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.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

Objective To explore the protective effect of hydroalcoholic extract of Portulaca oleracea L.(POHA)on ulcerative colitis(UC)and bone loss in mice.Methods The C57BL/6 mice were treated with dextran sulfate sodium(DSS)to establish UC model.A total of 50 mice were randomly assigned to including control group,DSS group,mesalazine(MS)group,low dose of POHA(POHAL)group,or high dose of POHA(POHAH)group.The control group freely drank drinking water,while the DSS,MS,POHAL and POHAH groups drank drinking water containing DSS for 8 weeks.Since the 2nd week,the control group and DSS group were given normal saline by gavage.The MS group was given MS(100 mg/kg)by gavage.The POHAL group and POHAH group were given POHA(1 000 mg/kg and 2 000 mg/kg)by gavage,respectively.Body weight and disease activity index(DAI)were recorded and calculated every 2 d.On the 56th day,the colon weight index,liver index,and spleen index were calculated,and the histological changes of colon were observed.Serum levels of bone metabolism markers and microstructure parameters of femur were detected.Results Compared with the control group,the DSS group showed significantly increased DAI score,colon weight index,liver index,and spleen index(all P＜0.01).The DSS group exhibited significant pathological damage in colon tissues and significantly increased serum levels of osteocalcin,C-terminal peptide of collagen type Ⅰ,and tartrate-resistant acid phosphatase 5b(P＜0.01).The bone loss was significant in the DSS group,manifested by markedly decreased bone mineral density(BMD),bone tissue volume to tissue volume ratio(BV/TV),trabecular bone number(Tb.N),and trabecular bone thickness(Tb.Th),and markedly increased bone surface to bone volume ratio(BS/BV)and trabecular bone separation(Tb.Sp)(P＜0.05 or P＜0.01).Compared with the DSS group,the BMD,BV/TV,Tb.N and Tb.Th of the femur in the MS group and POHAH group of mice were all increased(P＜0.05 or P＜0.01),the BS/BV all decreased(P＜0.05 or P＜0.01),and the Tb.Sp all decreased without significant differences(all P＞0.05).The above bone microstructure parameters in the POHAL group showed no significant differences compared with those in the DSS group(all P＞0.05).Conclusion POHA has protective effect on DSS-induced UC and bone loss,and the mechanism may be related to the inhibition of hyperactive bone metabolism.

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.

OBJECTIVE: To investigate the effect of traditional Chinese Five-body balance exercise on patients with preserved ratio impaired spirometry (PRISm). METHODS: Fifteen patients with PRISm and 15 patients diagnosed with chronic obstructive pulmonary disease (COPD) were recruited from the Outpatient Department of Guang'anmen Hospital and Beijing Niujie Health Service Center from April to December, 2023. Participants in both groups attended supervised Five-body balance exercise training twice a week for 12 weeks. Patients with COPD continued their regular medication regimen during the intervention period. The endpoints were mean changes in the 6-min walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ) score, cardiopulmonary exercise testing (CPET), pulmonary function, and scores of COPD assessment test (CAT), modified British Medical Research Council, Self-Rating Anxiety Scale, and Self-Rating Depression Scale from baseline to 12 weeks. Adverse events were monitored throughout the study. RESULTS: The PRISm group showed a significant improvement from baseline to week 12 in 6MWT, SGRQ symptom score, and forced vital capacity (FVC) compared to the COPD group (P<0.05). No significant between-group changes were observed in other outcome measurements (P>0.05). In addition, compared with baseline, both groups exhibited improvements in 6MWT, SGRQ score, and CPET at week 12 (P<0.05). The PRISm group also showed a significant increase in forced expiratory volume in 1 s and FVC, as well as a significant decrease in CAT score at week 12 (P<0.05). No adverse events were reported. CONCLUSION Patients with PRISm may benefit from Five-body balance exercise training, which can improve the exercise capacity, health-related quality of life, and lung function. (Registration No. ChiCTR2200059290).
Humans ; Spirometry ; Male ; Female ; Pulmonary Disease, Chronic Obstructive/therapy* ; Lung/physiopathology* ; Middle Aged ; Exercise Tolerance/physiology* ; Exercise Therapy ; Aged ; Medicine, Chinese Traditional ; Respiratory Function Tests ; East Asian People

Objective:To preliminarily explore the application of directional electrodes with perceivable subthalamic nucleus-deep brain stimulation (STN-DBS) for Parkinson′s disease (PD).Methods:A retrospective analysis was conducted on 56 patients with primary PD who underwent STN-DBS treatment across multiple neurosurgical centers, including the Department of Neurosurgery of the First Medical Center of the Chinese People′s Liberation Army General Hospital, the Department of Neurosurgery of Hua′an Brain Hospital Affiliated to Anhui Medical University, and the Department of Neurosurgery of Hefei Second People′s Hospital, from January to December 2024. The cohort included 26 patients in the directional+perception group and 30 in the conventional group. The directional+perception group had activation contacts selected based on electrode branch contact locations and local field potential data recorded by the perceptible deep brain stimulation (DBS) system. The conventional group used contact testing to determine therapeutic contacts. Unified Parkinson′s Disease Rating Scale-Ⅲ (UPDRS-Ⅲ) assessments were performed in the medication-off state under continuous STN-DBS therapy at postoperative activation, 1, 3, and 6 months, comparing postoperative data with preoperative baseline. Initial programming outcomes were also compared between groups.Results:By combining directional electrodes with sensing capabilities, therapeutic contacts can be selected more quickly and effectively. The directional+ perception group showed significantly shorter initial programming time compared to the conventional group [(30.1±4.7) min vs (65.0±6.8) min, respectively], with a statistically significant difference ( t=-22.159, P<0.001). Compared to preoperative baseline, UPDRS-Ⅲ scores improved markedly at postoperative activation and at 1, 3, and 6 months, with improvements of 59.8%(20.6±5.2 vs 51.2±8.7), 62.1%(19.4±6.2 vs 51.2±8.7), 55.5%(22.8±7.2 vs 51.2±8.7), and 61.7%(19.6±13.9 vs 51.2±8.7), respectively. The scores of tremor showed the greatest improvement of 72.2% [2.5(0, 4.3) vs 9.0(0, 13.0)], 61.1% [3.5(0, 5.0) vs 9.0(0, 13.0)], 72.2% [2.5(0, 5.0) vs 9.0(0, 13.0)], 63.3% [0(0, 3.3) vs 9.0(0, 13.0)], respectively, followed by rigidity. Axial symptoms, postural stability, and gait improved moderately, while speech showed no significant change. Conclusions:In the treatment of PD, the combined use of directional electrodes and a perceivable DBS system allows precise selection of therapeutic contacts. This approach not only safely and effectively improves patients′ motor symptoms but also significantly reduces the time required for initial programming compared to conventional DBS systems, demonstrating clear clinical advantages.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Senecavirus A (SVA) is a major viral pathogen causing disease in pigs, and effective monitoring of SVA infection is critical for disease control. In this study, we aimed to develop a reliable ELISA method for rapidly detecting neutralizing antibodies against SVA. We used HEK293F cells to express an SVA-specific porcine Fab antibody and verified the biological activity of the Fab antibody by indirect ELISA, immunofluorescence assay, virus neutralization test, and Western blotting. The Fab antibody was biotinylated and used as a competitive antibody to establish a competitive ELISA (C-ELISA) for detecting neutralizing antibodies against SVA. We then evaluated the C-ELISA in terms of sensitivity, specificity, repeatability, and result agreement rate with the VNT. The results showed that we successfully prepared an SVA-specific porcine Fab antibody, which showed high affinity for SVA. We named this antibody 1M33Fab and designated it as Bio-1M33Fab after biotin labeling. The assay conditions were optimized as follows: the coating concentration of SVA particles being 1 μg/mL, the working concentration of Bio-1M33Fab being 0.5 μg/mL, the optimal serum dilution of 1:10, and the optimal dilution of enzyme-labeled avidin being 1:30 000. At a percent inhibition (PI) of 47%, the assay demonstrated the highest sensitivity (96.88%) and specificity (100%), with no cross-reactivity observed with the positive sera of major porcine viral diseases. The intra-assay coefficient of variation ranged from 1.12% to 7.34%, while the inter-assay coefficient of variation ranged from 1.10% to 8.97%, indicating good repeatability. In the detection of 224 clinical pig serum samples, C-ELISA and VNT showed a result agreement rate of 93.75%. In conclusion, we successfully develop a C-ELISA method for detecting neutralizing antibodies against SVA by using a porcine-derived Fab antibody, which lays a foundation for the development of detection kits.
Animals ; Swine ; Antibodies, Neutralizing/immunology* ; Enzyme-Linked Immunosorbent Assay/methods* ; Immunoglobulin Fab Fragments/immunology* ; Antibodies, Viral/immunology* ; Picornaviridae/immunology* ; Humans ; HEK293 Cells ; Swine Diseases/diagnosis* ; Picornaviridae Infections/diagnosis*