Modified Unit-Mediated Strand Displacement Reactions for Direct Detection of Single Nucleotide Variants in Active Double-Stranded DNA.

Accurate identification of single nucleotide variants (SNVs) in key driver genes holds a significant value for disease diagnosis and treatment. Fluorescent probes exhibit tremendous potential in specific, high-resolution, and rapid detection of SNVs. However, additional steps are required in most post-PCR assays to convert double-stranded DNA (dsDNA) products into single-stranded DNA (ssDNA), enabling them to possess hybridization activity to trigger subsequent reactions. This process not only prolongs the complexity of the experiment but also introduces the risk of losing target information. In this study, we proposed two strategies for enriching active double-stranded DNA, involving PCR based on obstructive groups and cleavable units. Building upon this, we explored the impact of modified units on the strand displacement reaction (SDR) and assessed their discriminatory efficacy for mutations. The results showed that detection of low variant allele frequencies (VAF) as low as 0.1% can be achieved. The proposed strategy allowed orthogonal identification of 45 clinical colorectal cancer tissue samples with 100% specificity, and the results were generally consistent with sequencing results. Compared to existing methods for enriching active targets, our approach offers a more diverse set of enrichment strategies, characterized by the advantage of being simple and fast and preserving original information to the maximum extent. The objective of this study is to offer an effective solution for the swift and facile acquisition of active double-stranded DNA. We anticipate that our work will facilitate the practical applications of SDR based on dsDNA.

Mediating role of body mass index on the relationship between physical activity and physical fitness among junior high school students in Shanghai.

Objectives: This study explored the relationship between physical activity (PA), body mass index (BMI), and physical fitness among junior high school students in Shanghai. Methods: A nationwide offline survey was conducted in Shanghai between August and December 2023, using a purposive sampling design. A total of 403 questionnaires were administered to 10 ninth-grade classes in 10 schools in Shanghai and 372 responses were included in the final analysis. Smart-PLS 4.0, structural equation modeling techniques were employed to analyze the collected data. Results: Light physical activity (LPA) had no influence on BMI, 800/1000 m (800/1000 M), sitting forward bend (FB), standing long jump (SLJ), 50 m (50 M), or vital capacity (VC). The results of part hypothesis supported the hypothetical model and explained that BMI had a negatively influence on 50 M, 800/1000 M and SLJ, BMI had a positively influence on VC. Moderate physical activity (MPA) had a negatively influence on BMI, but vigorous physical activity (VPA) had a positively influence on BMI, they both had influence on 50 M and FB, but had no influence on 800/1000 M, SLJ, and VC. Conclusions: BMI, MPA and VPA were found as pivotal factors influencing physical fitness, MPA and VPA were found to have divergent effects on BMI. This study highlighted the multifaceted nature of the relationship between PA, BMI, and physical fitness in junior high school students in Shanghai.

A novel entropy-driven dual-output mode integrated with DNAzyme for enhanced microRNA detection.

Accurate microRNA (miRNA) detection is pivotal in the diagnosis and monitoring of cancer. Entropy-driven catalysis (EDC) has attracted widespread attention as an enzyme-free, isothermal technique for miRNA detection owing to its inherent simplicity and reliability. However, conventional EDC is a single-output mode, limiting the efficiency of signal amplification. In this study, a novel EDC dual-output mode was employed in conjunction with DNAzyme, resulting in the development of an EDC dual-end DNAzyme (EDC-DED) approach for highly sensitive miRNA detection. In this system, miRNA-21 initiated the EDC reaction, producing a large amount of catalytically active dual-end Mg2+-dependent DNAzyme. The DNAzyme further cleaved the reporter cyclically, generating a notably amplified fluorescence signal. The proposed method achieved a low detection limit of 2 pM. Compared with the traditional EDC single-end DNAzyme (EDC-SED) strategy, the present method exhibited superior amplification efficiency, enhancing detection sensitivity by approximately 46.5-fold. Furthermore, this platform demonstrated ideal specificity, satisfactory reproducibility and acceptable detection capabilities in clinical serum samples. Therefore, the straightforward and convenient strategy is a potential tool for miRNA analysis, which may provide a new perspective for biological analysis and clinical application.

DNA-based molecular classifiers for the profiling of gene expression signatures.

Although gene expression signatures offer tremendous potential in diseases diagnostic and prognostic, but massive gene expression signatures caused challenges for experimental detection and computational analysis in clinical setting. Here, we introduce a universal DNA-based molecular classifier for profiling gene expression signatures and generating immediate diagnostic outcomes. The molecular classifier begins with feature transformation, a modular and programmable strategy was used to capture relative relationships of low-concentration RNAs and convert them to general coding inputs. Then, competitive inhibition of the DNA catalytic reaction enables strict weight assignment for different inputs according to their importance, followed by summation, annihilation and reporting to accurately implement the mathematical model of the classifier. We validated the entire workflow by utilizing miRNA expression levels for the diagnosis of hepatocellular carcinoma (HCC) in clinical samples with an accuracy 85.7%. The results demonstrate the molecular classifier provides a universal solution to explore the correlation between gene expression patterns and disease diagnostics, monitoring, and prognosis, and supports personalized healthcare in primary care.

Nucleic acid-based small molecules as targeted transcription therapeutics for immunoregulation.

Transcription therapy is an emerging approach that centers on identifying the factors associated with the malfunctioning gene transcription machinery that causes diseases and controlling them with designer agents. Until now, the primary research focus in therapeutic gene modulation has been on small-molecule drugs that target epigenetic enzymes and critical signaling pathways. However, nucleic acid-based small molecules have gained popularity in recent years for their amenability to be pre-designed and realize operative control over the dynamic transcription machinery that governs how the immune system responds to diseases. Pyrrole-imidazole polyamides (PIPs) are well-established DNA-based small-molecule gene regulators that overcome the limitations of their conventional counterparts owing to their sequence-targeted specificity, versatile regulatory efficiency, and biocompatibility. Here, we emphasize the rational design of PIPs, their functional mechanisms, and their potential as targeted transcription therapeutics for disease treatment by regulating the immune response. Furthermore, we also discuss the challenges and foresight of this approach in personalized immunotherapy in precision medicine.

A Spatially Controlled Proximity Split Tweezer Switch for Enhanced DNA Circuit Construction and Multifunctional Transduction.

DNA strand displacement reactions are vital for constructing intricate nucleic acid circuits, owing to their programmability and predictability. However, the scarcity of effective methods for eliminating circuit leakages has hampered the construction of circuits with increased complexity. Herein, a versatile strategy is developed that relies on a spatially controlled proximity split tweezer (PST) switch to transduce the biomolecular signals into the independent oligonucleotides. Leveraging the double-stranded rigidity of the tweezer works synergistically with the hindering effect of the hairpin lock, effectively minimizing circuit leakage compared with sequence-level methods. In addition, the freely designed output strand is independent of the target binding sequence, allowing the PST switch conformation to be modulated by nucleic acids, small molecules, and proteins, exhibiting remarkable adaptability to a wide range of targets. Using this platform, established logical operations between different types of targets for multifunctional transduction are successfully established. Most importantly, the platform can be directly coupled with DNA catalytic circuits to further enhance transduction performance. The uniqueness of this platform lies in its design straightforwardness, flexibility, scalable intricacy, and system compatibility. These attributes pave a broad path toward nucleic acid-based development of sophisticated transduction networks, making them widely applied in basic science research and biomedical applications.

Avoided Level Crossing and Entangled States of Interacting Hydrogen Molecules Detected by the Quantum Superposition Microscope.

Pump-probe measurements by ultrashort THz pulses can be used to excite and follow the coherence dynamics in the time domain of single hydrogen molecules (H2) in the junction of a scanning tunneling microscope (STM). By tailoring the resonance frequency through the sample bias, we identified two spectral signatures of the interactions among multiple H2 molecules. First, the avoided level crossing featured by energy gaps ranging from 20 to 80 GHz was observed because of the level repulsion between two H2 molecules. Second, the tip can sense the signal of H2 outside the junction through the projective measurement on the H2 inside the junction, owing to the entangled states created through the interactions. A dipolar-type interaction was integrated into the tunneling two-level system model of H2, enabling accurate reproduction of the observed behaviors. Our results obtained by the quantum superposition microscope reveal the intricate quantum mechanical interplay among H2 molecules and additionally provide a 2D platform to investigate unresolved questions of amorphous materials.

DNA Methylation Modification Patterns Identify Distinct Prognosis and Responses to Immunotherapy and Targeted Therapy in Renal Cell Carcinoma.

BACKGROUND: Considering the remarkable heterogeneity of biological features of renal cell carcinoma (RCC), the current clinical classification that only relies on classic clinicopathological features is in urgent need of improvement. Herein, we aimed to conduct DNA methylation modification patterns in RCC. METHODS: We retrospectively curated multiple RCC cohorts, comprising TCGA-KIRC, TCGA-KICH, TCGA-KIRP, and E-MTAB-1980. DNA methylation modification patterns were proposed with an unsupervised clustering algorithm based on 20 DNA methylation regulators. Immunological features were characterized using tumor-infiltrating immune cells and immunomodulators. Sensitivity to immuno- or targeted therapy was estimated with submap and Genomics of Drug Sensitivity in Cancer (GDSC). DNA methylation score (DMS) was developed with principal component analysis. RESULTS: Three DNA methylation modification patterns were conducted across RCC patients, namely C1, C2 and C3. Among them, C3 displayed the most remarkable survival advantage. The three patterns presented in agreement with immune phenotypes: immune-desert, immune-excluded, and immune-inflamed, respectively. These patterns displayed distinct responses to anti-PD-1 and targeted drugs. DMS enabled the quantification of DNA methylation status individually as an alternative tool for prognostic estimation. CONCLUSIONS: The DNA methylation molecular patterns we proposed are an innovative complement to the traditional classification of RCC, which might contribute to precision medicine.

Progress in central retinal artery occlusion: a narrative review.

Central retinal artery occlusion (CRAO) is a catastrophic ophthalmic emergency that severely impairs a patient's visual function, often reducing visual acuity to counting fingers or worse. Progress in CRAO research has provided new information regarding its epidemiological characteristics and led to useful assessments through various ophthalmic examinations. Additional insights about CRAO have been gained through studies of its pathophysiological mechanisms, improving intervention timing and enhancing patient prognosis. Treatment for CRAO has evolved, particularly with assistance from surgical instruments and surgical robots. Although surgical treatment is now possible, this option is not widely recognized by ophthalmologists. Conservative therapies have limited benefits compared with the natural course of disease. Recently, pars plana vitrectomy plus endovascular surgery has received considerable interest among ophthalmologists because of its potential efficacy in the treatment of CRAO. Considering the inconsistencies in rationale and efficacy of CRAO treatment modalities, it is important to distinguish between treatment effects and the natural courses of various CRAO subclasses. This narrative review explores progress in CRAO epidemiology, pathophysiology, ophthalmic examination, and treatment.

Two Cases of Laparoscopic Resection of Siewert Type II Adenocarcinoma of the Esophagogastric Junction Using a Transhiatal Approach and Complicated by Hemopericardium.

BACKGROUND Siewert type II adenocarcinoma of the esophagogastric junction is located at the boundary of the distal esophagus and gastric cardia, and surgical resection is currently performed using open or laparoscopic methods. This report presents 2 cases of laparoscopic resection of Siewert type II adenocarcinoma of the esophagogastric junction using a transhiatal approach, complicated by hemopericardium. CASE REPORT We present 2 patients diagnosed with Siewert type II esophagogastric junction cancer. A 67-year-old man had intermittent dull pain in the epigastrium without apparent cause for 10 months. A 69-year-old man had persistent dull pain in the middle and upper abdomen for more than 3 months and acid reflux after eating. Gastroscopy with pathological examination confirmed the diagnoses. The patients underwent laparoscopic transhiatal total gastrectomy according to the Japanese Gastric Cancer Treatment Guidelines 2018 (5th edition). Pathological analysis classified the cancers as T3N1M0 and T2N0M0, respectively. The patients' cases were complicated with hemopericardium 18 h and 23 h after surgery, respectively. The shared clinical symptoms of the patients included tachycardia and low blood pressure. Cardiovascular color Doppler ultrasound and computed tomography (CT) were used to identify the hemopericardium. Following emergent ultrasound-guided pericardiocentesis and drainage, the vital signs of the patients improved. Both patients recovered well, and no other complications occurred. CONCLUSIONS Hemopericardium is a life-threatening complication for patients with esophageal-gastric junction cancer who undergo transhiatal laparoscopic surgery. Quick detection and intervention for postoperative hemopericardium following laparoscopic transhiatal total gastrectomy are important. Ultrasound-guided pericardiocentesis and drainage is effective for the treatment of postoperative hemopericardium.

Genomic Insights into Adaptation to Karst Limestone and Incipient Speciation in East Asian Platycarya spp. (Juglandaceae).

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes, and its only congeneric species, P. strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics, and the driving forces underneath the incipient speciation of the two Platycarya lineages.

Temperature-boosted PAM-less activation of CRISPR-Cas12a combined with selective inhibitors enhances detection of SNVs with VAFs below 0.01.

The precise identification of rare single nucleotide variations (SNVs) concomitant with excess wild-type DNA is a valuable method for minimally invasive disease diagnosis and early prediction of drug responsiveness. Selective enrichment of mutant variants via strand displacement reaction offers an ideal approach of SNVs analysis but fails to differentiate wildtype from mutants with variant allele fraction (VAF) < 0.01%. Here, we demonstrate that integration of PAM-less CRISPR-Cas12a and adjacent mutation-enhanced inhibition of wild-type alleles enables highly sensitive measurement of SNVs well below the 0.01% VAF threshold. Raising the reaction temperature to the upper limit of LbaCas12a helps to boost PAM-less activation of collateral DNase activity, which can be further enhanced using PCR additives, leading to ideal discriminative performance for single point mutations. Along with selective inhibitors bearing additional adjacent mutation, it allowed detection of model EGFR L858R mutants down to 0.001% with high sensitivity and specificity. Preliminary investigation on adulterated genomic samples prepared in two different ways also suggests that it can accurately measure ultralow-abundance SNVs extracted directly from clinical samples. We believe that our design, which combines the superior SNV enrichment capability of strand displacement reaction and unparalleled programmability of CRISPR-Cas12a, has the potential to significantly advance current SNV profiling technologies.

Comparison of infliximab with adalimumab for the treatment of non-infectious uveitis: a systematic review and meta-analysis.

PURPOSE: To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU). METHODS: We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, Grey Matters, Grey Literature Report, OpenGrey, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete remission of inflammation, response to therapy, adverse events and corticosteroid-sparing effect were evaluated. RESULTS: Eleven clinical trials covering 1459 NIU patients were included. Complete remission of inflammation after therapy was achieved in 161 (37.5%) patients in the infliximab group and 151 (39.6%) patients in the adalimumab group. These two groups were not significantly different (P = 0.37). Four studies reported response to anti-TNF therapy involving 449 patients, of whom 241/272 (88.6%) treated with infliximab and 153/177 (86.4%) treated with adalimumab achieved partial or complete remission of inflammation. No significant difference was observed between the two cohorts in terms of response to therapy (P = 0.86). There was no significant difference between infliximab and adalimumab with regard to corticosteroid-sparing effect (P = 0.58). The pooled effect size (P = 0.001) showed a statistically significant difference, with the incidence of adverse events being 17.91% for infliximab and 12.12% for adalimumab. CONCLUSION: Our systematic review and meta-analysis of 11 studies suggests that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with NIU. However, adalimumab has a marginal advantage over infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents in patients with NIU.

Robotic versus laparoscopic surgery for hiatal hernia repair: a systematic literature review and meta-analysis.

The number of robotic hiatal hernia repairs (RHHR) is increasing. However, the superiority of this minimally invasive approach remains controversial. The aim of this study was to evaluate the available literature reporting on outcomes of RHHR compared with laparoscopic hiatal hernia repair (LHHR) in adult patients. The design of this systematic review was developed using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Web of Science, PubMed, the Cochrane Library, and ClinicalTrials.gov databases were searched. Identified publications were reviewed independently by two authors. High heterogeneity was further explored through sensitivity analysis. The primary endpoint was the development of postoperative complications. Secondary endpoints included operation time, intraoperative complications, 30 day readmission rates and length of stay. The analysis was performed using Stata 17.0 software. A total of 7 studies totaling 10078 patients met the inclusion criteria. Five studies included postoperative complications. The postoperative complications rate was 4.25% (302/7111) in the LHHR group, and 3.49% (38/1088) in the RHHR group. Postoperative complications significantly decreased after RHHR compared with LHHR (OR 0.52; 95% CI 0.36 to 0.75, P = 0.000). Three studies involving 2176 patients reported length of hospital stay. In the three studies, the mean Length of hospital stay was 3.2 days in the RHHR group, and 4.2 days in the LHHR group. Length of hospital stay was decreased by a mean of 0.68 days for RHHR compared with LHHR (WMD, - 0.68 days; 95% CI - 1.32 to - 0.03, P = 0.02). There was no significant difference between the RHHR group and the LHHR group regarding operative time, intraoperative complications, and 30 day readmission (P > 0.05). Our research shows that RHHR may be the better option, as the approach decreases postoperative complications and length of hospital stay.

A Novel Intraoperative Leak Test Procedure (GAM Procedure) to Prevent Postoperative Anastomotic Leakage in Gastric Cancer Patients Who Underwent Gastrectomy.

BACKGROUND: Anastomotic leakage following a radical gastrectomy is a serious complication of gastric cancer and esophagogastric junction cancer. The benefit of intraoperative leak testing for the prevention of postoperative anastomotic leakage has been controversial. We introduce a new procedure, which combines the techniques of gastroscopy, air, and methylene blue (GAM) for intraoperative leakage testing. Our objective was to evaluate the efficacy and safety of the GAM procedure for intraoperative leak testing and to compare the surgical complications of gastric cancer patients who underwent gastrectomy with and without intraoperative leak testing using the GAM procedure. MATERIALS AND METHODS: A total of 210 patients who underwent radical gastrectomy for gastric cancer were included. Patients were divided into 2 groups: the intraoperative leak testing group using the GAM procedure (IOLT), and the group for which no intraoperative leak testing was done (NIOLT). Clinical and pathologic characteristics, the incidence of postoperative anastomotic leakage, and other surgical complications were compared between the 2 groups. RESULTS: There were 82 patients in the IOLT group and 82 patients in the NIOLT group after propensity score matching. In the IOLT group, 4 (4.9%) patients were found to have anastomotic discontinuity during the operation; we repaired these anastomotic discontinuities intraoperatively. The incidence of postoperative anastomotic leakage was higher in the NIOLT group compared with the IOLT group, 6 (7.3%) versus 0 (0%), respectively ( P =0.01). The average time of the GAM procedure was 4.99±1.75 minutes. The surgical time was prolonged by 30 minutes in the IOLT group compared with the NIOLT group, 302.2±79.9 versus 272.1±85.2, respectively ( P =0.02). The length of hospital stay, 15.80±4.55 versus 17.00±6.20 ( P =0.16) was reduced in the IOLT group compared with the NIOLT group. The logistic regression model suggested that IOLT, sex, age, Eastern Cooperative Oncology Group, cT stage, tumor diameter, pT stage, pN stage, and Lauren classification were not risk factors for postoperative complication. CONCLUSIONS: The GAM procedure of intraoperative leakage testing can effectively reduce the incidence of postoperative anastomotic leakage in gastric cancer patients undergoing gastrectomy.

Genomic Insights into Adaptation to Karst Limestone and Incipient Speciation in East Asian Platycarya spp. (Juglandaceae).

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes and its only congeneric species, Platycarya strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole-genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics and the driving forces underneath the incipient speciation of the two Platycarya lineages.

[Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance].

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and ß-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. ß-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.

A hairpin probe-mediated exponential amplification reaction for highly sensitive and specific detection of microRNAs.

In this work, we propose a hairpin probe-mediated exponential amplification reaction (HEAR) strategy that combines DNA strand displacement with a "who triggers, who gets generated" mode, providing excellent single-base discrimination and a reduced background signal. The detection limit is 19 aM, which is reduced by 3 orders of magnitude compared to traditional exponential amplification approaches. This one-pot strategy also exhibits a wide dynamic range, high specificity and short detection time. It is expected to become a powerful tool for clinical diagnosis.

Electrical Manipulation of Quantum Coherence in a Two-Level Molecular System.

We report the manipulation of ultrafast quantum coherence of a two-level single hydrogen molecular system by employing static electric field from the sample bias in a femtosecond terahertz scanning tunneling microscope. A H_{2} molecule adsorbed on the polar Cu_{2}N surface develops an electric dipole and exhibits a giant Stark effect. An avoided crossing of the quantum state energy levels is derived from the resonant frequency of the single H_{2} two levels in a double-well potential. The dephasing time of the initial wave packet can also be changed by applying the electric field. The electrical manipulation for different tunneling gaps in three dimensions allows quantification of the surface electrostatic fields at the atomic scale. Our work demonstrated the potential application of molecules as controllable two-level molecular systems.

Efficacy and safety of anastomotic leak testing in gastric cancer: a randomized controlled trial.

BACKGROUND: Anastomosis-related complications such as bleeding, leakage, and strictures, continue to be serious complications of gastric cancer surgery. Presently, these complications have yet to be reliably prevented. Here we design a comprehensive leak testing procedure which combines gastroscopy, air, and methylene blue (GAM) leak testing. We aimed to evaluated the efficacy and safety of the GAM procedure in patients with gastric cancer. METHODS: Patients aged 18-85 years without an unresectable factor as confirmed via CT were enrolled in a prospective randomized clinical trial at a tertiary referral teaching hospital and were randomly assigned to two groups: intraoperative leak testing group (IOLT) and no intraoperative leak testing group (NIOLT). The primary endpoint was the incidence of postoperative anastomosis-related complications in the two groups. RESULTS: 148 patients were initially randomly assigned to the IOLT group (n = 74) and to the NIOLT group (n = 74) between September 2018 and September 2022. After exclusions, 70 remained in the IOLT group and 68 in the NIOLT group. In the IOLT group, 5 patients (7.1%) were found to have anastomotic defects intraoperatively, which included anastomotic discontinuity, bleeding, and strictures. The NIOLT group had a higher incidence of postoperative anastomotic leakage compared to the IOLT group: 4 patients (5.8%) vs 0 patients (0%), respectively. No GAM-related complications were observed. CONCLUSION: The GAM procedure is an intraoperative leak test that can be performed safely and efficiently after a laparoscopic total gastrectomy. GAM anastomotic leak testing may effectively prevent technical defect-related anastomotic complications in patients with gastric cancer who undergo a gastrectomy. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT04292496.