Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Background/Aims: Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods: Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results: All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral(16.42 ± 16.93 mmHg · cm to 31.95 ± 21.25 mmHg · cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg · s · cm to 1198.8 ± 811.74 mmHg · s · cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Dopamine, as a catecholamine neurotransmitter widely distributed in the central nervous system, is involved in physiological functions such as motivation, arousal, reinforcement, and movement through various dopamine signaling pathways. The hippocampus receives dopaminergic neuron projections from regions such as the ventral tegmental area, locus coeruleus, and substantia nigra. Through D1-like and D2-like receptors, dopamine exerts significant regulatory effects such as spatial navigation, episodic memory, fear, anxiety, and reward. This review mainly summarizes the research progress on the functions of dopamine in the hippocampus from aspects including the sources of dopamine, receptor distribution and function, and the association of hippocampal dopamine system dysregulation with neurodegenerative diseases. The aim is to provide insights into the involvement of the dopamine system in hippocampal functions and the diagnosis and treatment of related diseases.
Hippocampus/physiology* ; Dopamine/physiology* ; Humans ; Animals ; Receptors, Dopamine D2/physiology* ; Memory/physiology* ; Signal Transduction/physiology* ; Neurodegenerative Diseases/physiopathology*

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

OBJECTIVE: To explore the clinical efficacy and safety of the "Three-Step Nine-Method Lumbar Correction" combined with physical therapy in the treatment of patients with degenerative lumbar spondylolisthesis(DLS). METHODS: From January 2021 to December 2021, 72 patients diagnosed with DLS were enrolled and divided into the Three-Step Nine-Method Lumbar Correction group and the pelvic traction group, with 36 cases in each group. In the Three-Step Nine-Method Lumbar Correction group, there were 15 males and 21 females;aged 54 to 66 years old, with an average of (59.07±5.69) years old;the course of disease was 14 to 26 years old, with an average of (20.35±5.66) years old. They were treated with the Three-Step Nine-Method Lumbar Correction combined with low-frequency physical therapy, 3 times a week, for a 4-week course. In the pelvic traction group, there were 12 males and 24 females;aged 54 to 66 years old, with an average of (59.69±5.59) years old;the course of disease was 13 to 26 years old, with an average of (19.74±5.80) years old. They were treated with pelvic traction combined with low-frequency physical therapy. Efficacy evaluation was conducted using the visual analogue scale(VAS), Oswestry disability index(ODI), Japanese Orthopaedic Association (JOA) score, and Short Form 36 Health Survey (SF-36) before treatment, after 2 and 4 weeks of treatment, and at the 8-week follow-up after the end of treatment. In addition, imaging parameters of paravertebral muscles were evaluated before treatment and at the completion of treatment. RESULTS: All 72 patients completed the follow-up for 8 weeks. At the 8-week follow-up after the end of treatment, in the Three-Step Nine-Method Lumbar Correction group, the VAS score for low back pain decreased from (6.25±1.23) points before treatment to (1.25±0.65) points, with a statistically significant difference (P<0.05);the ODI decreased from (57.17±7.13)% before treatment to (19.89±5.66)%, with a statistically significant difference (P<0.05);the JOA score and SF-36 score increased from (15.46±3.20) points and (35.25±9.28) points before treatment to (23.75±2.10) points and (62.31±13.03) points, respectively, with statistically significant differences (P<0.05). The improvement of each index in the Three-Step Nine-Method Lumbar Correction group was better than that in the pelvic traction group (P<0.05), but the change in imaging parameters was not significant (P>0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05), and no serious adverse events occurred. CONCLUSION The Three-Step Nine-Method Lumbar Correction combined with physical therapy has a definite efficacy in the treatment of DLS. It can significantly relieve pain symptoms, improve physical function and patients' quality of life. Its effect is better than that of pelvic traction combined with physical therapy, and it has high safety. However, its improvement on paravertebral muscles is not obvious.
Humans ; Male ; Female ; Middle Aged ; Spondylolisthesis/physiopathology* ; Aged ; Prospective Studies ; Lumbar Vertebrae/physiopathology* ; Physical Therapy Modalities ; Adult

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Glucose transporters (GLUTs) are pivotal membrane proteins that facilitate the passive transport of glucose into cells. However, their aberrant overexpression is closely linked to the Warburg effect and chemotherapy resistance of tumors. GLUTs are complex multi-pass transmembrane proteins that require detergents for extraction from the cell membrane during preparation. The persistent presence of detergents in the sample can disrupt lipid-protein interactions, potentially leading to conformational distortion and functional losses of GLUTs, severely hindering the research into their structures and transport mechanisms. To eliminate detergent interference and preserve its authentic conformation, this study employs nanodisc technology and utilizes the self-assembly of the membrane scaffold protein MSP1E3D1 and phospholipids to produce a biomimetic membrane environment, thereby overcoming the limitations of conventional methods. The C-terminal His10-tagged GLUT1 was heterologously expressed in the insect cell Sf9/Bac-to-Bac system, and the GLUT1-nanodisc complex was obtained after detergent solubilization, affinity chromatography purification via anti-His antibody resin, and self-assembly. The successfully reconstituted nanodisc complex was further purified by Ni-NTA affinity chromatography. Nanodisc reconstitution produced monodisperse GLUT1 particles that retained native secondary structure, as confirmed by far-UV circular dichroism (CD) spectroscopy and dynamic light scattering (DLS). Unlike conventional detergent micelles, which lack a true lipid bilayer, distort transmembrane-helix topology, and occlude ligand-binding sites, the nanodisc platform embeds GLUT1 in a phospholipid bilayer that preserves its authentic conformation while eliminating detergent interference. The resulting GLUT1-nanodisc complex is therefore a superior scaffold for high-resolution cryo-EM structural analysis, permitting detailed interrogation of the transporter's conformational cycle, its interactions with partner proteins, and downstream structure-guided, high-throughput drug screening.
Nanostructures/chemistry* ; Glucose Transporter Type 1/biosynthesis* ; Humans ; Animals ; Phospholipids/chemistry* ; Detergents/chemistry*

Leonurine(SCM-198)was discovered as one of the active constituents of the Herba Leonuri(HL).Now it can be artificially synthesized.Several recent researches has proven that it exhibits anti-inflammatory effect in several systems in animal models and cell culture in vitro.The key mechanism involves downgrading the activity of nuclear transcription factor-κB(NF-κB),thereby inhibiting the phosphorylation of several signal pathways such as PI3K/Akt,MAPK,ERK,and JNK,or upregulating the activity of Nrf2 related pathways,resulting in downregulated expression of inflammatory cytokines such as tumor necrosis factor-α(TNF-α),IL-1β,IL-2,IL-6,IL-8,inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),chemokines,adhesion molecules,etc.Owing to the advantages of high safety and efficiency,the ease of administration,as well as its effectiveness in many organs and systems,leonurine has a widely prospect for future research and clinical applications.This article reviews the progress in the fundamental research of leonurine in multiple inflammation-related disease,and it could be expect to offer new possibilities for the treatment of these disease.