Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis.

Acupuncture is one of the most effective complementary therapies for allergic rhinitis (AR) and has been recommended by several clinical practice guidelines (CPGs) for AR. However, these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols, therefore limiting the applicability of acupuncture therapies for AR. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat AR. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method. The CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions. These include one strong recommendation for the intervention based on high-quality evidence, three conditional recommendations for either the intervention or standard care, and 11 conditional recommendations for the intervention based on very low quality of evidence. The CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Du SH, Chen S, Wang SZ, Wang GQ, Du S, Guo W, Xie XL, Peng BH, Yang C, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis. J Integr Med. 2024; Epub ahead of print.

Multiple dietary patterns and the association between long-term air pollution exposure with type 2 diabetes risk: Findings from UK Biobank cohort study.

BACKGROUND: Evidence of modifying effect of various dietary patterns (DPs) on risk of type 2 diabetes (T2D) induced by long-term exposure to air pollution (AP) is still rather lacking, which therefore we aimed to explore in this study. METHODS: We included 78,230 UK Biobank participants aged 40-70 years with at least 2 typical 24-hour dietary assessments and without baseline diabetes. The annual average concentration of particulate matter with diameter micrometers ≤2.5 (PM2.5) and ≤10 (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX) estimated by land use regression model was the alternative proxy of long-term AP exposure. Three well-known prior DPs such as Mediterranean diet (MED), dietary approaches to stop hypertension diet (DASH), and empirical dietary inflammatory pattern (EDIP), as well as three posterior DPs derived by the rank reduced regression model were used to capture participants' dietary habits. Cox regression models were used to estimate AP-T2D and DP-T2D associations. Modifying effect of DPs on AP-T2D association was assessed using stratified analysis and heterogeneity test. RESULTS: During a median follow-up 12.19 years, 1,693 participants developed T2D. PM2.5, PM10, NO2, and NOX significantly increased the T2D risk (P <0.05), with hazard ratio (HR) and 95% confidence interval (95% CI) for per interquartile range increase being 1.09 (1.02,1.15), 1.04 (1.00, 1.09), 1.11 (1.04, 1.18), and 1.08 (1.03, 1.14), respectively. Comparing high with low adherence, healthy DPs were associated with a 14-41% lower T2D risk. Participants with high adherence to MED, DASH, and anti-EDIP, alongside the posterior anti-oxidative dietary pattern (AODP) had attenuated and statistically non-significant NO2-T2D and NOX-T2D associations (Pmodify <0.05). CONCLUSIONS: Multiple forms of healthy DPs help reduce the T2D risk associated with long-term exposure to NO2 and NOX. Our findings indicate that adherence to healthy DPs is a feasible T2D prevention strategy for people long-term suffering from NO2 and NOX pollution.

Acupuncture treatment for Hashimoto's thyroiditis: An exploratory randomized controlled trial.

Background: Hashimoto's thyroiditis (HT) has a high incidence rate and unresolved clinical symptoms. Although Hand Yangming Meridian Penetrating Acupuncture has been used to treat thyroid diseases in China, there is no randomized controlled trial (RCT) on HT. Methods: This exploratory RCT aims to preliminarily evaluate the efficacy, safety, and feasibility of Hand Yangming Meridian Penetrating Acupuncture in the treatment of HT. Included subjects were randomly assigned to the acupuncture group and the waiting treatment group at a ratio of 1:1. Subjects in the acupuncture group received 16 weeks of acupuncture treatment, followed by a 16-week follow-up observation phase. Subjects in the waiting group received thyroxine supplementation for 16 weeks, followed by 16 weeks of compensation treatment. Serum thyroid peroxidase antibody (TPOab) and thyroglobulin antibody (TGab) levels were the main indicators, and Thyroid-Related Patient-Reported Outcome short form (ThyPRO-39), MOS Item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS) scores were also recorded. Results: In total, 58 subjects were included. After 16 weeks of treatment, there was no statistical difference in the changes in TPOab levels between the two groups, but the TGab level in the acupuncture group was significantly lower than in the waiting group (difference: -141.97 [95 % CI: -222.4 to -61.5], P = 0.011). Moreover, the total ThyPRO-39 and SF-36 scores were statistically different between the two groups (PThyPRO-39 < 0.001, PSF-36 = 0.005). There was no statistical difference in HADS between the two groups. Conclusions: Hand Yangming Meridian Penetrating Acupuncture may be safe and feasible for HT hypothyroidism to improve symptoms and reduce TGab levels. Trial registration number: This trial was registered at Acupuncture-Moxibustion Clinical Trial Registry: AMCTR-IOR-19000308 (ChiCTR1900026830, https://www.chictr.org.cn/searchprojEN.html).

FGAHOI: Fine-Grained Anchors for Human-Object Interaction Detection.

Human-Object Interaction (HOI), as an important problem in computer vision, requires locating the human-object pair and identifying the interactive relationships between them. The HOI instance has a greater span in spatial, scale, and task than the individual object instance, making its detection more susceptible to noisy backgrounds. To alleviate the disturbance of noisy backgrounds on HOI detection, it is necessary to consider the input image information to generate fine-grained anchors which are then leveraged to guide the detection of HOI instances. However, it has the following challenges. i) how to extract pivotal features from the images with complex background information is still an open question. ii) how to semantically align the extracted features and query embeddings is also a difficult issue. In this paper, a novel end-to-end transformer-based framework (FGAHOI) is proposed to alleviate the above problems. FGAHOI comprises three dedicated components namely, multi-scale sampling (MSS), hierarchical spatial-aware merging (HSAM) and task-aware merging mechanism (TAM). MSS extracts features of humans, objects and interaction areas from noisy backgrounds for HOI instances of various scales. HSAM and TAM semantically align and merge the extracted features and query embeddings in the hierarchical spatial and task perspectives in turn. In the meanwhile, a novel training strategy Stage-wise Training Strategy is designed to reduce the training pressure caused by overly complex tasks done by FGAHOI. In addition, we propose two ways to measure the difficulty of HOI detection and a novel dataset, i.e., HOI-SDC for the two challenges (Uneven Distributed Area in Human-Object Pairs and Long Distance Visual Modeling of Human-Object Pairs) of HOI instances detection. Experiments are conducted on three benchmarks: HICO-DET, HOI-SDC and V-COCO. Our model outperforms the state-of-the-art HOI detection methods, and the extensive ablations reveal the merits of our proposed contribution.

[From the body-mind holism to psychosomatic medicine: theory and practice of acupuncture and moxibustion].

The traditional life concept of "body-mind holism" in Chinese medicine has drawn a special attention with the development of modern psychosomatic medicine. The "body-mind holism" is valuable in the guidance for clinical acupuncture practice, but, it is only remained on the theoretical significance by the medical masters in the past dynasties. In the paper, based on the understanding of Huangdi Neijing (Yellow Emperor's Internal Classic), the similarities and differences are compared between the body-mind theory and psychosomatic medicine. In association with clinical observation, from three aspects, i.e. body-mind pathogenesis, acupoint detection and observing the mind, and body-mind treatment, the guidance of "body-mind holism" is explored for the clinical diagnosis and treatment of acupuncture and moxibustion; the referents of "body" and "mind" are clarified in views of disease, diagnosis and treatment; and the treatment strategies of acupuncture and moxibustion are discussed in the perspective of "body-mind holism".

Alpha peak activity in resting-state EEG is associated with depressive score.

Introduction: Depression is a serious psychiatric disorder characterized by prolonged sadness, loss of interest or pleasure. The dominant alpha peak activity in resting-state EEG is suggested to be an intrinsic neural marker for diagnosis of mental disorders. Methods: To investigate an association between alpha peak activity and depression severity, the present study recorded resting-state EEG (EGI 128 channels, off-line average reference, source reconstruction by a distributed inverse method with the sLORETA normalization, parcellation of 68 Desikan-Killiany regions) from 155 patients with depression (42 males, mean age 35 years) and acquired patients' scores of Self-Rating Depression Scales. We measured both the alpha peak amplitude that is more related to synchronous neural discharging and the alpha peak frequency that is more associated with brain metabolism. Results: The results showed that over widely distributed brain regions, individual patients' alpha peak amplitudes were negatively correlated with their depressive scores, and individual patients' alpha peak frequencies were positively correlated with their depressive scores. Discussion: These results reveal that alpha peak amplitude and frequency are associated with self-rating depressive score in different manners, and the finding suggests the potential of alpha peak activity in resting-state EEG acting as an important neural factor in evaluation of depression severity in supplement to diagnosis.

The Obesity-Related Dietary Pattern Is Associated with Higher Risk of Sleep Disorders: A Cross-Sectional Study from NHANES.

Evidence on the association between dietary patterns and sleep disorders is limited and controversial. In addition, studies evaluating the effect of dietary patterns on sleep disorders have seldom considered the critical role of obesity. We aimed to explore obesity-related dietary patterns and evaluate their impact on sleep disorders using data from the National Health and Nutrition Examination Survey 2005-2014. In total, 19,892 participants aged over 20 years with two-day dietary recalls were enrolled. Obesity-related dietary patterns explaining most variance in waist circumference and BMI simultaneously were extracted from twenty-six food groups by the using partial least squares method. Sleep disorder and sleep duration, which were defined by self-reported questions, were the primary and the secondary outcome, respectively. Generalized linear models were performed to estimate the association of sleep disorders and sleep duration with dietary patterns. Two types of dietary patterns were identified. The "high fats, refined grains, and meat" pattern was characterized by high intakes of solid fats, cured meat, potatoes, refined grains, meat, cheese, and added sugars. The "low whole grains, vegetables, and fruits" pattern was characterized by low intakes of oils, whole grains, nuts and seeds, milk, fruits, and several vegetables. Participants with the highest adherence to the "high fats, refined grains, and meat" pattern had a higher risk for sleep disorders (OR (95%CI): 1.43 (1.12, 1.84)) and shorter sleep duration (ß (95%CI): -0.17 (-0.26, -0.08)) compared to those with the lowest adherence. The corresponding associations for the "low whole grains, vegetables, and fruits" pattern were only significant for sleep duration (ß (95%CI): -0.26 (-0.37, -0.15)). Our results found that the dietary pattern characterized by high solid fats, cured meat, potatoes, refined grains, meat, cheese, and added sugars, was associated with a higher risk for sleep disorders and shorter sleep duration.

[Effect of acupuncture intervention at different time points on the pregnancy rate of frozen embryo transfer].

OBJECTIVE: To observe the difference in the efficacy of acupuncture intervention at different time points on the pregnancy rate of in vitro fertilization-frozen embryo transfer (IVF-FET). METHODS: Ninety-nine patients with secondary infertility who were going to receive IVF-FET were divided into a transplantation-day acupuncture group, a transplantation cycle acupuncture group, and a non-acupuncture group according to their wishes, with 33 cases in each group. All three groups of patients received conventional IVF-FET treatment. The transplantation-day acupuncture group received acupuncture treatment 1 h before and 30 min after the embryo transfer, and the transplantation cycle acupuncture group received acupuncture treatment 5 weeks before the FET (once a week, 5 times) and on the day of transplantation, Zigong (EX-CA 1), Guanyuan (CV 4), Taichong (LR 3), Hegu (LI 4), etc. were selected in the two groups. The biochemical pregnancy rate and clinical pregnancy rate in the three groups were compared. RESULTS: The biochemical pregnancy rate and clinical pregnancy rate in the transplantation cycle acupuncture group were higher than those in the non-acupuncture group (P<0.05). There was no statistical difference in the biochemical pregnancy rate and clinical pregnancy rate between the transplantation cycle acupuncture group and the transplantation-day acupuncture group, and between the transplantation-day acupuncture group and the non-acupuncture group (P>0.05). CONCLUSION: Acupuncture during the transplantation cycle can effectively improve the pregnancy rate of secondary infertility patients receiving IVF-FET.

[Using modified Delphi method to determine the clinical questions in the Practice Guideline of Acupuncture and Moxibustion for Urinary Incontinence in Women].

With the expert consensus during the clinical questions determination in the World Federation of Acupuncture and Moxibustion Societies (WFAS) standard Practice Guideline of Acupuncture and Moxibustion for Urinary Incontinence in Women as an example, this paper focused on the specific process and results of three rounds of Delphi survey on clinical issues by experts of the guideline development group, and systematically analyzed the consistency of the modified Delphi method with the consensus of acupuncture and moxibustion experts, as well as the reflection and limitation of this consensus process, hoping to provide reference for the development of acupuncture guidelines in the same field.

[Acupoint selection rules of acupuncture and moxibustion for stroke-related pneumonia].

Using data mining technology, the rules of acupoint selection of acupuncture and moxibustion were explored in treatment of stroke-related pneumonia. The clinical articles of acupuncture and moxibustion in treatment of stroke-related pneumonia were retrieved from CNKI, SinoMed, Wanfang and VIP databases from their inception through to January l 2021, and then, the acupuncture-moxibustion prescription database was set up for stroke-related pneumonia. SPSS Modeler 18.0 Apriori algorithm was adopted to analyze the association rules of acupoints and draw complex network diagrams. SPSS26.0 was used in clustering analysis of acupoints. Finally, a total of 44 articles were included, with 51 acupoint prescriptions and 82 acupoints extracted. The total frequency of acupoints was 340 times. The high-frequency acupoints in treatment with acupuncture and moxibustion for stroke-related pneumonia were Feishu (BL 13), Fenglong (ST 40), Hegu (LI 4), etc. These acupoints were mainly distributed on the limbs and back and mostly from yang meridians. Of these extracted acupoints, the five-shu points, convergent points and back-shu points were selected specially. Regarding acupoint combination, the association of Quchi (LI 11) had the highest support with Hegu (LI 4) and Zusanli (ST 36). The core prescription of acupuncture-moxibustion treatment for stroke-related pneumonia could be composed of Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36), Fenglong (ST 40) and Taichong (LR 3).

[Consideration on the construction of acupuncture and moxibustion clinical diagnosis and treatment system with the core of "differentiation of disease location": taking "treatment" of Science of Acupuncture and Moxibustion as an example].

Based on the difference between disease and syndrome differentiation of acupuncture and moxibustion and each department of TCM, i.e. internal medicine, external medicine, gynecology and pediatrics, it is believed that "differentiation of disease location" is the key of disease and syndrome differentiation of acupuncture and moxibustion. According to the disease location, in the section "treatment" of Science of Acupuncture and Moxibustion, the disorders/illness are classified as zangfu disorder, disorders of limbs and meridians, dermatological disorder, ophthalmological and otorhinolaryngological disorder, gynecological disorder, as well as qi, blood and body fluid disorder. Besides, the rules of disease and syndrome differentiation, as well as treatment characteristics of each category are explained separately. It is considered that the clinical diagnosis and treatment system of acupuncture and moxibustion should be constructed by focusing on "differentiation of disease location".

[Study on positive reaction of foot three yin-meridians in patients with typeâ ¢ chronic prostatitis based on meridian diagnosis].

OBJECTIVE: To explore the relationship between typeⅢ chronic prostatitis and the positive reaction of foot three yin-meridians based on meridian diagnosis. METHODS: Using the traditional meridian diagnosis combined with tenderness meter detection, the positive reaction rate of meridians and acupoints of crural foot three yin-meridians and tenderness pain threshold of standard acupoint location were compared in the typeⅢ chronic prostatitis patients (prostatitis group, 32 cases) and healthy subjects (health group, 30 cases). RESULTS: The positive reaction rate of the spleen meridian was higher than those in the kidney meridian and the liver meridian in the prostatitis group (P<0.001). The positive reaction rates of the spleen meridian, the kidney meridian and the liver meridian and the total positive reaction rate of foot three yin-meridians in the prostatitis group were higher than those in the health group (P<0.001). In the prostatitis group, the positive reaction rates of Sanyinjiao (SP 6), Yinlingquan (SP 9), Taixi (KI 3), Ligou (LR 5), Diji (SP 8), Ququan (LR 8), Shangqiu (SP 5) and Zhongfeng (LR 4) were higher than those in the health group (P<0.001), the tenderness pain threshold of acupoints of crural foot three yin-meridians was lower than the health group (P<0.001). The positive reaction rate of the spleen meridian was positively correlated with the pain score and the total score of National Institute of Health chronic prostatitis symptom index (NIH-CPSI), and the positive reaction rate of the kidney meridian was positively correlated with age and international prostate symptom score (IPSS) in the prostatitis group. CONCLUSION: The positive reactions of foot three yin-meridians, especially the spleen meridian, are closely related to the pathological state of typeⅢ chronic prostatitis, pain and urination symptom are significantly correlated with the spleen meridian and the kidney meridian respectively.

[Analysis on specific effect of acupoints at the upper arms in treatment of scrofula and goiter].

Through analyzing the indication distribution of the different acupoints located at the upper limbs recorded in Science of Acupoints and Science of Meridians and Acupoints, the industry planning teaching materials of traditional Chinese medicine, it is discovered that the acupoints located at the upper arms are commonly selected for the treatment of scrofula and goiter, while the acupoints below the elbow at the hand meridians and those at the lower limbs of the foot meridians which running through the neck, do not have the similar indications. Based on a further analysis on the literature at ancient and modern times, it is believed that the acupoints located on the lateral side of the upper arms, especially those at the large intestine meridian of hand-yangming perhaps have the specific effect in treatment of scrofula and goiter.

[Quchi (LI 11) for treatment of allergic diseases based on coincidence of key therapeutic characteristics of acupoints and pathogenesis of allergic diseases].

According to the etiology, allergic diseases are related to wind and heat; according to the pathogenesis, most of allergic diseases are qi-blood diseases; from the theory of zangfu, allergic diseases are closely related to the depressed heat of yangming and stomach-intestine, and the common elements of the pathogenesis of allergic diseases are wind, heat, qi, blood and yangming. With reviewing the ancient literature and modern research, the key therapeutic effect of Quchi (LI 11) and its special treatment effect on allergic diseases are summarized. It is suggested that the key therapeutic characteristics of Quchi (LI 11), including dispelling the wind, clearing the heat, cooling the blood and regulating stomach-intestine function, are in accordance with the common causes and pathogenesis of allergic diseases. Therefore, Quchi (LI 11) is considered an important acupoint for the treatment of allergic diseases.

Acupuncture for Hashimoto thyroiditis: study protocol for a randomized controlled trial.

BACKGROUND: The incidence rate of Hashimoto thyroiditis (HT) has gradually increased in recent years. There has been no specific etiological treatment for HT. Even though with normal level of thyroid hormone, the patients may still suffer from various clinical symptoms, such as anterior neck discomfort, fatigue, and mood swings, which seriously impair their quality of life. Acupuncture has long been used in the treatment of thyroid diseases, but there has been no related standardized clinical study as of today. This study aims to assess the feasibility, efficacy, and safety of acupuncture for HT. METHODS: This is a randomized, black-controlled assessor-blinded pilot trial. A total of 60 patients will be recruited and divided into the experimental group (n = 30) or the control group (n = 30). The experimental group will undergo acupuncture therapy (penetration needling of Hand-Yangming meridian, PNHM) for 16 weeks, followed by a 16-week follow-up period, and the control group will first go through an observation period for 16 weeks, followed by a 16-week compensation PNHM therapy. The primary outcome will be the change of the concentrations of anti-thyroperoxidase antibodies (TPOAb), antithyroglobulin antibodies (TgAb), and thyroid hormone, including total thyroxine (FT4), free thyroxine (FT3), and thyroid-stimulating hormone (TSH). The secondary outcome measurements include the thyroid-related quality of life questionnaire short-form (ThyPRO-39), The Mos 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HAD). Data collection will be performed before the start of the study (the baseline assessment) and at weeks 8, 16, 24, and 32. DISCUSSION: The study is designed to assess the feasibility and effectiveness of PNHM in reducing the thyroid antibody level and improving the quality of life of HT patients with hypothyroidism or subclinical hypothyroidism. Results of this trial will assist further analyses on whether the acupuncture treatment can alleviate symptoms for patients with HT. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry AMCTR-IOR-19000308 ( ChiCTR1900026830 ). Registered on 23 October 2019.

The Underlying Mechanism of Paeonia lactiflora Pall. in Parkinson's Disease Based on a Network Pharmacology Approach.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, yet as of currently, there is no disease-modifying therapy that could delay its progression. Paeonia lactiflora Pall. is the most frequently used herb in formulas for PD in Traditional Chinese Medicine and also a potential neuroprotective agent for neurodegenerative diseases, while its mechanisms remain poorly understood. In this study, we aim to explore the underlying mechanism of P. lactiflora in treating PD utilizing a network pharmacology approach. Methods: The protein targets of P. lactiflora ingredients and PD were first obtained from several databases. To clarify the key targets, a Protein-Protein-Interaction (PPI) network was constructed and analyzed on the String database, and then enrichment analysis was performed by the Metascape platform to determine the main Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the Ingredient-Target-Pathway (I-T-P) network was constructed and analyzed by Cytoscape software. Results: Six active ingredients of P. lactiflora (kaempferol, ß-sitosterol, betulinic acid, palbinone, paeoniflorin and (+)-catechin) as well as six core targets strongly related to PD treatment [AKT1, interleukin-6, CAT, Tumor necrosis factor (TNF), CASP3, and PTGS2] were identified. The main pathways were shown to involve neuroactive ligand-receptor interaction, Calcium signaling pathway, PI3-Akt signaling pathway, TNF signaling pathway, and apoptosis signaling pathway. The main biological process included the regulation of neurotransmitter levels. Conclusion: P. lactiflora may retard neurodegeneration by reducing neuroinflammation, inhibiting intrinsic and extrinsic apoptosis, and may improve motor and non-motor symptoms by regulating the levels of neurotransmitters. Our study has revealed the mechanism of P. lactiflora in the treatment of PD and may contribute to novel drug development for PD.

The rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model

Dendritic cells (DCs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. The aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (LALNs) in the model of a non-human primate (NHP) infected by influenza A virus (IAV). Cynomolgus macaques were infected with influenza A virus (H3N2) via bronchoscopy. Flow cytometry was used to analyze the DC numbers, maturation status and subsets during the time of acute infection (days 1, 2, 3, 4, 7) and the resolution phase (day 30). A dramatic increase in the numbers of influenza A virus-infected CD11c+CD14- myeloid dendritic cells (mDCs) and CD11c-CD123+ plasmacytoid dendritic cells (pDCs) were observed from day 1 to day 4 and peak up from day 7 post-infection. In lung and lung-associated lymph nodes, the numbers and maturation status of myeloid dendritic cells and plasmacytoid dendritic cells increased more slowly than those in the lung tissues. On day 30 post-infection, influenza A virus challenge increased the number of myeloid dendritic cells, but not plasmacytoid dendritic cells, compared with baseline. These findings indicate that dendritic cells are susceptible to influenza A virus infection, with the likely purpose of increasing mature myeloid dendritic cells numbers in the lung and lung and lung-associated lymph nodes, which provides important new insights into the regulation of dendritic cells in a non-human primate model.

The rapid and sustained responses of dendritic cells to influenza virus infection in a non-human primate model.

Dendritic cells (DCs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. The aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (LALNs) in the model of a non-human primate (NHP) infected by influenza A virus (IAV). Cynomolgus macaques were infected with influenza A virus (H3N2) via bronchoscopy. Flow cytometry was used to analyze the DC numbers, maturation status and subsets during the time of acute infection (days 1, 2, 3, 4, 7) and the resolution phase (day 30). A dramatic increase in the numbers of influenza A virus-infected CD11c+CD14- myeloid dendritic cells (mDCs) and CD11c-CD123+ plasmacytoid dendritic cells (pDCs) were observed from day 1 to day 4 and peak up from day 7 post-infection. In lung and lung-associated lymph nodes, the numbers and maturation status of myeloid dendritic cells and plasmacytoid dendritic cells increased more slowly than those in the lung tissues. On day 30 post-infection, influenza A virus challenge increased the number of myeloid dendritic cells, but not plasmacytoid dendritic cells, compared with baseline. These findings indicate that dendritic cells are susceptible to influenza A virus infection, with the likely purpose of increasing mature myeloid dendritic cells numbers in the lung and lung and lung-associated lymph nodes, which provides important new insights into the regulation of dendritic cells in a non-human primate model.

IL-4 confers resistance to IL-27-mediated suppression on CD4+ T cells by impairing signal transducer and activator of transcription 1 signaling.

BACKGROUND: TH2 cells play a critical role in the pathogenesis of allergic asthma. Established TH2 cells have been shown to resist reprogramming into TH1 cells. The inherent stability of TH2 cells poses a significant barrier to treating allergic diseases. OBJECTIVE: We sought to understand the mechanisms by which CD4(+) T cells from asthmatic patients resist the IL-27-mediated inhibition. METHODS: We isolated and cultured CD4(+) T cells from both healthy subjects and allergic asthmatic patients to test whether IL-27 can inhibit IL-4 production by the cultured CD4(+) T cells using ELISA. Culturing conditions that resulted in resistance to IL-27 were determined by using both murine and human CD4(+) T-cell culture systems. Signal transducer and activator of transcription (STAT) 1 phosphorylation was analyzed by means of Western blotting and flow cytometry. Suppressor of cytokine signaling (Socs) mRNA expression was measured by using quantitative PCR. The small interfering RNA method was used to knockdown the expression of Socs3 mRNA. RESULTS: We demonstrated that CD4(+) T cells from asthmatic patients resisted the suppression of IL-4 production mediated by IL-27. We observed that repeated exposure to TH2-inducing conditions rendered healthy human CD4(+) T cells resistant to IL-27-mediated inhibition. Using an in vitro murine culture system, we further demonstrated that repeated or higher doses of IL-4 stimulation, but not IL-2 stimulation, upregulated Socs3 mRNA expression and impaired IL-27-induced STAT1 phosphorylation. The knockdown of Socs3 mRNA expression restored IL-27-induced STAT1 phosphorylation and IL-27-mediated inhibition of IL-4 production. CONCLUSIONS: Our findings demonstrate that differentiated TH2 cells can resist IL-27-induced reprogramming toward TH1 cells by downregulating STAT1 phosphorylation and likely explain why the CD4(+) T cells of asthmatic patients are resistant to IL-27-mediated inhibition.