Irritable bowel syndrome （IBS） is a functional bowel disorder characterized primarily by abdominal pain and altered defecation habits. In recent years， traditional Chinese medicine （TCM） has made progress in multiple aspects of IBS research and treatment， including syndrome distribution， development of TCM formulas， clinical efficacy evaluation， external therapies， and psychosocial regulation. However， it still faces challenges such as over-reliance on symptomatic manifestations rather than biomarkers for diagnostic criteria， and the lack of high-quality evidence-based data supporting the efficacy of TCM formulas in treating IBS. This paper proposed that TCM diagnosis and treatment of IBS should adhere to the strategy of integrating the holistic concept with syndrome differentiation and treatment， combining TCM external therapies such as acupuncture， moxibustion and acupoint application）， and emphasizing individualized diagnosis and treatment for psychosomatic abnormalities. Future research should integrate multi-omics technologies， artificial intelligence and other methods to deepen the understanding of the pathogenesis of IBS and the mechanisms of TCM formulas， so as to promote the standardization and internationalization of TCM in the diagnosis and treatment of IBS.

Objective:To compare and analyze the application efficacy of active surveillance versus passive surveillance in post-marketing safety monitoring of the group A and C meningococcal polysaccharide vaccine(MPSV-AC).Methods:Safety data for MPSV-AC from its market launch in November 2011 to June 2024 were collected from Beijing Zhifei Lyuzhu Biopharmaceutical Co., Ltd., and categorized into active and passive surveillance data based on acquisition methods. Active surveillance data were derived from adverse events cases observed in the company′s phase Ⅳ clinical trial. Passive surveillance data were carried out by the Pharmacovigilance Department through the drug adverse reaction direct reporting system, which downloaded all adverse events following immunization(AEFI) case reports. Cases of adverse events under active surveillance that were "definitely related", "probably related", "possibly related", or "possibly unrelated" were classified as adverse reaction cases, and cases of passive surveillance that were classified as "general reaction" or "abnormal reaction" were classified as adverse reaction cases, and were counted according to the number of cases. For cases where different clinical manifestations of adverse reactions or preferred terminology were present in the same one patient, the number was counted separately. Descriptive epidemiological methods were used to describe the incidence of adverse reaction reports, the distribution of clinical manifestations, adverse reactions recorded and not recorded in the instructions and adverse reactions outcomes of two monitoring methods. The differences in the incidence of reported adverse reactions between active and passive surveillance were compared and analysed.Results:A total of 922 patients with MPSV-AC adverse reaction reports were obtained through two monitoring modes, and 1 308 adverse reactions were occurred. In the active surveillance, the number of vaccination doses was 9 999, and 579 patients with adverse reactions were reported with 911 adverse reactions. In the passive surveillance, the number of vaccination doses was 4 185 800, and 343 patients with adverse reactions were reported with 397 adverse reactions. The incidence of reported adverse reactions in the passive surveillance was lower than in the active surveillance, and the difference was statistically significant [0.008% (343/4 185 800) vs. 5.791% (579/9 999), P<0.001]. The age range for active surveillance was ≥2 to<7 years old; the age range of passive surveillance was 0-15 years old, with the highest proportion of those aged ≥2 to<7 years old [79.30% (273/343)]. The clinical manifestation that topped the composition ratio of major adverse reactions for both surveillanceme thods was fever, but systemic symptoms such as malaise and anorexia were more frequently reported in active surveillance, whereas signs visible on the surface such as allergic rash, erythema and hard nodules were reported in passive surveillance. The proportion of serious adverse reactions from active surveillance was 0.22%(2/922), which were upper respiratory tract infection and febrile convulsions. Of the adverse reactions not included in the specification, those from active surveillance mainly involved infections and invasive diseases [77.32% (75/97)], and those from passive surveillance mainly involved diseases of the skin and subcutaneous tissues(6/12). All 579 patients in the active surveillance adverse reaction reports were monitored until cured; in the passive surveillance, 199 cases (50.13%, 199/397) were cured, 168 cases (42.32%, 168/397) were improved, and 30 cases (7.56%, 30/397) were unknown. Conclusions:Active surveillance is irreplaceable for postmarketing safety evaluation of vaccines, as it comprehensively captures safety signals, indicating good safety of MPSV-AC. A multi-source data integration platform could be established in the future.

Objective:To identify the trajectories of dietary choline intake in middle-aged and older population, and to analyze its longitudinal association with cognitive function.Methods:Subjects aged 55 to 79 years with at least two rounds of completed population economics, lifestyle, disease history, cognitive function, dietary assessments and physical measurements in 1997-2018 and those with at least three rounds of dietary measures in 1991-2015 were selected from the China Health and Nutrition Survey. Dietary survey was conducted using three consecutive 24-hour dietary recalls combined with a weighing inventory at the household level. Cognitive assessment was performed using part of the Telephone Interview for Cognitive Status Scale. Group-based univariate trajectory modeling was used to identify trajectory of choline intake, and three-level linear mixed-effects models or three-level logistic mixed-effects models was employed to analyze the relationship between trajectory groups and cognitive function. Subgroup analyses were conducted by gender and age at baseline.Results:Four trajectories of dietary choline intake were identified in the whole population, named as low-intake-stable group (61.0%), medium-intake-stable group (23.9%), medium-intake-slowly-declined group (11.2%), and high-intake-stable group (3.9%). Three trajectories were identified for each subgroup. Low-intake-stable group accounted for more than 60% in total population as well as each subgroup, especially in women and 55-59 years group. After adjusting for covariates, global cognitive scores were 0.54 (95% CI: 0.26-0.82), 0.77 (95% CI: 0.36-1.18), and 0.85 (95% CI: 0.21-1.48) points higher in medium-intake-stable, medium-intake- slowly-declined and high-intake-stable groups in the whole population, respectively, compared with the low-intake-stable group. The likelihoods of cognitive decline were 18.4% ( OR=0.816,95% CI: 0.709-0.939), 17.6% ( OR=0.824, 95% CI: 0.680-0.998), 24.4% ( OR=0.756, 95% CI: 0.589-0.970) and 22.4% ( OR=0.776,95% CI: 0.623-0.968) lower in medium-intake-stable group of dietary choline in the whole population, medium-intake-stable group in males, medium-intake-slightly-increased group in females and medium-intake-slowly-increased group in 55-59 years at baseline than in low-intake-stable group, respectively. Conclusions:Dietary choline intake is generally lower in the Chinese population aged 55-79 years. Long-term lower choline intake has a negative impact on cognitive function in middle-aged and older adults and may increase the risk of cognitive decline. The increment in the consumption of choline-enriched foods should be recommended.

Objective:To explore the impact of different nutritional statuses on the prognosis of elderly patients with idiopathic pulmonary fibrosis(IPF), and to provide a basis for early intervention of the nutritional status of elderly IPF patients.Methods:A retrospective analysis was conducted on 237 elderly patients clinically diagnosed with IPF who were admitted to the First Hospital of Shanxi Medical University from January 2018 to May 2024.The GLIM criteria were applied to diagnose malnutrition and classify its severity.The patients were divided into two groups: those without nutritional risk(Group A)and those with nutritional risk(Group B). Group B was further subdivided into three subgroups: patients with only nutritional risk(Subgroup B1), those with moderate malnutrition(Subgroup B2), and those with severe malnutrition(Subgroup B3). The study observed the clinical characteristics of elderly IPF patients and the impact of nutritional factors on hospital admission frequency, activities of daily living(ADL), and all-cause mortality.Results:A total of 237 patients was included, with 129 patients(54.43%)in Group A and 108 patients(45.57%)in Group B. Among them, there were 34 patients(14.35%)in Subgroup B1, 57 patients(24.05%)in Subgroup B2, and 17 patients(7.17%)in Subgroup B3.The number of hospitalizations was significantly higher in both Group B and Subgroup B3 compared to Group A(both P < 0.05). However, no significant differences were found in the number of hospitalizations between Subgroup B1 or Subgroup B2 and Group A. There was no significant difference in the reduction of ADL between Group B(including all its subgroups)and Group A. The risk of mortality significantly increased with the increase in the severity of malnutrition(all P<0.05). After adjusting for factors such as gender, age, polypharmacy, home oxygen therapy, self-care ability, days of hospital stay, number of hospitalizations, pulmonary function, and inflammatory factors, nutritional risk and the degree of malnutrition remained independent risk factors for all-cause mortality in elderly IPF patients. Conclusions:A significant proportion of elderly IPF patients were found to have nutritional risk or malnutrition.The number of hospitalizations was significantly correlated with the nutritional status of these patients.After adjusting for multiple relevant factors, nutritional risk and the severity of malnutrition remained independent risk factors for mortality in elderly IPF patients.Therefore, greater emphasis should be placed on nutritional assessment and early nutritional intervention in the management of elderly IPF patients, so as to prevent and reduce the occurrence of nutrition-related adverse events.

As the first defense of respiratory system,airway epi-thelial cells(AECs)play an important role in separating the re-spiratory internal and external environment.They are essential for the natural immune function.Small airway lesions are an im-portant early pathology of chronic obstructive pulmonary disease(COPD),when AECs are exposed to harmful particles or gases for a long time,the epithelial barrier is damaged,and the signa-ling pathways which involved in differentiation,repair,and in-flammatory are disordered,resulting in epithelial cell cycle stag-nation and accelerated aging.A number of studies have sugges-ted that AECs of COPD patients express high levels of aging markers,suggesting that senescence of AECs is closely related to COPD.This review discusses the potential mechanisms of AECs senescence in COPD,the impact of AECs senescence on the de-velopment and severity of the disease,and highlights potential targets for modulating cellular senescence in airway epithelium as a therapeutic approach in COPD.

Aim To establish the pyroptosis model of rat chondrocytes induced by tumor necrosis factor α(TNF-α)in order to study the effect of lysine acetyl-transferase 7(KAT7)on pyroptosis of chondrocytes.Methods Chondrocytes of rat knee joint were isolated by type Ⅱ collagenase digestion,and were identified by toluidine blue staining and Col Ⅱ immunofluorescence.CCK-8 was used to evaluate cell viability.Western blot was used to detect the expression of pyroptosis-related proteins NLRP3,GSDMD,caspase-8 and KAT7 in cells intervened with TNF-α,adenovirus overexpression of KAT7(KAT7-oe)and KAT7 inhibitor WM-3835.The microstructure of the cells was observed by scanning e-lectron microscopy.Pyroptosis was detected by TUNEL staining,and the expression of pyroptosis-related pro-tein and KAT7 was detected by immunofluorescence.Results Compared with the empty virus group,KAT7-oe inhibited cell viability,promoted the expression of pyroptosis-related proteins,and TNF-α enhanced this effect.At the same time,the expression of KAT7 and pyroptosis-related proteins in the TNF-α stimulation group increased,and WM-3835 reduced the related proteins expression.Electron microscopy showed that KAT7-oe caused cell swelling,deformation,membrane perforation and rupture,while WM-3835 could restore cell morphology.TUNEL staining and immunofluores-cence results also confirmed that KAT7-oe induced chondrocyte pyroptosis,and WM-3835 could down-reg-ulate the fluorescence of pyroptosis-related proteins.Conclusions The expression of KAT7 increases in rat chondrocyte pyroptosis model,and the intervention of KAT7 expression affects signal molecules related to py-roptosis pathway,suggesting that KAT7 may be related to chondrocyte pyroptosis.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To investigate the characteristics and determinants of total scores of cerebral small vessel disease (CSVD) and to analyze the factors associated with enlarged perivascular space (EPVS) grading in pilots.Methods:The physical examination data of 72 pilots who were hospitalized and diagnosed with CSVD by MRI in the Air Force Medical Center (General Hospital of Air Force) between 2019 and 2022 was retrospectively analyzed. The pilots were grouped by the total CSVD score (0, 1, 2, 3, 4 points), and the distribution of CSVD imaging biomarkers was compared across groups. The severity of EPVS was classified into 3 levels: none or mild (0-10), moderate (11-20), and severe (>20). The impact of vascular risk factors on the total CSVD score and EPVS grading was analyzed.Results:The results of the total CSVD score showed that there were 19 cases (26.39%) with a score of 0, 43 cases (59.72%) with a score of 1, 10 cases (13.89%) with a score of 2, and 0 case with scores of 3 or 4. Among those who scored 1, there were 2 cases (4.65%) of lacunar infarction (LA), 1 case (2.33%) of moderate to severe white matter hyperintensity (WMH), 2 cases (4.65%) of cerebral microbleed (CMB), and 38 cases (88.37%) of moderate and severe EPVS. Among those who scored 2, there were 7 cases (70.00%) of LA combined with EPVS, 2 cases (20.00%) of CMB combined with EPVS, and 1 case (10.00%) of WMH combined with EPVS. According to the CSVD imaging classification of these pilots, there were 9 cases (12.50%) of LA, 52 cases (72.22%) of WMH, 4 cases (5.60%) of CMB and 61 cases (84.72%) of EPVS. Multiple ordered Logistic regression analysis showed that systolic blood pressure ( OR=1.068, 95% CI: 1.016-1.122) and high-density lipoprotein cholesterol ( OR=0.111, 95% CI: 0.015-0.843) made a difference in the total CSVD score. High-density lipoprotein cholesterol ( OR=0.166, 95% CI: 0.031-0.893) could affect the EPVS grading. Spearman′s correlation analysis showed that the systolic blood pressure level was positively correlated with the total CSVD score ( r=0.299, P=0.011), while the high-density lipoprotein cholesterol level was negatively correlated with the total CSVD score and EPVS grading ( r=-0.313, -0.263, P=0.041, 0.026). Conclusions:The total CSVD score of pilots is at a mild level with EPVS as the leading contributor. The systolic blood pressure and the high-density lipoprotein cholesterol level are determinants for the total CSVD score, while the high-density lipoprotein cholesterol level is a determinant for the EPVS grading of pilots. Blood pressure control and lipid regulation can go a long way towards preventing CSVD in pilots. The total CSVD score is of value for stratified evaluation and individual identification of pilots with CSVD.

Objective:To identify the trajectories of dietary choline intake in middle-aged and older population, and to analyze its longitudinal association with cognitive function.Methods:Subjects aged 55 to 79 years with at least two rounds of completed population economics, lifestyle, disease history, cognitive function, dietary assessments and physical measurements in 1997-2018 and those with at least three rounds of dietary measures in 1991-2015 were selected from the China Health and Nutrition Survey. Dietary survey was conducted using three consecutive 24-hour dietary recalls combined with a weighing inventory at the household level. Cognitive assessment was performed using part of the Telephone Interview for Cognitive Status Scale. Group-based univariate trajectory modeling was used to identify trajectory of choline intake, and three-level linear mixed-effects models or three-level logistic mixed-effects models was employed to analyze the relationship between trajectory groups and cognitive function. Subgroup analyses were conducted by gender and age at baseline.Results:Four trajectories of dietary choline intake were identified in the whole population, named as low-intake-stable group (61.0%), medium-intake-stable group (23.9%), medium-intake-slowly-declined group (11.2%), and high-intake-stable group (3.9%). Three trajectories were identified for each subgroup. Low-intake-stable group accounted for more than 60% in total population as well as each subgroup, especially in women and 55-59 years group. After adjusting for covariates, global cognitive scores were 0.54 (95% CI: 0.26-0.82), 0.77 (95% CI: 0.36-1.18), and 0.85 (95% CI: 0.21-1.48) points higher in medium-intake-stable, medium-intake- slowly-declined and high-intake-stable groups in the whole population, respectively, compared with the low-intake-stable group. The likelihoods of cognitive decline were 18.4% ( OR=0.816,95% CI: 0.709-0.939), 17.6% ( OR=0.824, 95% CI: 0.680-0.998), 24.4% ( OR=0.756, 95% CI: 0.589-0.970) and 22.4% ( OR=0.776,95% CI: 0.623-0.968) lower in medium-intake-stable group of dietary choline in the whole population, medium-intake-stable group in males, medium-intake-slightly-increased group in females and medium-intake-slowly-increased group in 55-59 years at baseline than in low-intake-stable group, respectively. Conclusions:Dietary choline intake is generally lower in the Chinese population aged 55-79 years. Long-term lower choline intake has a negative impact on cognitive function in middle-aged and older adults and may increase the risk of cognitive decline. The increment in the consumption of choline-enriched foods should be recommended.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.