 Ph-t Bu)6 hexamer chair-like rings on the kernel surface were also first reported, which endow Au28 (SCH2 Ph-t Bu)22 with the best photoluminescence quantum yield among hydrophobic thiolated gold nanoclusters so far, probably due to the enhanced charge transfer from the bi-ring to the kernel via Au-Au bonds.

Compression-Driven Internanocluster Reaction for Synthesis of Unconventional Gold Nanoclusters.

Can the active kernels in ultrasmall metal nanoparticles (nanoclusters, NCs) react with one another, or can the internanocluster reaction occur when they are in close enough proximity? To resolve this fundamental issue, we investigated the solid-state internanocluster reaction of the most studied gold NC Au25 (SR)18 (SR: thiolate). A novel NC was produced by increasing the pressure to 5 GPa, whose composition was determined to be Au32 (SC2 H4 Ph)24 by mass spectrometry and thermogravimetric analysis. As revealed by single-crystal X-ray crystallography, the structure, a bicuboid Au14 kernel and three pairs of interlocked trimetric staples, has not been reported and endows the NC with obvious photoluminescence. DFT calculations indicate that the staples contribute substantially to the absorption properties. Further experiments reveal the pressure (internanocluster distance) can tune the internanocluster reaction, and the resulting product is not necessarily the thermodynamic product.

Polymorphisms of TGFBR1, TLR4 are associated with prognosis of gastric cancer in a Chinese population.

BACKGROUND: Helicobacter pylori (H. pylori)-induced gastric cancer is an intricate progression of immune response against H. pylori infection. IL-16, TGF-ß1 and TLR4 pathways were the mediators involved in the immune response. We hypothesized that genetic variations in genes of these pathways have potential susceptibility to gastric cancer risk, and predict clinical outcomes of patients. METHODS: To investigate the susceptibility and prognostic value of genetic variations of IL-16, TGFBR1 and TLR4 pathways to gastric cancer, we performed a case-control study combined a retrospective study in a Chinese population. Genotyping for all polymorphisms was based on the Sequenom's MassARRAY platform, and H. pylori infection was determined by using an immunogold testing kit. RESULTS: We found rs10512263 CC genotype was found to be a decreased risk of gastric cancer (CC vs. TT: adjusted OR = 0.54, 95% CI 0.31-0.97); however, rs334348 GG genotype was associated with increased risk of gastric cancer (GG vs. AA: adjusted OR = 1.51, 95% CI 1.05-2.18). We found that carriers harboring rs1927911 A allele (GA/AA) or rs10512263 C allele (CT/CC) have unfavorable survival time than none carriers (rs1927911: GA/AA vs. GG: adjusted HR = 1.27, 95% CI 1.00-1.63; rs10512263: CT/CC vs. TT: adjusted HR = 1.29, 95% CI 1.02-1.63) and that individuals harboring both two minor alleles (rs1927911 GA/AA and rs10512263 CT/CC) suffered a significant unfavorable survival (adjusted HR = 1.64, 95% CI 1.17-2.31). CONCLUSION: In short, we concluded that two polymorphisms (rs334348, rs10512263) in TGFBR1 were associated with risk of gastric cancer, and that TLR4 rs1927911 and TGFBR1 rs10512263 were associated with clinical outcomes of gastric cancer patients.

Advanced Strategies for Eliminating the cccDNA of HBV.

Persistent hepatitis B virus (HBV) infection of hepatocytes is associated with a covalently closed circular DNA (cccDNA) episome. Although serologic hepatitis B surface antigen tests are negative, the presence of cccDNA is obviously increased in HBeAg-positive patients compared with that in HBeAg-negative patients, inactive carriers and patients. Moreover, trace cccDNA levels can also be found in the liver cells of patients with resolved hepatitis B infections. Therefore, clearance of cccDNA in hepatocytes could be an effective cure for HBV. In this review, we summarize the strategies that have been employed to eliminate cccDNA in recent years and discuss the future development of treatments for chronic hepatitis B.

Peroral endoscopic myotomy treatment for symptomatic esophageal diverticulum: a systematic review and meta-analysis.

Peroral endoscopic myotomy (POEM) is a rapidly evolving technique for the treatment of esophageal diverticulum. The aim of this study was to perform a systematic review and meta-analysis of the literature focusing on POEM for symptomatic esophageal diverticula, including an in-depth evaluation of its efficacy, safety, and limitations. A comprehensive literature search was completed to identify articles that examined the efficacy and safety of POEM for esophageal diverticula. Heterogeneity among studies was assessed using the I2 statistic. Meta-regression and sensitivity analyses were performed to explore the sources of heterogeneity and assess potentially important covariates influencing the main outcomes. Primary endpoints such as rates of success, adverse events, and recurrences were evaluated. P values of ≤0.05 were considered statistically significant. Nine studies with a total of 153 patients were enrolled. Pooled technical success, clinical success, adverse events, and recurrence rates were 99% [95% confidence interval (CI), 97-100%; I2 = 0%), 94% (95% CI, 89-97%; I2 = 24%), 2% (95% CI, 0-6%, I2 = 0%), and 0% (95% CI, 0-1%; I2 = 0%), respectively. The pooled perforation rate was 6% (95% CI, 1-11%; I2 = 0%). Meta-regression analysis indicated that esophageal diverticula types and motility disorders were not associated with the clinical success rate (P > 0.05). POEM is a feasible, safe, and effective treatment for symptomatic esophageal diverticula, with low adverse events and recurrence rates.

Distance makes a difference in crystalline photoluminescence.

Crystallization-induced photoluminescence weakening was recently revealed in ultrasmall metal nanoparticles. However, the fundamentals of the phenomenon are not understood yet. By obtaining conformational isomer crystals of gold nanoclusters, we investigate crystallization-induced photoluminescence weakening and reveal that the shortening of interparticle distance decreases photoluminescence, which is further supported by high-pressure photoluminescence experiments. To interpret this, we propose a distance-dependent non-radiative transfer model of excitation electrons and support it with additional theoretical and experimental results. This model can also explain both aggregation-induced quenching and aggregation-induced emission phenomena. This work improves our understanding of aggregated-state photoluminescence, contributes to the concept of conformational isomerism in nanoclusters, and demonstrates the utility of high pressure studies in nanochemistry.

MicroRNA-139 inhibits the proliferation, migration and invasion of gastric cancer cells by directly targeting ρ-associated protein kinase 1.

The expression, function and underlying mechanisms of microRNA-139 (miR-139) in gastric cancer were investigated in the present study. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-139 expression in gastric cancer tissues and cell lines. The effects of miR-139 overexpression on gastric cancer cell proliferation, migration and invasion were evaluated. ρ-associated protein kinase 1 (ROCK1) was predicted as a downstream target of miR-139 and its role in gastric cancer was assessed by bioinformatics analysis, luciferase reporter assay, RT-qPCR and western blot analysis. ROCK1 overexpression was established to investigate if the effects of miR-139 on gastric cancer cells may be attenuated. The results indicated that miR-139 was aberrantly downregulated in gastric cancer tissues and cell lines. Increased miR-139 expression reduced gastric cancer cell proliferation, migration and invasion. ROCK1 was demonstrated to be a direct target of miR-139 in gastric cancer and ROCK1 overexpression reversed the suppressive effects on gastric cancer cell proliferation, migration and invasion induced by miR-139 overexpression. The present study provides clear evidence demonstrating the anti-oncogenic activity of miR-139 in human gastric cancer, as mediated by the targeted downregulation of ROCK1.

MicroRNA-363-3p is downregulated in hepatocellular carcinoma and inhibits tumorigenesis by directly targeting specificity protein 1.

microRNAs exhibit important regulatory roles in tumorigenesis and tumor development, such as in hepatocellular carcinoma (HCC). The present study aimed to investigate the expression and functional roles of microRNA (miR)­363­3p in HCC. miR-363-3p expression levels in a number of HCC tissues and cell lines were measured by reverse transcription-quantitative PCR (RT­qPCR). The effects of miR­363­3p expression on HCC cell proliferation, migration and invasion were exa-mined by MTT assay, Transwell migration and invasion assay, respectively. The effects of miR­363­3p on its downstream target gene, specificity protein 1 (SP1), were examined by bioinformatics analysis, luciferase reporter assay, RT­qPCR and western blotting. An SP1 overexpression vector was subsequently transfected into HCC cells to assess any selective effects on miR­363­3p in modulating HCC. The results revealed that miR­363­3p expression levels were downregulated in both HCC tissues and cell lines, and this low expression level was correlated with tumor size, tumor­node­metastasis stage and venous infiltration in patients with HCC. Upregulation of miR­363­3p inhibited cell proliferation, migration and invasion in HCC cell cultures. In HCC cells transfected with an SP1 expression vector the miR­363­3p­induced tumor suppressive roles on cell proliferation, migration and invasion were reversed. In conclusion, results from the present study indicated that miR­363­3p is a tumor suppressor in HCC and functions through a mechanism involving SP1, suggesting that miR­363­3p may be a potential new therapeutic target for the treatment of HCC.