ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

BACKGROUND:Studies have found that nicotine can activate the dopamine system,slowing the progression of Parkinson's disease,but the specific mechanism is still unclear.Research on the neuroprotective mechanism of nicotine in animal models of Parkinson's disease is lacking. OBJECTIVE:To investigate the neuroprotective effect of nicotine on rotenone-induced Parkinson's disease in mice. METHODS:Twenty-eight C57BL/6 mice were randomly divided into vehicle group,rotenone group,autophagy agonist group and nicotine group,with seven mice in each group.Dopaminergic nerve damage was induced by rotenone in C57BL/6 mice,and the autophagy agonist(rapamycin)or nicotine was given before modeling.The spatial exploration function of the mice was observed by open field test.Western blot and Q-PCR were used to detect the expression of α-synuclein,autophagy related factors Beclin-1 and P62,and apoptosis-related factors Bax,Bcl-2 and Cleaved-caspase3 in the nigra of each group.The deposition of mitochondria,autophagosomes and lipofuscin in nigra cells were observed by transmission electron microscopy.The survival of neurons was observed by Nissl staining.The expression of tyrosine hydroxylase was observed by immunofluorescence and immunohistochemical staining. RESULTS AND CONCLUSION:The open field test showed that the distance,average speed and time of movement were reduced in the rotenone group compared with the solvent group.Compared with the rotenone group,the exercise distance,average speed and exercise time of mice were increased in the nicotine group and autophagy agonist group(P＜0.05).The results of immunofluorescence and immunohistochemistry showed that the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase in the rotenone group decreased compared with that in the solvent group.Compared with the rotenone group,the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase were increased in the nicotine group and autophagy agonist group.Western blot and Q-PCR results showed that compared with the solvent group,the expressions of α-synuclein and P62 in the rotenone group were increased,while Beclin-1 expression was decreased(P＜0.05);compared with the rotenone group,the expression of α-synuclein and P62 decreased in the nicotine group and autophagy agonist group,and the expression of Beclin-1 increased(P＜0.05).Compared with the solvent group,the expressions of Bax and Cleaved caspase3 were increased and Bcl-2 expression was decreased in the rotenone group(P＜0.05);compared with the rothenone group,the expressions of Bax and Cleaved-caspase3 were decreased and the expression of Bcl-2 was increased in the nicotine and autophagy agonist groups(P＜0.05).To conclude,nicotine may have a dopaminergic neuroprotective effect on rotenone-induced Parkinson's disease mouse models by improving autophagy dysfunction and reducing apoptosis.

Objective To identify the clinical characteristics and prognostic factors of young patients with sporadic rectal cancer liver metastasis(RCLM).Methods The clinical data of young RCLM patients at 45 years or under(n=40,as younger patient group)in Peking University First Hospital from January 2016 to January 2021 were reviewed,meanwhile,elder RCLM patient group were comprised of 82 patients older than 45-year-old in a 1:2 ratio.Proportions of categorical variables were compared between young patients and old patients.The clinicopathologic parameters were analyzed with univariate and multivariate Cox regression models and Kaplan-Meier method for demonstrating survival differences between the maximum diameter of liver metastasis and local therapy.Results One hundred and twenty-two RCLM patients were identified,the 1-,3-and 5-year survival rates of young patient group were 97.5%,47.5%,15.0%,those of elder patient group were 84.1%,26.8%,9.8%,respectively.The differences in BMI(P=0.008),primary tumor with obstruction and bleeding(P=0.006),synchronous rectal cancer liver metastases(P=0.005),the maximum diameter of liver metastasis>3 cm(P=0.019)were statistically significant between the two groups.And univariate and multivariate analyses showed that age(P=0.003),N stage(P=0.007),local therapy for liver metastases(P=0.047)and the maximum diameter of liver metastasis(P=0.030)were independent risk factors for influencing the prognosis of RCLM patients;curative resection or not of primary tumor(P=0.035)and the maximum diameter of liver metastasis(P=0.041)were independent risk factors for influencing the prognosis of young RCLM patients.Kaplan-Maier curve demonstrated survival differences between the maximum diameter of liver metastasis and local therapy for liver metastasis in RCLM patients(log-rank P=0.000).Conclusions Although with later staging of initial tumor station,young RCLM patients may obtain better survival benefit compared with old patients.Higher degree of lymph node metastasis,local therapy for liver metastases and the maximum diameter of liver metastasis>3 cm indicates poor prognosis in RCLM patients,and without curative resection of primary tumor and maximum diameter of liver metastasis are also considered as the independent poor prognostic factors of young RCLM patients.Local therapy for liver metastases appears to play an important role in the treatment strategy of RCLM patients.

Objective To analyze the risk factors for severe illness caused by coronavirus disease 2019 in Fuzhou city.Methods The data of 4081 confirmed cases with current address in Fuzhou was collected from China Information System for Disease Control and Prevention from January 1 to June 30,2023.The epidemiological data of those cases was investigated such as the demographic characteristics,clinical manifestations and past medical history,etc.The risk factors of severe cases were analyzed by using the logistic regression.Results 4081 confirmed cases had been reported including 671 severe cases and 3410 non-severe cases.The demographic characteristics of severe cases,such as the proportion of male,age and current address in community were higher than that of non-severe cases,vaccination rate was lower than non-severe cases(59.02%vs.80.12%),the differences are statistically significant(P＜0.001).The clinical manifestations such as interval time between onset and visit(P=0.001),fever(P=0.002),difficulty in breathing/shortness of breath(P=0.001)were the factors related to severe illness.The past medical histories such as history of chronic lung disease,history of heart cerebrovascular disease of severe cases,were higher than that of non-severe cases(P＜0.001).Multivariate logistic regression showed that the male,the higher age,current address in community,no vaccination,the longer interval time between onset and visit,fever,difficulty in breathing/shortness of breath,the history of chronic lung disease,the history of heart cerebrovascular disease raised the risk of becoming severe cases.The healing time for severe cases was longer than that for non-severe cases(P＜0.001).Conclusion Sex,age,current address,vaccination,interval time between onset and visit,fever,difficulty in breathing/shortness of breath,history of chronic lung disease,and history of heart cerebrovascular disease are the influencing factors for severe illness.

Objective We aimed to assess the serum levels of the glycolysis-related protein hypoxia-inducible factor-1α(HIF-1α)and cytokines in patients with relapsing-remitting multiple sclerosis(RRMS)before and after treatment with the traditional Chinese medicine Yishen Daluo Decoction,as well as their correlation with clinical parameters,and explore the immune regulatory mechanism of Yishen Daluo Decoction on multiple sclerosis.Methods Twenty-eight patients with RRMS in remission recruited from May 2018 to January 2022 in the Multiple Sclerosis Clinic at Dongzhimen Hospital,Beijing University of Chinese Medicine were retrospectively included.Comparisons were made with paired samples from 13 of them before and after Yishen Daluo Decoction treatment.A total of 20 gender-and age-matched healthy controls(HCs)were also recruited.Clinical information was collected from all of the subjects,and the neurological impairments of RRMS patients were assessed with the Expanded Disability Status Scale(EDSS)score.ELISA and SP-X multiplex cytokine assays were used to measure the serum levels of HIF-1 α and 10 cytokines(IL-1β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-22,IFN-γ,and TNF-α),respectively.Spearman's method was used to analyze the correlation between the serum levels of HIF-1α and cytokines,and the correlation between the serum levels of HIF-1α and cytokines and patients'clinical indicators,including disease duration,the number of attacks,and the EDSS score.Results Serum HIF-1α,IL-4,IL-6,IL-8,IL-10,IL-12p70,IFN-γ,and TNF-α levels in the RRMS group were significantly higher than those in the HC group(P＜0.05).Serum levels of HIF-1α,IL-4,IL-6,and IL-12p70 in the Yishen Daluo Decoction-pre group were significantly higher than those in the Yishen Daluo Decoction-post group(P＜0.05).In addition,the serum HIF-1α level was positively correlated with IL-6(r=0.452,P=0.016)and TNF-α(r=0.524,P=0.004)levels in patients with RRMS.The IFN-γ level was negatively correlated with the EDSS score(r=-0.423,P=0.025),the IL-4 level was negatively correlated with disease duration(r=-0.385,P=0.043),and the TNF-α level was positively correlated with disease duration(r=0.397,P=0.037).Conclusion The regulatory mechanism of Yishen Daluo Decoction on immune imbalance in RRMS may be related to its ability to reduce the serum levels of the glycolysis-related protein HIF-1α in RRMS patients.It is also related to the levels of various inflammatory cytokines.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.