Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

External fistula internalization - Endoscopic ultrasound guided stent implantation between stomach and fistula in the treatment of refractory pancreatic cutaneous fistula.

Pancreatic cutaneous fistula is a complex condition, making it challenging to achieve favorable outcomes with conservative medical treatment. Surgical interventions often entail surgical risks and postoperative complications. Here, we present a case involving endoscopically guided stent placement between the stomach and the fistula. By internalizing the fistula, patients can potentially remove the external drainage tube, offering a novel endoscopic treatment approach for such cases.

A polyoxometalate/chitosan-Ti3C2Tx MXene nanocomposite constructed by electrostatically mediated strategy for electrochemical detecting L-tryptophan in milk.

L-tryptophan (L-Trp) is crucial for human metabolism, and its imbalance or deficiency can lead to certain diseases, such as insomnia, depression, and heart disease. Since the body cannot synthesize L-Trp and must obtain it from external sources, accurately monitoring L-Trp levels in food is essential. Herein, a nanocomposite film based on polyoxometalate (P2Mo17V), Ti3C2Tx MXene, and chitosan (Cs) was developed through a green electrostatically mediated layer-by-layer self-assembly strategy for electrochemical detection of L-Trp. The composite film exhibits fast electron transfer and remarkable electrocatalytic performance for L-Trp with a wide linear range (0.1-103 µM), low limit of detection (0.08 µM, S/N = 3), good selectivity, reproducibility, and repeatability. In milk sample, the recoveries of L-Trp were from 95.78% and 104.31%. The P2Mo17V/Cs-Ti3C2Tx electrochemical sensor not only provides exceptional recognition and detection capabilities for L-Trp but also shows significant potential for practical applications, particularly in food safety and quality control.

Novel Circular RNA CircSLC2A13 Regulates Chicken Muscle Development by Sponging MiR-34a-3p.

The skeletal muscle is the major muscle tissue in animals, and its production is subject to a complex and strict regulation. The proliferation and differentiation of myoblasts are important factors determining chicken muscle development. Circular RNAs (circRNAs) are endogenous RNAs that are widely present in various tissues of organisms. Recent studies have shown that circRNA plays key roles in the development of skeletal muscles. The solute carrier (SLC) family functions in the transport of metabolites such as amino acids, glucose, nucleotides, and essential nutrients and is widely involved in various basic physiological metabolic processes within the body. In this study, we have cloned a novel chicken circular RNA circSLC2A13 generated from the solute carrier family 2 member 13 gene (SLC2A13). Also, circSLC2A1 was confirmed by sequencing verification, RNase R treatment, and reverse transcription analysis. Currently, our results show that circSLC2A13 promoted the proliferation and differentiation of chicken myoblasts. The double luciferase reporter system revealed that circSLC2A13 regulated the proliferation and differentiation of myoblasts by competitive binding with miR-34a-3p. In addition, results indicated that circSLC2A13 acts as a miR-34a-3p sponge to relieve its inhibitory effect on the target SMAD3 gene. In summary, this study found that chicken circSLC2A13 can bind to miR-34a-3p and weaken its inhibitory effect on the SMAD family member 3 gene (SMAD3), thereby promoting the proliferation and differentiation of myoblasts. This study laid foundations for broiler industry and muscle development research.

Improving denitrification estimation by joint inclusion of suspended particles and chlorophyll a in aquaculture ponds.

The denitrification process in aquaculture systems plays a crucial role in nitrogen (N) cycle and N budget estimation. Reliable models are needed to rapidly quantify denitrification rates and assess nitrogen losses. This study conducted a comparative analysis of denitrification rates in fish, crabs, and natural ponds in the Taihu region from March to November 2021, covering a complete aquaculture cycle. The results revealed that aquaculture ponds exhibited higher denitrification rates compared to natural ponds. Key variables influencing denitrification rates were Nitrate nitrogen (NO3--N), Suspended particles (SPS), and chlorophyll a (Chla). There was a significant positive correlation between SPS concentration and denitrification rates. However, we observed that the denitrification rate initially rose with increasing Chla concentration, followed by a subsequent decline. To develop parsimonious models for denitrification rates in aquaculture ponds, we constructed five different statistical models to predict denitrification rates, among which the improved quadratic polynomial regression model (SQPR) that incorporated the three key parameters accounted for 80.7% of the variability in denitrification rates. Additionally, a remote sensing model (RSM) utilizing SPS and Chla explained 43.8% of the variability. The RSM model is particularly valuable for rapid estimation in large regions where remote sensing data are the only available source. This study enhances the understanding of denitrification processes in aquaculture systems, introduces a new model for estimating denitrification in aquaculture ponds, and offers valuable insights for environmental management.

Preparation of bovine serum albumin-arabinoxylan cold-set gels by glucono-δ-lactone and salt ions double induction.

In order to investigate the effect of glucono-δ-lactone (GDL) and different salt ions (Na+ and Ca2+) induction on the cold-set gels of bovine serum albumin (BSA)-arabinoxylan (AX), the gel properties and structure of BSA-AX cold-set gels were evaluated by analyzing the gel strength, water-holding capacity, thermal properties, and Fourier Transform Infrared (FTIR) spectra. It was shown that the best gel strength (109.15 g) was obtained when the ratio of BSA to AX was 15:1. The addition of 1 % GDL significantly improved the water-holding capacity, gel strength and thermal stability of the cold-set gels (p < 0.05), and the microstructure was smoother. Low concentrations of Na+ (3 mM) and Ca2+ (6 mM) significantly enhanced the hydrophobic interaction and hydrogen bonding between BSA and AX after acid induction, and the Na+-induced formation of a denser microstructure with a higher water-holding capacity (75.51 %). However, the excess salt ions disrupted the stable network structure of the cold-set gels and reduced their thermal stability and crystalline structure. The results of this study contribute to the understanding of the interactions between BSA and AX induced by GDL and salt ions, and provide a basis for designing hydrogels with different properties.

[Retracted] Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the immunofluorescence data featured in Fig. 1H, TUNEL assay data in Fig. 2A, cytochome c leakage assay data in Fig. 2H, staining of cardiolipin images in Fig. 2H, lamellipodia­stained data in Fig. 3A, and immunofluorescence assay data in Figs. 3F and 5D were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Oncology Reports, or were under consideration for publication at around the same time (several of which have now been retracted). In addition, overlapping sections of data were noted within the data panels in Fig. 3D and F, such that data which were intended to represent the results from differently performed experiments had apparently been derived from the same original source(s). In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, and in view of an overall lack of confidence in the presented data, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 1671­1681, 2018; DOI: 10.3892/or.2018.6252].

Characterizing and identifying of miRNAs involved in berberine modulating glucose metabolism of Megalobrama amblycephala.

The present study, as one part of a larger project that aimed to investigate the effects of dietary berberine (BBR) on fish growth and glucose regulation, mainly focused on whether miRNAs involve in BBR's modulation of glucose metabolism in fish. Blunt snout bream Megalobrama amblycephala (average weight of 20.36 ± 1.44 g) were exposed to the control diet (NCD, 30% carbohydrate), the high-carbohydrate diet (HCD, 43% carbohydrate) and the berberine diet (HCB, HCD supplemented with 50 mg/kg BBR). After 10 weeks' feeding trial, intraperitoneal injection of glucose was conducted, and then, the plasma and liver were sampled at 0 h, 1 h, 2 h, 6 h, and 12 h. The results showed the plasma glucose levels in all groups rose sharply and peaked at 1 h after glucose injection. Unlike the NCD and HCB groups, the plasma glucose in the HCD group did not decrease after 1 h, while remained high level until at 2 h. The NCD group significantly increased liver glycogen content at times 0-2 h compared to the other two groups and then liver glycogen decreased sharply until at times 6-12 h. To investigate the role of BBR that may cause the changes in plasma glucose and liver glycogen, miRNA high-throughput sequencing was performed on three groups of liver tissues at 2 h time point. Eventually, 20 and 12 differentially expressed miRNAs (DEMs) were obtained in HCD vs NCD and HCB vs HCD, respectively. Through function analyzing, we found that HCD may affect liver metabolism under glucose loading through the NF-κB pathway; and miRNAs regulated by BBR mainly play roles in adipocyte lipolysis, niacin and nicotinamide metabolism, and amino acid transmembrane transport. In the functional exploration of newly discovered novel:Chr12_18892, we found its target gene, adenylate cyclase 3 (adcy3), was widely involved in lipid decomposition, amino acid metabolism, and other pathways. Furthermore, a targeting relationship of novel:Chr12_18892 and adcy3 was confirmed by double luciferase assay. Thus, BBR may promote novel:Chr12_18892 to regulate the expression of adcy3 and participate in glucose metabolism.

Case report: Phosphoinositide 3-kinase inhibitor with fulvestrant in a patient with ER+/HER2- metastatic breast carcinoma induced fatal arrhythmias: a preventable event?

Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was <500 and <60 ms at baseline) or choose other types of alternative treatment options. This report provided some ideas for clinicians to identify early and prevent the occurrence of fatal arrhythmias during anticancer treatment.

Nusinersen effectiveness and safety in pediatric patients with 5q-spinal muscular atrophy: a multi-center disease registry in China.

OBJECTIVE: To evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients. METHODS: Using a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results. RESULTS: As of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4-5.4) and 4.1 (2.8-5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7-3.1) and 2.3 (1.2-3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5-5.3) and 4.3 (2.6-6.0) in HFMSE, and 2.1 (1.2-3.0) and 1.5 (0.0-3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae. CONCLUSIONS: These data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance.

A study on the impact of icon structural features in human-computer interface on visual search efficiency.

This article, from the perspective of structural features, focuses on in-car user interface icons and explores the impact of different icon structural features on visual search efficiency. Initially, we categorised the icons into four groups based on structural features: individual structure icons (ISI), enclosed structure icons (ESI), horizontal structure icons (HSI) and vertical structure icons (VSI). Subsequently, we conducted a visual search experiment with structure as the sole variable, recording participants' behaviours and eye-tracking data. Finally, data analysis was conducted using methods including analysis of variance and logistic regression. The results indicate that differences in icon structural features significantly affect visual search efficiency, showcasing significant intergroup differences. HSI exhibit the highest visual search efficiency, while ESI show the lowest efficiency. ISI have shorter response times but the lowest matching accuracy. VSI only perform better than ESI. These findings hold significant implications for optimising icon design and enhancing visual search efficiency.

Visual search efficiency of icons is crucial for human-computer interaction. We investigated how the structural features of icons influence visual search efficiency. Horizontal icons are most effective, enclosed icons the least. Individual icons are quick but less accurate. Vertical icons outperform enclosed ones. Structural features should be considered in design.

Factors associated with pediatric ophthalmology follow-up adherence before and during the COVID-19 pandemic.

BACKGROUND: Studies describe poor follow-up among children in ophthalmology prior to the COVID-19 pandemic. Although the pandemic led to worse adherence for routine medical care in children, little information exists on pediatric ophthalmology follow-up adherence during COVID-19. The purpose of this study was to evaluate the effect of COVID-19 pandemic on follow-up adherence for children with eye disease, and identified characteristics associated with follow-up adherence. METHODS: In this single-center study, the medical records of 519 new pediatric (≤18 years of age) patients seen during January, April, August, and December 2019 and 2021 were reviewed retrospectively. Patients were classified into two groups: adherent (patients who followed up within 30 days of recommended appointment time) or less-adherent (patients who followed up >30 days after recommended follow-up or never). Main outcome measure was patient adherence status. RESULTS: Follow-up adherence was similar before and during the COVID-19 pandemic (50.4% for 2019 and 49.6% for 2021 [P = 0.40]). Patients that were less likely to be adherent in both univariate and multivariable analyses included those with public insurance (adjusted OR = 0.63 [95% CI, 0.40-1.00]; P = 0.05), and those recommended to follow-up ≥3 months (adjusted OR ≤ 0.10; P < 0.001). In addition, in univariate analysis, those who declined to self-report race (OR = 0.53 [95% CI, 0.29-0.95]; P = 0.04) and those seen by optometrists (OR = 0.42 [95% CI, 0.29-0.60]; P < 0.001) were less likely to be adherent, while patients who traveled ≥177 miles to their provider were more likely to be adherent (OR = 2.88 [95% CI, 1.17-7.55]; P = 0.02). CONCLUSIONS: Follow-up adherence for childhood eye care was low but remained relatively stable before and during the COVID-19 pandemic; >50% of children were less-adherent.

Simulated skin model for in vitro evaluation of insertion performance of microneedles: design, development, and application verification.

Microneedles, as a new efficient and safe transdermal drug delivery technology, has a wide range of applications in drug delivery, vaccination, medical cosmetology, and diagnostics. The degree of microneedles penetration into the skin determines the reliability of the delivery dose, but its evaluation is not yet well-established, which is one of the major constraints in the commercialization of microneedles. In this paper, a novel visual simulated skin model was developed with reference to the physical properties of real skin. The simulated skin model was well-designed and its prescription was optimized to make the thickness, hardness, elasticity, and other parameters close to those of real skin. It not only meets the need to assess the degree of insertion of microneedles but also provides a visual observation of the insertion state of microneedles.

Single-cell sequencing reveals the correlation of aggrephagy signaling and multiple myeloma immune microenvironment composition.

Aggrephagy, a type of autophagy, degrades the aggregation of misfolded protein in cells. However, the role of aggrephagy in multiple myeloma (MM) has not been fully demonstrated. In this study, we first investigated the correlation between aggrephagy signaling, MM immune microenvironment composition and disease prognosis. Single-cell RNA-seq data, including the expression profiles of 12,187 single cells from seven MM bone marrow (BM) and seven healthy BM samples, were analyzed by non-negative matrix factorization for 44 aggrephagy-related genes. Bulk RNA-seq cohorts from the Gene Expression Omnibus database were used to evaluate the prognostic value of aggrephagy-related immune cell subtypes and predict immune checkpoint blockade immunotherapeutic response in MM. Compared with healthy BM, MM BM exhibited different patterns of aggrephagy-related gene expression. In MM BM, macrophages, CD8+ T cells, B cells and natural killer cells could be grouped into four to nine aggrephagy-related subclusters. The signature of aggrephagy signaling molecule expression in the immune cells correlates with the patient's prognosis. Our investigation provides a novel view of aggrephagy signaling in MM tumor microenvironment cells, which might be a prognostic indicator and potential target for MM treatment.

Low-Friction Soft Robots for Targeted Bacterial Infection Treatment in Gastrointestinal Tract.

Untethered and self-transformable miniature robots are capable of performing reconfigurable deformation and on-demand locomotion, which aid the traversal toward various lumens, and bring revolutionary changes for targeted delivery in gastrointestinal (GI) tract. However, the viscous non-Newtonian liquid environment and plicae gastricae obstacles severely hamper high-precision actuation and payload delivery. Here, we developed a low-friction soft robot by assembly of densely arranged cone structures and grafting of hydrophobic monolayers. The magnetic orientation encoded robot can move in multiple modes, with a substantially reduced drag, terrain adaptability, and improved motion velocity across the non-Newtonian liquids. Notably, the robot stiffness can be reversibly controlled with magnetically induced hardening, enabling on-site scratching and destruction of antibiotic-ineradicable polymeric matrix in biofilms with a low-frequency magnetic field. Furthermore, the magnetocaloric effect can be utilized to eradicate the bacteria by magnetocaloric effect under high-frequency alternating field. To verify the potential applications inside the body, the clinical imaging-guided actuation platforms were developed for vision-based control and delivery of the robots. The developed low-friction robots and clinical imaging-guided actuation platforms show their high potential to perform bacterial infection therapy in various lumens inside the body.

Multi-dimensional niche differentiation of two sympatric breeding secondary cave-nesting birds in Northeast China using DNA metabarcoding.

Niche theory predicts that ecologically similar sympatric species should show differentiation in at least one of the main niche dimensions (time, space, and/or food). Here, we combined observations of breeding timing, nest site selection, and diet (the latter determined using DNA metabarcoding) to analyze the niche overlap and differentiation between two sympatric secondary cavity-nesting birds, the Japanese Tit Parus minor and the Yellow-rumped Flycatcher Ficedula zanthopygia. The results showed that (1) there were significant differences in the first egg laying date, length of the egg laying period, incubation date, and hatching date between tits and flycatchers, and the breeding time of flycatchers peaked later (about 30 days) than that of tits; (2) the two species had a large overlap in nest site selection, although the canopy coverage and shrub density of flycatchers were significantly higher than those of tits; and (3) the niche overlap in diet was minimal, with both species heavily relying on Lepidoptera (39.6% and 63.7% for tits and flycatchers, respectively), but with flycatchers consuming significantly higher percentages of Lepidoptera, Diptera, and Coleoptera than tits. The results indicate that these two sympatric secondary cavity-nesting species have significant niche differentiation in breeding time and diet, but little differentiation in nest site selection.

Recurrent Cerebral Venous Sinus Thrombosis Occurred in an Acute Lymphoblastic Leukemia Child with Mutated Lipoprotein Lipase Gene during Asparaginase Therapy.

Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.

Value of endoscopic grading of gastroesophageal flap valve in gastroesophageal reflux disease.

OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.