Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

OBJECTIVE To preliminarily assess the horizontal sound localization and its influencing factors in patients with unilateral sudden sensorineural hearing loss during the acute phase.METHODS The azimuth discrimination test and azimuth identification test were completed,with the speech sound(65 dB SPL)as the stimulus.The minimum audible angle(MAA)and root-mean-square error(RMSE)were obtained,and the RMSE of the affected side and the healthy side were calculated respectively.According to the WHO(2021)hearing loss classification criteria,the data were analyzed based on the pure-tone average(PTA)of the affected ear.And the best resident hearing at each frequency of the affected ear was recorded.RESULTS The performance of the unilateral sudden sensorineural hearing loss patients in the sound localization varied greatly.Some performed close to the normal level,while others completely lost the ability to localize sound.The RMSE of the moderate hearing loss group(≥35 dB HL)was significantly higher than that of the normal hearing group(P<0.01),the MAA of the moderate to severe hearing loss group(≥50 dB HL)showed statistically significant differencescompared with normal hearing group(P<0.001).The RMSE of the affected side of patients in the severe and above hearing loss group was significantly larger than that of the healthy side.Regression analysis showed that the best resident hearing at each frequency of the affected ear was the most significant factor affecting MAA(R2=0.572,P<0.001)and RMSE(R2=0.768,P<0.001).CONCLUSION The horizontal sound localization of unilateral sudden sensorineural hearing loss patients in the acute phase varies greatly.When the PTA of the affected side reaches moderate hearing loss,the localization ability is significantly lower than that of normal-hearing individuals.The best resident hearing at each frequency of the affected ear is the key factor affecting the localization ability.

Autism spectrum disorder（ASD）is a multifactorial，pervasive neurodevelopmental disorder.As the morbidity rate of ASD in children increases year by year，feeding and eating behaviors，as an important and common clinical problem in children with ASD，are gaining more and more attention.Many children with ASD often have food selection issues，chewing problems，food allergy and related gastrointestinal symptoms，and even serious diseases such as eating disorders，which negatively impact on their growth and development.There are many factors affecting feeding and eating behavior problems in children with ASD，such as sensory processing，ritualistic eating behavior，gastrointestinal symptoms，age，and parenting pressure.There are also a variety of interventions that can help to improve feeding and eating behavior problems in children with ASD.Strengthening the understanding of these influencing factors and intervention treatment methods is beneficial for improving the quality of life in children with ASD.

Microsurgery is a surgical technique that applies fine instruments to perform precise operations on tiny tissues and organs under optical magnification devices. Digital and intelligent technologies, such as digital imaging, virtual reality (VR), augmented reality (AR), mixed reality (MR), 3D design and reconstruction, 3D printing, digital navigation, mixed perception of multi-source heterogeneous information, automatic control, digital twins, Internet of Things, cloud computing, machine learning, deep learning, large-scale AI models, generative artificial intelligence and so on, have been enabling the innovative development in microsurgery. It will make significant changes in disease diagnosis and monitoring, treatment decision-making and surgical planning, precise and individualised surgery, doctor-patient interaction and healthcare, team collaboration and professional education, and will drive the innovative development in microsurgery.

Objective:To explore the significance of genetic diagnosis, clinical characteristics and treatment of congenital renal diabetes insipidus with arginine vasopressin receptor 2 ( AVPR2). Methods:Clinical data of three patients diagnosed as diabetes insipidus were retrospectively analyzed.Results:The three cases were 3-month, 5-month and 6-month male infants, respectively. The main manifestations were repeated fever and growth retardation with hypernatremia. Polydipsia, polyuria and persistent hypogravity uria appeared during the course . In case 1, the AVPR2 exon c.613_c.614del resulted in amino acid change p.Y205Cfs*53. The proband mother was a mutation carrier of AVPR2 gene, and the child was hemizygous and the mother was heterozygous. In case 2, there was a hemizygotic mutation in AVPR2 gene: c.255C>A(p.SP85Glu), which appeared to be a missense mutation. The father had no mutation, the mother had a heterozygous mutation, the aunt had no mutation, and the eldest brother had a hemizygous mutation. There was one hemizygotic variation in the AVPR2 gene in patient 3: c.167G>A(P.LY56ASP), which was a missense mutation. The father had no mutation, the mother had a heterozygous mutation. The minimum allele frequencies of the gene variants in case 2 and case 3 were not recorded in the reference population gene frequency database. The urine volume of 3 children was significantly reduced after treatment with hydrochlorothiazide and amiloride.After genetic test, all three cases were diagnosed as congenital renal diabetes insipidus caused by AVPR2 gene mutation. Conclusion:Genetic testing benefits to the early diagnosis of congenital renal diabetes insipidus.

Objective To investigate the relationship between platelet distribution width(PDW)and coronary artery calcification(CAC)in overweight and obese populations.Methods Clinical and chest CT data of 10 838 subjects with overweight or obesity(body mass index[BMI]≥24 kg/m2)were retrospectively analyzed.The subjects were divided into CAC group(n=4 237)and non-CAC group(n=6 601)based on CAC scores obtained from chest CT.The relationship between PDW and CAC in overweight and obese populations was analyzed after controlling confounding variables.A threshold effect analysis was conducted using a two-stage logistic model to find the non-linear inflection point.Subgroup analyses and interaction tests were conducted to validate the stability of the relationship between PDW and CAC.Results Non-linear relationship was observed between PDW and CAC risk in overweight and obese populations.The risk of CAC decreased with the increase of PDW which ≤17.80％(OR=0.82),but increased with the increase of PDW(OR=1.04)which＞17.80％.Subgroup analysis showed that the relationship between PDW and CAC remained stable in subgroups of different genders,BMI(＜28 kg/m2,≥28 kg/m2)and hypertension(all P＞0.05).Compared with aged＜40 years or ≥60 years subgroups,under the same PDW,aged≥40 and＜60 years subgroups had higher risk of CAC(interaction P=0.015).Conclusion Nonlinear relationship existed between PDW and CAC in overweight and obese populations.Both excessively high and low PDW were risk factors of CAC.

AIM:To investigate the effects of emo-din on autophagy and apoptosis in rats with severe pneumonia(KP)caused by K.pneumoniae and its possible mechanism.METHODS:The KP rat model was established by infecting K pneumonia was treat-ed with Emodin.The rats were grouped into Sham surgery group,KP group,low concentration Emodin group,medium concentration Emodin group,high concentration Emodin group,and Emodin+sirtinol(SIRT1 activity inhibitor)group;Arterial partial pres-sure of carbon dioxide(PaCO2),arterial partial pres-sure of oxygen(PaO2)and arterial oxygen saturation(SaO2)were measured by blood gas analyzer;the white blood cells and neutrophils in bronchoalveo-lar lavage fluid(BALF)were measured by Wright-Gi-emsa staining;HE staining was applied to detect pathological changes in lung tissue in each group;ELISA was applied to detect the expression of IL-6,TNF-α,and IL-1β in lung tissues of each group;elec-tron microscopy scanning was applied to observe the autophagy of cells in lung tissues of each group;the expression of LC3B in lung tissues was observed by immunofluorescence staining;TUNEL method was applied to detect changes in cell apoptosis in lung tissue of rats in each group;Western blot was applied to detect the expression of silent informa-tion regulatory factor(SIRT1),adenosine monophos-phate activated protein kinase(AMPK),LC3-Ⅱ,LC3-Ⅰ,c-caspase-3,and caspase-3 proteins in lung tissue.RESULTS:K.pneumoniae caused severe lung tissue damage in rats with pneumonia,increased inflam-matory infiltration and cytokine release in the lungs,arterial blood PaO2 and SaO2 levels de-creased,PaCO2 levels increased,white blood cells and neutrophils count increased in BALF,increased cell apoptosis rate and c-caspase-3/caspase-3 level,and the cell autophagy and the levels of autophagy related proteins LC3-Ⅱ/LC3-Ⅰ were decreased(all P＜0.05),after Emodin treatment,SIRT1/AMPK signal-ing pathway was activated,PaO2 and SaO2 levels in arterial blood were increased,PaCO2 levels was de-creased,inflammatory reaction was inhibited,cell apoptosis in lung tissue was inhibited(all P＜0.05),and cell autophagy level was restored,sirtinol,a SIRT1 inhibitor,partially reversed the therapeutic ef-fect of Emodin on KP rats after inhibiting SIRT1/AMPK signaling pathway(P＜0.05).CONCLUSION:Emodin may enhance autophagy of lung tissue cells and inhibit apoptosis of rat lung tissue cells by acti-vating SIRT1/AMPK pathway,which may provide po-tential therapeutic options for KP.

In 2025,the International Association of Pancreatology(IAP),in collaboration with the American Pancreatic Association,European Pancreatic Club,Indian Pancreas Club,and Japan Pancreas Society,released the International Association of Pancreatology revised guidelines on acute pancreatitis 2025.This edition represents a comprehensive revision of the 2013 guidelines,based on high-quality evidence accumulated over the past decade,particularly randomized controlled trials.The guidelines encompass 18 key areas-including pain management,fluid therapy,nutritional support,management of infected necrosis,complication control,discharge and follow-up,and recurrence prevention-offering a total of 96 recommendations that emphasize individualized treatment.These updates provide important guidance for standardizing clinical practice and improving outcomes in acute pancreatitis,while also indicating future research directions such as the development of targeted therapies.However,some recommendations remain limited by lower evidence quality,uncertain applicability in specific clinical settings,and insufficient consideration of economic burden and cost-effectiveness.