Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.

Effects of allergen immunotherapy on follicular regulatory T cells.

PURPOSE OF REVIEW: Emerging evidence indicating that the dysfunction of T follicular regulatory (T FR ) cells contributes to excessive immunoglobulin E (IgE) production and the development of allergic diseases. Conversely, allergen immunotherapy (AIT) modulates T FR cells abundance and function to promote immune tolerance. This review focus on the role of T FR cells in allergic diseases and AIT, with the objective of providing novel insights into the mechanisms underlying immune tolerance of AIT and proposing the potential targeting of T FR cells in the context of allergic diseases. RECENT FINDINGS: Numerous studies have consistently demonstrated that T FR cells play a pivotal role in the inhibition of class switch recombination to IgE in both humans and specific murine models. This suppression is attributed to the actions of neuritin and IL-10 secreted by T FR cells, which exert direct and indirect effects on B cells. In patients with allergic rhinitis, reduced frequencies of circulating or tonsillar T FR cells have been reported, along with impaired functionality in suppressing IgE production. AIT, whether administered subcutaneously or sublingually, reinstates the frequency and functionality of T FR cells in allergic rhinitis patients, accompanied by changes of the chromatin accessibility of T FR cells. The increase in T FR cell frequency following AIT is associated with the amelioration of clinical symptoms. SUMMARY: T FR cells exert an inhibitory effect on IgE production and demonstrate a correlation with the clinical efficacy of AIT in patients with allergic rhinitis, suggesting T FR cells hold promise as a therapeutic target for allergic diseases and potential biomarker for AIT.

Healthcare for Patients with Hepatitis B Virus: Analysis of 367 381 Inpatient Cases in China.

OBJECTIVE: Hepatitis B virus (HBV) infection, which has been recognized as an international public health challenge, has caused significant morbidity for the entire world. This research focused on patients with HBV in China to examine health utilization and expenses. METHODS: Patients hospitalized with HBV from 2017 to 2019 in tertiary hospitals in Hubei, a province located in central China, were selected as the study population. Healthcare information was collected from the provincial inpatient electronic system database. Univariate and regression analyses were performed to describe the basic situation of healthcare services and determine the influencing indicators of inpatient service expenditure. RESULTS: A total of 367 381 cases of HBV infection were identified in the study area. Most of these cases were patients who were married (90.2%) and males (63%). With the great efforts by the universal coverage of the basic medical insurance (BMI) in China, the increasing rate of inpatient hospitalization for HBV was 3.5 times higher than that of the total inpatient health service cases in the study area. The average age of this group was 52.84±14.10 years and 11.1% of patients paid for their own medical expenditures without insurance. The average length of stay (LOS) was 11.10 days, and the average cost per patient was 15 712.05 RMB. Both values were higher than the average level in study area. Gender, marital status, career, payment type, and kind of hospitals significantly influenced healthcare utilization. Males and the elderly might incur higher healthcare costs than their counterparts. CONCLUSION: The BMI operated by government has played a role in the utilization release of health services for HBV carriers. However, researchers must pay more attention to the continuing increase in the medical expenses of this group.

Predictive Value of BRAFV600E Mutation for Lymph Node Metastasis in Papillary Thyroid Cancer: A Meta-analysis.

BRAFV600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC). But whether BRAFV600E mutation is associated with lymph node metastasis (LNM) remains controversial. Different surgical strategies may bring a bias in demonsstrating the association between them. In order to delineate a risk stratification to guide a tailored initial approach to tumors that express BRAFV600E mutation, we performed this meta-analysis by using the articles in which total or near-total thyroidectomy plus bilateral central lymph node dissection was routinely performed to avoid the bias from the surgical strategy. We searched the Medline, Embase and CNKI database for eligible studies from January 2003 to May 2018. Meta-analysis was performed using the STATA 12.0 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under fixed-effects or randomeffects models. Fifteen clinical studies were included with a total of 4909 PTC patients. Our meta-analysis results reported that BRAFV600E mutation was associated with LNM (OR=1.34; 95% CI: 1.09-1.65; P=0.005), as well as central LNM (OR=1.59; 95% CI: 1.35-1.88; P<0.00001). Moreover, in patients with papillary thyroid microcarcinoma, we also confirmed the predictive value of BRAFV600E mutation for LNM (OR=3.49; 95% CI: 2.02-6.02; P<0.00001). This meta-analysis demonstrates that BRAFV600E mutation is closely related to LNM in PTC patients. The results suggest that BRAFV600E mutation can be considered as a risk factor for LNM in PTC. Moreover, combining BRAFV600E mutation with other risk factors to determine the initial surgical treatment may bring benefits for PTC patients.

Vegetable Oil Intake and Breast Cancer Risk: a Meta-analysis.

BACKGROUND: Total fat intake may be associated with increased risk of breast cancer, and fish oil has been suggested as a protection factor to breast cancer. But the effect of vegetable oils is inconclusive. We aimed to investigate the association with high vegetable oils consumption and breast cancer risk, and evaluated their dose-response relationship. DESIGN: We systematically searched the MEDLINE, EMBASE, Cochrane databases, and CNKI updated to December 2014, and identified all observational studies providing quantitative estimates between breast cancer risk and different vegetable oils consumption. Fixed or random effect models were used to estimate summary odds ratios for the highest vs. lowest intake, and dose-response relationship was assessed by restricted cubic spline model and generalized least-squares trend (GLST) model. RESULTS: Five prospective cohort studies and 11 retrospective case-control studies, involving 11,161 breast cancer events from more than 150,000 females, met the inclusion criteria. Compared with the lowest vegetable oils consumption, higher intake didn't increased the risk of breast cancer with pooled OR of 0.88 (95% CIs:0.77-1.01), and the result from dose- response analyses didn't show a significant positive or negative trend on the breast cancer risk for each 10 g vegetable oil/day increment (OR=0.98, 95% CIs: 0.95-1.01). In the subgroup analyses, the oils might impact on females with different strata of BMI. Higher olive oil intake showed a protective effect against breast cancer with OR of 0.74 (95% CIs: 0.60-0.92), which was not significant among the three cohort studies. CONCLUSIONS: This meta-analyses suggested that higher intake of vegetable oils is not associated with the higher risk of breast cancer. Olive oil might be a protective factor for the cancer occurrence among case-control studies and from the whole. Recall bias and imbalance in study location and vegetable oils subtypes shouldn't be ignored. More prospective cohort studies are required to confirm the interaction of the impact of vegetable oils on different population and various cancer characteristic, and further investigate the relationship between different subtype oils and breast cancer.

Effect of serum from overfatigue rats on JNK/c-Jun/HO-1 pathway in human umbilical vein endothelial cells and the intervening effect of Tongxinluo superfine powder.

OBJECTIVE: To cultivate human umbilical vein endothelial cells (HUVECs) in the serum of overfatigue rats with the intervention of Tongxinluo superfine powder (TXLSP). By examining the variation of the activity of JNK/c-Jun/HO-1 pathway, the possible mechanisms of vascular endothelial dysfunction under overfatigue conditions and the intervening effect of TXLSP were explored. METHODS: The HUVECs were randomly divided into the normal control group, the model group, the SP600125 (a specific antagonist of JNK) group, the TXLSP group and the TXLSP + SP600125 group. The content of carboyhemoglobin (COHb) and the leak rate of lactic dehydrogenase (LDH) in different groups were measured. The mRNA and protein expression of JNK, c-Jun, HO-1 and the phosphorylation level of c-Jun (P-c-Jun) were detected using Western blot and PCR methods. RESULTS: Compared with the normal control group, the COHb level in supernatant was increased significantly in the model group, and the expression of HO-1, JNK, c-Jun mRNA and corresponding proteins and P-c-Jun were also increased remarkably. The increases in these parameters were significantly decreased by SP600125. TXLSP showed remarkable up-regulation on the expression of JNK, c-Jun, P-c-Jun and HO-1 mRNA and their protein expression. Compared with the SP600125 group, the expressions of JNK, c-Jun, P-c-Jun and HO-1 mRNA and its protein in the TXLSP+SP600125 group were significantly increased at different time points (P<0.05, P<0.01). CONCLUSIONS: The vascular endothelial dysfunction under overfatigue conditions is related to the activity of the JNK/c-Jun/HO-1 pathway. One of the mechanisms of TXLSP in improving the vascular endothelial function is to adjust the activity of the JNK/c-Jun/HO-1 pathway at gene and protein levels.