Objective:To investigate the inhibitory effect of Xiaojianzhong Granule(XJZG)on food allergy(FA)and related mecha-nisms in terms of gut microbiota,zonula occluden-1(ZO-1),and Occludin.Methods:A total of 24 specific pathogen-free female BALB/c mice were randomly divided into normal group,model group,prevention group,and treatment group,with 6 mice in each group.The mice in the prevention group were given XJZG by gavage at a standard dose of 5.85 g/kg/day from 3 days before the first challenge till 4 hours before the last challenge;the mice in the treatment group were given XJZG at the double dose for 3 days based on the allergy score;the mice in the other groups were given an equal volume of distilled water by gavage.At the end of the experiment,al-lergy score and anal temperature were measured;flow cytometry was used to measure eosinophils and mast cells in mesenteric lymph nodes(MLNs);toluidine blue staining was performed for mast cells in jejunal tissue;immunohistochemistry was used to measure the expression of ZO-1 and Occludin;16S rRNA sequencing was per-formed to analyze the microbiota in the intestinal content;high-performance liquid chromatography-mass spectrometry was used to measure the content of short-chain fatty acids(SCFAs)in jejunal lavage fluid.Results:Compared with the model group,the prevention group and the treatment group had significant reductions in al-lergy score(P=0.000,P=0.000),anal temperature(P=0.002,P=0.000),the proportion of eosinophils and mast cells in MLNs(P<0.05),and mast cell infiltration in jejunal tissue(P=0.000,P=0.000).Compared with the normal group,the model group had signifi-cant increases in the relative abundances of Erysipelaceae and Turicibacter,while the prevention group and the treatment group had disappearance of Erysipelaceae and Turicibacter and an increase in the relative abundance of Porphyromonadaceae.Compared with the normal group,the model group had a significant reduction in the content of propionate in jejunal lavage fluid(P=0.014),and compared with the model group,the prevention group had a significant increase in the content of propionate in jejunal lavage fluid(P=0.024),as well as a significant increase in the treatment group(P=0.008).In the model group,the expression of ZO-1 was downregulated(P=0.010),and the expression of Occludin was significantly downregulated(P=0.002),while the expression of ZO-1 and Occludin re-turned to normal levels in the prevention group and the treatment group(P=0.001,P=0.013;P=0.025,P=0.015).Conclusion:XJZG can change the composition and abundance of gut microbiota,increase the concentration of SCFAs,upregulate the expression of ZO-1 and Occludin,promote the repair of intestinal barrier,and inhibit food allergy.

Objective: To compare the intervention effects of sitagliptin combined with metformin and insulin aspart combined with metformin among patients with type 2 diabetes mellitus (T2DM), so as to provide the reference for optimizing blood glucose control strategies among patients with T2DM. Methods: T2DM patients admitted to the department of endocrinology of Jinhua Central Hospital from January 2018 to December 2024 were selected as the research objects. According to the propensity score matching, T2DM patients were divided into sitagliptin combined with metformin group and insulin aspart combined with metformin group at a ratio of 1∶1. The basic information, capillary blood glucose, glycosylated hemoglobin blood glucose (HbA1c), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the two groups were collected by questionnaire survey, physical examination and laboratory test. The generalized estimating equation was used to analyze the changes of various indicators before and after treatment between the two groups of patients, and the intervention effect was compared. Results: There were 69 cases in the sitagliptin combined with metformin group. Among these 42 cases were males, accounting for 60.87%, and 27 cases were females, accounting for 39.13%.Forty-two cases were younger than 60 years, accounting for 60.87%. There were 69 cases in the insulin aspart combined with metformin group. Among these 47 cases were males, accounting for 68.12%, and 22 cases were females, accounting for 31.88%. Forty-five cases were younger than 60 years, accounting for 65.22%. There were no statistically significant differences in gender, age, education level, smoking, drinking, vegetable and fruit intake, and disease duration between the two groups (all P>0.05). After 6 months of treatment, there was an interaction between group and time in capillary blood glucose and HbA1c in the two groups (all P<0.05), and the reduction of capillary blood glucose and HbA1c in the sitagliptin combined with metformin group was greater than that in the insulin aspart combined with metformin group. There were no statistically significant differences between groups and time in TC, HDL-C, TG, BMI, SBP, and DBP, and no interaction effect was found between groups and time (all P>0.05). Conclusion Sitagliptin combined with metformin is more effective than insulin aspart combined with metformin in controlling blood glucose among patients with T2DM.

BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P  <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P  = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
Humans ; Neuroticism/physiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Surveys and Questionnaires ; Adult ; Risk Factors

Objective To investigate the current status of symptom burden and psychological distress among lung cancer patients in the diagnostic phase, and to explore the chain mediating role of social support and resilience between symptom burden and psychological distress. Methods The patients with lung cancer in the diagnostic phase who were treated in the Department of Thoracic Surgery of the Second Xiangya Hospital of Central South University from October 2022 to June 2023 were investigated by a general information questionnaire using the MD Anderson Symptom Inventory, the Social Support Rating Scale, the Connor-Davidson Resilience Scale, and the Distress Thermometer. The chain mediating role of social support and resilience between symptom burden and psychological distress was analyzed. Results A total of 413 lung cancer patients were enrolled, including 173 males and 240 females, aged (54.69±10.82) years. The detection rate of psychological distress among lung cancer patients in the diagnostic phase was 48.18%, and the average score was (3.84±2.50) points. Psychological distress was positively correlated with symptom burden (P<0.01), and negatively correlated with social support and resilience (P<0.01). The mediating effect of resilience between symptom burden and psychological distress was significant. The chain mediating effect of social support and resilience between symptom burden and psychological distress was also significant. Conclusion Lung cancer patients in the diagnostic phase have a high detection rate of psychological distress. Symptom burden can directly impact psychological distress, and can affect psychological distress through the indirect path of resilience as well as the chain mediating path between social support and resilience among lung cancer patients in the diagnostic phase.

Objective Based on 25 indicators including immune factors, cell count classification, and smear results of the knee joint fluid, machine learning models were established to distinguish between osteoarthritis (OA) and rheumatoid arthritis (RA). Methods 100 OA and 40 RA patients scheduled for total knee arthroplasty were enrolled respectively. Each patient's knee joint fluid was collected preoperatively. Nucleated cells were counted and classified. The expression levels of immune factors, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-8, IL-15, matrix metalloproteinase 3 (MMP3), MMP9, MMP13, rheumatoid factor (RF), serum amyloid A (SAA), C-reactive protein (CRP), and others were measured. Smears and microscopic classification of all the immune factors were performed. Independent influencing factors for OA or RA were identified using univariate binary logistic regression, Lasso regression, and multivariate binary logistic regression. Based on the independent influencing factors, three machine learning models were constructed which are logistic regression, random forest, and support vector machine. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to evaluate and compare the models. Results A total of 5 indicators in the knee joint fluid were screened out to distinguish OA and RA, which were IL-1β(odds ratio(OR)=10.512, 95× confidence interval (95×CI) was 1.048-105.42, P=0.045), IL-6 (OR=1.007, 95×CI was 1.001-1.014, P=0.022), MMP9 (OR=3.202, 95×CI was 1.235-8.305, P=0.017), MMP13 (OR=1.002, 95× CI was 1-1.004, P=0.049), and RF (OR=1.091, 95×CI was 1.01-1.179, P=0.026). According to the results of ROC, calibration curve and DCA, the accuracy (0.979), sensitivity (0.98) and area under the curve (AUC, 0.996, 95×CI was 0.991-1) of the random forest model were the highest. It has good validity and feasibility, and its distinguishing ability is better than the other two models. Conclusion The machine learning model based on immune factors in the knee joint fluid holds significant value in distinguishing OA and RA. It provides an important reference for the clinical early differential diagnosis, prevention and treatment of OA and RA.
Humans ; Arthritis, Rheumatoid/metabolism* ; Machine Learning ; Male ; Female ; Middle Aged ; Aged ; Synovial Fluid/immunology* ; Osteoarthritis, Knee/metabolism* ; Knee Joint/metabolism* ; ROC Curve ; Diagnosis, Differential

With the optimization of surgical technologies and postoperative management regimens, the number of lung transplantation has been significantly increased, which has become an important treatment for patients with end-stage lung disease. However, due to the impact of comprehensive factors, such as bronchial ischemia and immunosuppression, the incidence of airway stenosis after lung transplantation is relatively high, which severely affects postoperative survival and quality of life of lung transplant recipients. In recent years, with the improvement of perioperative management, organ preservation and surgical technologies, the incidence of airway stenosis after lung transplantation has been declined, but it remains at a high level. Early diagnosis and timely intervention play a significant role in enhancing clinical prognosis of patients with airway stenosis. In this article, the general conditions, diagnosis, treatment and prevention of airway stenosis after lung transplantation were reviewed, aiming to provide reference for comprehensive management of airway stenosis after lung transplantation and improving clinical prognosis of lung transplant recipients.

Objective:To explore the role of corticotrophin releasing factor receptor 2 (CRFR2) in regulating pain sensitization and anxiety and its mechanism in chronic migraine mice.Methods:Forty-eight C57BL/6J mice were randomly divided into control group, model group, NBI35965 group and K41498 group ( n=12); chronic migraine models in the later 3 groups were established by intraperitoneally administrating 10 mg/kg nitroglycerin on the 1 st, 3 rd, 5 th, 7 th and 9 th d; mice in the NBI35965 group and K41498 group were injected with 100 nL NBI35965 or K41498 solution into the bilateral trigeminal nucleus caudalis on the 2 nd, 4 th, 6 th and 8 th d, and mice in the control group were injected with same volume of normal saline. Von frey fiber was used to detect the orbitofrontal mechanical pain threshold 2 h after intraperitoneal injection on the 1 st, 3 rd, 5 th, 7 th and 9 th d, and at 11 a.m. on the 10 th d. Elevated plus maze was used to detect the anxiety-like behaviors at 11 a.m. on the 11 th d. Western blotting was performed to detect the protein expressions of corticotrophin releasing factor (CRF), corticotrophin releasing factor receptor 1 (CRFR1), CRFR2 in the trigeminal nucleus caudalis. Real-time quantitative PCR (RT-qPCR) was used to detect the CRFR1 and CRFR2 mRNA expressions in the trigeminal nucleus caudalis. Immunofluorescent staining was used to detect the protein expressions of calcitonin gene-related peptide (CGRP), immediate-early gene c-fos, glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) in the trigeminal nucleus caudalis. Results:Compared with the control group, the model group, NBI35965 group and K41498 group had significantly decreased orbitofrontal mechanical pain thresholds 3, 5, 7, 9, and 10 d after intraperitoneal injection ( P<0.05); compared with model group, the K41498 group had significantly increased orbitofrontal mechanical pain thresholds 7, 9, and 10 d after intraperitoneal injection ( P<0.05). Compared with control group, the model group, NBI35965 group and K41498 group had significantly decreased entries and shorter time in opened arms ( P<0.05); compared with the model group, the K41498 group had significantly increased entries and shorter time in opened arms ( P<0.05). Compared with the control group, the model group, NBI35965 group and K41498 group had significantly higher CRF and CRFR2 protein expressions in the trigeminal nucleus caudalis ( P<0.05); compared with the model group, the K41498 group had statistically lower CRF protein expression in the trigeminal nucleus caudalis ( P<0.05). Compared with the control group, the model group, NBI35965 group and K41498 group had significantly higher CRFR2 mRNA expression in the trigeminal nucleus caudalis ( P<0.05). Compard with the control group, the model group, NBI35965 group and K41498 group had significantly increased CGRP, c-fos, Iba-1 and GFAP protein expressions in the trigeminal nucleus caudalis ( P<0.05); compared with the model group, the K41498 group had significantly decreased CGRP and c-fos protein expressions in the trigeminal nucleus caudalis ( P<0.05). Conclusion:CRFR2 can alter the orbitofrontal pain sensitization and anxiety-like behaviors in chronic migraine mice by regulating neuronal activation and CGRP release in the trigeminal nucleus caudalis.

Objective:To investigate the safety of tocilizumab (TCZ) in the treatment of children with systemic juvenile idiopathic arthritis (sJIA).Methods:Data of children aged 2 to 18 years with the diagnosis of sJIA and treated with TCZ from June 1, 2017 to June 30, 2022 at our hospital were retrospectively collected. The clinical medication characteristics, incidence, severity and outcome of adverse drug reactions (ADR) were statistically analyzed. Univariate and multivariate analysis were used to analyze the risk factors of TCZ-induced ADR. Univariate comparison between groups were compared to the measured data followed by t test for normal distribution, and the counting data were paired with Chi-square test. Binary logistic regression analysis was used for multivariate analysis. Results:A total of 83 eligible children were enrolled. The age at TCZ initiation was (8.5±3.7) years old. Most of the children received oral glucocorticoid (86.8%) and/or methotrexate (72.3%) prior to TCZ treatment. The mean time of TCZ duration was (1.2±0.9) years, the total TCZ exposure was 92.70 patient years. Fifty-five (66.3%) children reported 123 ADR, with a rate of 132.69/100 patient years. Forty-two (50.6%) children reported 103 general ADR, with a rate of 111.11/100 patient years. Eighteen (21.7%) children reported 20 serious ADR, with a rate of 21.57/100 patient years. The results of univariate analysis showed that the dosage of glucocorticoid in ADR group was higher than that in non-ADR group [(0.76±0.50) mg·kg -1·d -1vs. (0.52±0.41) mg·kg -1·d -1, t=2.27, P=0.026], and the difference was statistically significant. However, there were no significant differences in gender [(male 23, female 32) cases vs. (male 9, female 19) cases, χ2=0.73, P=0.392], age at TCZ initiation [(8.5±3.8) years old vs. (9.0±3.1) years old, t=-0.65, P=0.516], duration of TCZ treatment [(1.24±1.00) years vs. (1.05±0.90) years, t=0.87, P=0.385], methotrexate doses weekly [(8.0±5.2) mg/m 2vs. (7.6±5.1) mg/m 2, t=0.39, P=0.696], and history of drug or food allergy (11 cases vs. 5 cases, χ2=0.06, P=0.815) between the two groups. The results of binary logistic regression analysis showed that the combined use of oral glucocorticoids was an independent risk factor for TCZ-induced ADR [ OR (95% CI) =3.05 (1.11, 8.36), P=0.030]. The risk of ADR was 3.05 times higher in the combined daily dose of glucocorticoids ≥0.76 mg/kg prednisone equivalent than that of < 0.76 mg/kg. Common general ADR to TCZ include infections (38.83/100 patient years) and abnormalities in laboratory parameters (37.76/100 patient years) such as elevated glutamic-pyrupiane transaminase (18.34/100 patient years), dyslipidemia (12.94/100 patient years), and hemocytopenia (5.39/100 patient years). The serious ADR included serious infection (9.71/100 patient years) and serious infusion reaction(7.55/100 patient years). All ADR were improved after drug withdrawal or symptomatic treatment, and no deaths occurred. Conclusion:TCZ has a good safety profile in the treatment of sJIA. Serious infections and severe infusion reactions often lead to discontinuation of the drug. The combination of glucocorticoids≥0.76 mg/kg prednisone equivalent is an independent risk factor for TCZ-induced ADR. Monitoring should be strengthened during the application of TCZ, and ADR should be detected and treated as early as possible to reduce the risk of medication related adverse reactions.

The survey on the hesitant status of rubella-containing vaccine (RCV) vaccination was conducted among 2 141 women of childbearing age in four provinces, Liaoning, Jiangsu, Zhejiang, and Anhui, from May 2017 to March 2018. Among the 2 141 study participants, a total of 38.21% (818) of women of childbearing age were aware of rubella and 21.25% (455) of women of childbearing age knew about RCV. Among the 455 women of childbearing age who were aware of RCV, 262 (57.58%) were willing to be vaccinated with RCV; 304 women of childbearing age (66.81%) tended to be vaccinated with RCV free of charge. Among the 193 women of childbearing age who did not want to be vaccinated or did not decide whether they preferred to be vaccinated with RCV, no one around them was vaccinated (89, 46.11%) and fear of vaccine safety (70, 36.27%) were the main reasons for hesitation to receive RCV.

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.