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.

Objective: To analyze the implementation status of the “Three-Exemptions” policy for voluntary blood donation in China by taking Shandong Province as a case study, explore the sociodemographic characteristics of policy beneficiaries and the distribution differences in blood donation frequencies, so as to provide practical references for improving the honor incentive system of voluntary blood donation and stabilizing the blood donation team. Methods: Excel was used to sort out and summarize the policy documents from 31 provincial-level administrative regions of China (excluding Hong Kong, Macao and Taiwan), and its implementation models, temporal characteristics and implementation basis were analyzed. Using 238 193 policy beneficiaries in Shandong Province as the research objects, Stata was adopted for descriptive statistical analysis of sociodemographic characteristics including gender, age, educational background and occupation. The Mann-Whitney U test and Kruskal-Wallis H test were performed to compare the distribution differences of blood donation frequencies among populations with different characteristics. Results: The “Three Exemption” policy has been implemented in 29 provinces nationwide, forming five differentiated implementation models. Specifically, 45.16% of the regions adopted province-wide unified implementation, 32.26% adopted partial prefecture-level city implementation, 12.90% adopted partial clause implementation, 3.23% adopted encouraging implementation, and 6.45% had not implemented the policy. The period from 2023 to 2026 witnessed the concentrated promotion of the policy. In Shandong Province, the beneficiaries were mainly males (82.08%), middle-aged individuals aged 40-60 years (71.78%), groups with junior and senior high school education (56.57%), and staff employees (30.60%). The distribution of blood donation frequencies showed that nearly 60% (56.95%) of the beneficiaries had donated blood 20 to 29 times. Statistically significant differences in donation frequency distributions were observed across genders, age groups, educational backgrounds, and occupations (all P<0.05). Further analysis revealed that the proportion of males with 40 or more blood donations was higher than that of females (24.32% vs 15.60%), while females had a higher proportion of 20-29 blood donations than males (65.98% vs 54.99%). With the increase of age, the proportion of those with 20-29 blood donations gradually decreased, whereas the proportion of those with≥40 blood donations gradually increased. Conclusion: The coverage of the “Three Exemptions” policy for voluntary blood donation in China continues to expand. However, there is still room for optimization in terms of policy implementation standards, population structure adaptation and incentive gradient design. Future efforts should strengthen national top-level design to balance regional development gaps. Moreover, hierarchical and targeted incentive and publicity strategies combined with population structural characteristics should be implemented to enhance public enthusiasm for voluntary blood donation.

Enhancer-promoter communication is fundamental to the spatial and temporal control of gene expression. Cohesin-mediated loop extrusion has long been considered a major structural mechanism that brings distal regulatory elements into proximity with their target promoters. Recent findings from Aboreden et al. refine this view by showing that depletion of Nipped-B-like protein (NIPBL), a key regulator of cohesin loading and loop extrusion, markedly disrupts architectural chromatin loops, whereas many cis-regulatory contacts and broad post-mitotic transcriptional reactivation are only modestly affected. These observations suggest that loop extrusion is important, but not sufficient, for explaining productive regulatory communication. In this Comment, we discuss how transcriptional condensate-like assemblies may provide an additional biochemical and kinetic layer that helps convert regulatory proximity into transcriptional output. By locally enriching transcription factors, coactivators, mediator and RNA polymerase II(Pol II) around active loci, such regulatory hubs may stabilize productive enhancer-promoter encounters and modulate transcriptional activity. We further propose that transcriptional bursting provides a useful framework for understanding this conversion, because gene expression can be decomposed into burst frequency, burst duration and burst size. Integrating chromatin architecture, condensate organization and bursting dynamics may therefore provide a more complete view of how enhancer-promoter communication is re-established after mitosis and how regulatory proximity is converted into transcriptional output through mechanisms beyond loop extrusion.

ObjectiveCurrently， evidence regarding whether the left or right nostril should be preferentially selected for nasotracheal intubation （NTI） in children remains insufficient， particularly under continuous visualization conditions. This study aimed to compare the efficiency and safety of NTI via the left versus right nostril in children under flexible intubation video endoscope （FIVE） guidance. MethodsA total of 100 children aged 3-7 years with American Society of Anesthesiologists physical status I-II， who were scheduled for elective dental caries treatment under general anesthesia， were randomly assigned to undergo FIVE-guided NTI via either the left nostril （group L） or the right nostril （group R）. The primary outcome was intubation time. Secondary outcomes included first-attempt success rate， number of intubation attempts， incidence and severity of epistaxis， peri-intubation hemodynamic and respiratory parameters， and postoperative procedure-related complications （nasal blockage， sore throat， and hoarseness）. ResultsNo statistically significant between-group difference was found in intubation time （L group： 36.86 ± 6.04 s vs. R group： 37.96 ± 6.20 s； P=0.371） or first-attempt success rate （96% vs. 92%， respectively； P=0.400）. The incidence and severity of epistaxis were comparable between groups （10% vs. 12%； P=0.749）. No statistically significant between-group differences were observed in hemodynamic and respiratory parameters at all measured time points （all P>0.05）. The incidences of postoperative nasal congestion， sore throat， and hoarseness were low in both groups. ConclusionIn children undergoing FIVE-guided NTI， tracheal catheter insertion via the left or right nostril yields comparable efficacy and safety. When using visualization-guided techniques in routine pediatric clinical practice， nostril laterality does not need to be prioritized when selecting the insertion side for NTI.

A 70-year-old female patient presented with fatigue and edema for 3 months and was found to have elevated serum creatinine for 3 weeks. During the course of the disease, she had fever and cough. Examinations revealed multiple ground-glass opacities in both lungs and positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibodies (ANCA), leading to a diagnosis of ANCA-associated vasculitis. The patient′s condition initially improved after pulse glucocorticoid therapy combined with cyclophosphamide. During treatment, however, the patient developed hematochezia, and colonoscopy revealed multiple colonic ulcers. Immunohistochemistry of colonic mucosal biopsy confirmed cytomegalovirus (CMV) positivity, establishing a diagnosis of CMV colitis. The patient was found to have concurrent Clostridioidesdifficile and pulmonary infections. During the disease course, the patient also developed deep vein thrombosis and roxadustat-associated central hypothyroidism. Given the presence of multiple comorbidities, rituximab was subsequently used for vasculitis treatment, resulting in sustained remission. This case highlights the importance of highly individualized treatment strategies for older patients with vasculitis, requiring adjustment of immunosuppressive therapy intensity based on disease progression.

Objective To observe the value of noninvasive right ventricular pressure-strain loop(RVPSL)for quantitative evaluation on right ventricular myocardial function changes in liver cirrhosis patients after TIPS.Methods Totally 26 cases of liver cirrhosis who would undergo TIPS were prospectively recruited as liver cirrhosis group.Echocardiography was performed before and 1 week,1 month after TIPS,and parameters of right ventricular myocardial function,including routine right ventricular echocardiography,right ventricular strain and right ventricular myocardial work were acquired.Meanwhile,30 healthy adults were recruited as control group,and the above parameters were recorded.Then these parameters were compared between groups,also before and after TIPS within liver cirrhosis group,and the changes of right ventricular myocardial function after TIPS were evaluated.Results Right ventricular global work index(RVGWI),right ventricular global constructive work(RVGCW)and right ventricular global wasted work(RVGWW)in liver cirrhosis group were higher than those in control group at all time points(all P＜0.05).One weak and 1 month after TIPS,right ventricular global longitudinal strain(RVGLS)and right ventricular free wall longitudinal strain(RVFWLS)in liver cirrhosis group were all higher than those in control group(all P＜0.05).In liver cirrhosis group,RVGWI,RVGCW and RVGWW 1 week after TIPS were all higher than those before TIPS and 1 month after TIPS(all P＜0.05),while RVGLS 1 weak and RVGWI 1 month after TIPS were both higher than those before TIPS(both P＜0.05).Conclusion Noninvasive RVPSL could be used to sensitively and quantitatively evaluate right ventricular function changes in patients with liver cirrhosis after TIPS.

Liquiritigenin(LG)is a flavone of pharmacological importance,however,its application potential is severely limited due to its poor water solubility.LG could be disassociated slightly in water to form phenolate anion,therefore,better solubilization effect is expected by inclusion with cationic cyclodextrins(CCDs).In this work,four kinds of CCDs modified with amino groups at the primary face were synthesized,and their solid inclusion complexes with LG were successfully prepared by preparing their saturated solutions.The formation of the solid inclusion complexes was confirmed by scanning electron microscopy(SEM)and powder X-ray diffraction(PXRD),and their supramolecular binding behavior in solution was studied using multiple techniques.A 1∶1 inclusion stoichiometry of inclusion complexation was defined using Job plot by ultraviolet-visible(UV-vis)spectroscopy,and their binding stability constants(Ks)were determined as 2862.77,3494.70,6521.85 and 9599.48 L/mol using UV-vis spectroscopic titration,far more superior to that of nativeβ-CD(Ks=236.79 L/mol).This indicated that the amino side chains on CCDs could actively participate in the inclusion complexation through anion-cation interactions,significantly strengthening the host-guest binding between CCDs and LG.The inclusion modes were further elucidated based on proton and two-dimensional rotating-frame overhauser enhancement spectroscopy(2D-ROESY)nuclear magnetic resonance(NMR)experiments and molecular docking.Water solubility of LG was dramatically promoted up to 4.9 mg/mL,which was 70-fold higher than that of native LG.This study could draw inspiration for the binding and solubilization of phenols such as flavones by design of cationic macrocyclic molecules.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.

Objective:To study the comprehensive surgical treatment of brucellosis with chest wall cysts as the main manifestation.Methods:Retrospective analysis was made on the general information epidemiological characteristics, clinical manifestations, laboratory examinations, imaging examinations, treatment and outcomes of five patients with brucellosis mainly manifested by chest wall cysts admitted to the 948 Hospital of the People's Liberation Army from July 2019 to June 2022.Results:Among the 5 patients, there were 4 males and 1 female, aged between 23 and 64 years old, with a clear history of contact with cattle and sheep. The main clinical manifestation was painless cystic masses on the chest wall. Both the serum tiger red plate agglutination test (RBPT) and the test tube agglutination test (SAT) were positive. Four cases were infected with Brucella and one case was infected with Actinobacillus pleuropneumoniae (considered as Brucella infection based on the overall condition). All patients exhibited abnormal chest wall signals (manifesting as hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging) on magnetic resonance imaging(MRI), and were ultimately diagnosed with brucellosis presenting predominantly as chest wall cysts. After complete removal of the chest wall cyst through surgery, a combination treatment of rifampicin capsules and doxycycline hyclate tablets was given for 6 weeks. There were no significant adverse reactions and the wound healed in one stage. During the postoperative follow-up period of 11 - 40 months, MRI reexamination demonstrated no evidence of chest wall cyst recurrence, and all SAT results were negative. Conclusions:Patients with brucellosis presenting as chest wall cysts are clinically rare and lack specific symptoms. Surgical resection of the affected lesion combined with early, standardized, combined, and full course antimicrobial therapy results in a good prognosis for the patient.