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 evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Objective To analyze the characteristics of HIV-1 pretreatment drug resistance(PDR)and molecular transmission networks in Yubei District,Chongqing,providing evidence for targeted interventions.Methods Using a cross-sectional design,plasma samples were collected from HIV/AIDS patients receiving antiretroviral therapy(ART)in Yubei District from January 2022 to December 2023.Pol gene fragments were extracted and amplified for HIV-1 genotyping and drug resistance analysis.Molecular transmission networks were constructed based on genetic distance calculations.Results Among 478 HIV-1 pol sequences,eight geno-types were identified:with CRF07_BC(60.4%,289/478),CRF08_BC(15.5%,74/478),CRF01_AE(11.7%,56/478),and CRF85_BC(5.9%,28/478).The overall PDR rate was 6.3%(30/478),with resistance to nucleoside reverse transcriptase inhibitors(NRTIs)and non-nucleoside reverse transcriptase inhibitors(NNRTIs)at 1.7%(8/478)and 5.2%(25/478),respectively.No protease inhibitor(PI)resistance was de-tected.The molecular network included 177 cases(37.0%network entry rate),forming 53 clusters with 198 connections.Cluster sizes ranged from 2 to 17 nodes,and 75.3%(149/198)of connections were associated with five subdistricts/towns:Shuanglonghu Street,Huixing Street,Luoqi Town,Gulu Town,and Baoshenghu Street.Conclusion HIV-1 genotypes in Yubei District exhibit diversity and complexity,with moderate PDR prevalence.Regional clustering of transmission networks suggests the need for enhanced molecular surveil-lance and targeted interventions based on analytical findings.

A matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)method was developed for simultaneous analysis of 10 kinds of aphrodisiac drugs,including sildenafil,acetildenafil,nor-acetildenafil,homosildenafil,lodenafil carbonate,sildlenafil dimer impurity,vardenafil dimer,hydroxyacetildenafil,N-desmethylsildenafil and udenafil.By using different matrices(α-cyano-4-hydroxycinnamic acid(HCCA)and sinapic acid(SA)),the effects of solvents,amount of matrices,laser intensity and spotting methods on the peak strength and signal intensity of MALDI-TOF MS for the aphrodisiac drugs were investigated.As a result,SA was chosen as the matrix,and then dispersed in methanol-water(50∶50,V/V),and spotted by matrix firstly and sample secondly approach with the reflect linear positive mode and laser power of 60%.Under optimal conditions,the proposed MALDI-TOF MS method could obtain stable signal,high intensity and well-repeated mass spectrometric results.The results of method validation showed a linear range from 10 to 100 ng/mL,and the regression coefficients(r)were all above 0.985.The limits of detection(LOD)were 0.1-1.0 ng/mL,and the recoveries were in the range of 72.9%-109.9%for health wine,soft capsule and instant coffee samples,while the relative standard deviations(RSDs)ranged from 0.7%to 11.3%(n=3).The test results of 10 kinds of aphrodisiac drugs by MALDI-TOF MS were in accordance with the results of high-performance liquid chromatography-tandem mass spectrometry.This method exhibited high sensitivity,high accuracy,good anti-interference ability,low chemical solvents consumption and environmentally friendliness,and could be used to detect drugs without standards.The developed MALDI-TOF MS method could realize the non-target screening and detection of 10 kinds of illegally added aphrodisiac drugs in foods.

OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

This study aims to investigate the correlations of the appearance traits, total antioxidant capacity, and component content of Forsythiae Fructus processed by different methods, explore the effects of different processing methods on the abovementioned three aspects of Forsythiae Fructus, and screen out the internal and external indicators that have important effects on its quality. It determined the length, diameter, stem length, chroma value L~*, a~*, b~*, and other appearance indexes and antioxidant activity of Forsythiae Fructus processed by different methods. The content of forsythiaside A, rutin, forsythin, pinoresinol, and phillygenin was determined by ultra performance liquid chromatography(UPLC). Correlation analysis, principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and independent sample t-test analysis were performed on the appearance indexes and the component content. The correlation analysis showed that there were differences in the appearance traits and the component content. L~* and E~* had highly significant negative correlations with pinoresinol and phillygenin(P<0.01) and significant positive correlations with forsythiaside A(P<0.05). There were a highly significant negative correlation between a~* and forsythiaside A(P<0.01) and highly significant positive correlations of a~* with pinoresinol and phillygenin(P<0.01). There were a highly significant positive correlation between b~* and forsythiaside A(P<0.01) and highly significant negative correlations of b~* with pinoresinol and phillygenin(P<0.01). The total antioxidant capacity had highly significant negative correlations with pinoresinol and phillygenin(P<0.01). The PCA results showed that there were differences among Forsythiae Fructus samples processed by different methods. OPLS-DA marked five important indicators, which were forsythiaside A, stem length, E~*, L~*, and b~*. The results of independent sample t-test showed that the content of forsythiaside A, pinoresinol, and phillygenin, the total antioxidant capacity, and the appearance traits such as L~*, a~*, b~*, and E~* were significantly different between the Forsythiae Fructus samples processed by steaming and boiling(P<0.05). According to content determination and a related biological activity analysis, steaming is a good choice from the perspective of improving the stability of chemical constituents and antioxidant activity of Forsythiae Fructus. From the point of view of improving the stability of chemical constituents and anti-inflammatory and anti-cancer activities of Forsythiae Fructus, it is recommended to use boiling as the processing method. Based on the above analysis methods, the main indexes for the appearance traits of Forsythiae Fructus processed by different methods are powder chroma value(L~*, a~*, b~*, E~*), stem length, and total antioxidant capacity, and those for chemical constituents are the content of forsythiaside A, pinoresinol, and phillygenin. This study provides reference for seeking scientific processing methods of Forsythiae Fructus.
Forsythia/chemistry* ; Drugs, Chinese Herbal/isolation & purification* ; Fruit/chemistry* ; Antioxidants/analysis* ; Chromatography, High Pressure Liquid ; Glycosides/analysis* ; Principal Component Analysis ; Furans ; Lignans