Characterization of unique pattern of immune cell profile in patients with nasopharyngeal carcinoma through flow cytometry and machine learning.

In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell profile for patients with NPC and used flow cytometry and machine learning (ML) to identify the characteristics of this profile. After isolation of circulating leukocytes, the proportions of 104 immune cell subsets were compared between NPC group and the healthy control group (HC). Data obtained from the immune cell profile were subjected to ML training to differentiate between the immune cell profiles of the NPC and HC groups. We observed that subjects in the NPC group presented higher proportions of T cells, memory B cells, short-lived plasma cells, IgG-positive B cells, regulatory T cells, MHC II+ T cells, CTLA4+ T cells and PD-1+ T cells than subjects in the HC group, indicating weaker and compromised cellular and humoral immune responses. ML revealed that monocytes, PD-1+ CD4 T cells, memory B cells, CTLA4+ CD4 Treg cells and PD-1+ CD8 T cells were strongly contributed to the difference in immune cell profiles between the NPC and HC groups. This alteration can be fundamental in developing novel immunotherapies for NPC.

Integrative traditional Chinese medicine treatment for children with obstructive sleep apnea.

Purpose: Obstructive sleep apnea (OSA) is a chronic disease that affects 1%-6% of children. Our study aims to explore the effectiveness and clinical characteristics of integrative Traditional Chinese Medicine (ITCM) for pediatric OSA. Materials and methods: In this retrospective cohort study, we assessed differences of polysomnography (PSG) parameters and clinical characteristics between 2009 and 2020. Children <12 years old diagnosed with OSA (n = 508) were included and were categorized into ITCM cohort, western medicine (WM) cohort ,and surgery cohort. Outcomes were apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and body mass index (BMI). Results: There were 56 (11%), 324 (63.8%), and 128 (25.2%) patients in the ITCM, WM, and surgery cohorts. Among 17, 26, and 33 patients in the ITCM, WM, and surgery cohorts underwent follow-up PSG studies, respectively. In the ITCM follow-up cohort, AHI were significantly reduced (9.59 to 5.71, p < 0.05). BMI significantly increased in the WM follow-up cohort (19.46 to 20.50, p < 0.05) and the surgery follow-up cohort (18.04 to 18.85, p < 0.01). Comparing ITCM to WM cohort, a significant difference was found between the changes in RDI (ITCM: -6.78, WM: 0.51, p < 0.05) after treatment. Among ITCM follow-up cohort, the most prescribed TCM formula was Forsythia and Laminaria Combination. The most prescribed TCM herb was Ephedrae Herba. Conclusions: ITCM therapy can significantly reduce RDI and control BMI. We identified potential TCM treatments for pediatric OSA. Further study of the pharmacological mechanisms and clinical efficacy is warranted.

Artificial intelligence-based immunoprofiling serves as a potentially predictive biomarker of nivolumab treatment for advanced hepatocellular carcinoma.

Immune checkpoint inhibitors (ICI) have been applied in treating advanced hepatocellular carcinoma (aHCC) patients, but few patients exhibit stable and lasting responses. Moreover, identifying aHCC patients suitable for ICI treatment is still challenged. This study aimed to evaluate whether dissecting peripheral immune cell subsets by Mann-Whitney U test and artificial intelligence (AI) algorithms could serve as predictive biomarkers of nivolumab treatment for aHCC. Disease control group carried significantly increased percentages of PD-L1+ monocytes, PD-L1+ CD8 T cells, PD-L1+ CD8 NKT cells, and decreased percentages of PD-L1+ CD8 NKT cells via Mann-Whitney U test. By recursive feature elimination method, five featured subsets (CD4 NKTreg, PD-1+ CD8 T cells, PD-1+ CD8 NKT cells, PD-L1+ CD8 T cells and PD-L1+ monocytes) were selected for AI training. The featured subsets were highly overlapping with ones identified via Mann-Whitney U test. Trained AI algorithms committed valuable AUC from 0.8417 to 0.875 to significantly separate disease control group from disease progression group, and SHAP value ranking also revealed PD-L1+ monocytes and PD-L1+ CD8 T cells exclusively and significantly contributed to this discrimination. In summary, the current study demonstrated that integrally analyzing immune cell profiling with AI algorithms could serve as predictive biomarkers of ICI treatment.

The Effects of Laser Acupuncture Therapy on Nocturnal Enuresis: A Systematic Review and Meta-Analysis.

Introduction: Nocturnal enuresis (NE), often known as bedwetting, is a common condition in children and, as a result, they may have subsequent social impairments. The aim of this study was to evaluate the efficacy of low-level laser therapy (LLLT) in children with NE. Methods: International databases with laser- and NE-related keywords were searched, and only randomized controlled trials (RCTs) that used any type of LLLT to treat NE and compared it with any type of control intervention were included. Eleven studies using laser acupuncture therapy (LAT), involving 927 participants, were included for a systematic review. A meta-analysis was conducted using full and partial response-rate variables. The analysis was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and the Cochrane risk-of-bias tool and Grading of Recommendations Assessment Development and Evaluation recommendations for quality of evidence were used to rate all included publications. Results: The LAT groups showed significant improvement, compared with control groups when full response rates were analyzed. There was no significant difference between the groups treated with LAT and the groups who underwent medication therapy alone when full response rates were analyzed. Red and infrared wavelengths and continuous waves were the most commonly used LAT modalities, and lower abdomen and back acupoints were the most-common sites. Conclusions: LAT seems to be an effective and safe treatment for NE; however, the quality of evidence available in the literature was relatively low. More-rigorous and higher-quality trials are needed to investigate this treatment modality further.

Validation of the traditional Chinese version of the Sinus and Nasal Quality of Life Survey (SN-5) for children.

BACKGROUND: Persistent sinonasal symptoms are common in children with chronic rhinosinusitis. The Sinus and Nasal Quality of Life (QoL) Survey (SN-5) was the first validated questionnaire measuring sinonasal-related QoL in populations aged 2-12 years. No norm has been established for Chinese-speaking countries. We translated the SN-5 into traditional Chinese and evaluated validity and reliability. METHODS: From December 2016 to December 2017, healthy volunteers and children with persistent sinonasal symptoms were enrolled. Guardians of the participants completed the SN-5, a visual analog scale (VAS) of nasal symptoms, and the Obstructive Sleep Apnea-18 (OSA-18); the responses were used to assess internal consistency, discriminant validity, and treatment responsiveness. A nontreatment group was administered the SN-5 1 week later to assess test-retest reliability. RESULTS: We recruited 31 healthy volunteers and 85 children with rhinosinusitis, 50 and 35 in the treatment and nontreatment groups, respectively. The SN-5 demonstrated good internal consistency (Cronbach's α = 0.86) and test-retest reliability (0.74, p < 0.01). It exhibited good discriminant validity between the healthy and rhinosinusitis groups (p < 0.001). The SN-5 scores were correlated with the VAS scores (0.63, p < 0.001). The effect size of the SN-5 scores was 0.51. The total SN-5 and OSA-18 scores changed significantly after 4-week treatment (p < 0.05) and demonstrated good responsiveness. The SN-5 and OSA-18 scores were significantly and positively correlated (r2 = 0.53, p < 0.001). CONCLUSION: Our traditional Chinese version of the SN-5 is reliable and valid for measuring sinonasal-related QoL in children in Chinese-speaking countries. TRIAL REGISTRATION NUMBER: NCT04836403.

Allergic rhinitis and dental-supporting tissue diseases in children.

ABSTRACT: The etiology of dental-supporting tissue diseases in children is multi factorial and not merely related to oral hygiene. Therefore, in the present study, we investigated the relationship between children <18 years old with allergic rhinitis (AR) and the risk of dental-supporting tissue diseases.Data from the National Health Insurance Research Database (NHIRD) of Taiwan were used to conduct a retrospective longitudinal cohort study. The study cohort comprised 378,160 patients with AR (AR group) and 378,160 patients without AR (non-AR group), who were selected through frequency matching based on age, sex, and the index year. The study patients were followed until dental-supporting tissue diseases occurrence, withdrawal from the National Health Insurance program, or December 31, 2013. Cox proportional hazards regression analysis was conducted to calculate the risk of dental-supporting tissue diseases in the AR group after adjustment for age, sex, and relative comorbidities.The adjusted HRs of periodontal, pulp, and periapical diseases in AR children were higher than those in the non-AR controls (1.51, 95% CI: 1.50 to 1.53; 1.06, 95% CI: 1.05 to 1.07, respectively). The AR to non-AR HRs of these inflammatory dental diseases were particularly higher in children <6 years old and in boys. The HRs of periodontal, pulp, and periapical diseases were greatest in those with >5 AR-related medical visits/year (5.57, 95% CI: 5.50 to 5.56; 4.06, 95% CI: 4.00 to 4.12, respectively).Children with AR had a greater risk of inflammatory dental-supporting tissue diseases, particularly those <6 years old with primary teeth, boys, and those with severe persistent AR.

Allergic rhinitis and the associated risk of nocturnal enuresis in children: a population-based cohort study.

BACKGROUND: Despite controversy, an association between allergy and nocturnal enuresis (NE) has been reported for almost a century. Allergic rhinitis (AR)-associated sleep-disordered breathing frequently results in microarousals during sleep, decreased sleep efficiency, and change in sleep pattern and behavior. NE is a common sleep disorder in children. Hence, this study aimed to investigate the incidence and risk of NE in children with AR. METHODS: A population-based cohort study was conducted among 327,928 children with AR and 327,601 non-AR controls between 2000 and 2012 in Taiwan. By the end of 2012, the incidence of NE in both cohorts, and the AR-to-non-AR cohort hazard ratios (HRs) were measured. RESULTS: The adjusted HR of NE during the study period was 1.7-fold higher in the AR cohort compared to the non-AR cohort. The risk was greater for boys, children younger than 6 years old, those with comorbidities of asthma, atopic dermatitis, and attention deficit/hyperactivity disorder (ADHD), and those who had more than 5 AR-related medical visits per year. The risk of NE in the AR cohort decreased with follow-up time and was the highest within the first year after AR diagnosis. CONCLUSION: Children with AR had a higher incidence and subsequent risk of NE. The risk of NE was greater for boys, younger children, and those with more frequent health utilization for AR symptoms.

Characteristics of Traditional Chinese Medicine Use in Pediatric Cancer Patients: A Nationwide, Retrospective, Taiwanese-Registry, Population-Based Study.

BACKGROUND: Large-scale surveys of complementary traditional Chinese medicine (TCM) use in pediatric cancer patients are lacking. The aim of our study was to investigate the use of TCM in pediatric cancer patients. METHODS: We analyzed cancer patients younger than 18 years (n = 12 965) who were registered in the National Health Insurance Research Database in Taiwan between 2001 and 2011. Patients were categorized into TCM or non-TCM users based on their use of TCM. RESULTS: In Taiwan, 8086 (62.4%) children with cancer sought TCM treatment at some point. Children in older age groups, including school-aged children and adolescents, were more likely to use TCM. There was no significant difference in the distributions of gender and urbanization. The 3 most common diseases for which TCM users visited the clinic were neoplasm (33.2%), respiratory system disease (32.9%), and infectious disease (8.86%). The most commonly utilized TCM therapy was Chinese herbal remedies. Patients who had comorbid conditions such as allergic rhinitis, dyspepsia, disorders of menstruation, and disease of the musculoskeletal system and connective tissue tended to visit TCM clinics. CONCLUSIONS: Adjunctive TCM use is not low in Taiwanese children with cancer. Further studies to investigate the efficacy and safety of TCM in children with cancer are warranted.

ECMO Used in a Refractory Ventricular Tachycardia and Ventricular Fibrillation Patient: A National Case-Control Study.

Refractory cardiac arrhythmia, which has a poor response to defibrillation and antiarrhythmia medication, is a complicated problem for clinical physicians during resuscitation. Extracorporeal membrane oxygenation (ECMO) may be used to sustain life in this situation. ECMO is useful for cardiopulmonary resuscitation among patients suffering from cardiac arrest; the use of ECMO in this context is called E-cardiopulmonary resuscitation. However, a large-scale and nationwide survey of ECMO usage in cases involving refractory cardiac arrhythmia during resuscitation is lacking. We aimed to clarify the characteristics and efficacy of the application of ECMO in cases involving refractory cardiac arrhythmia during resuscitation by conducting a nationwide study. Using national insurance data from 1996 to 2011, 2702 patients who received defibrillation and amiodarone injections were selected. We excluded trauma patients (n = 316) and those aged<20 years (n = 24). A total of 2362 patients were included, 376 of whom had ECMO support, and 1986 of whom had no ECMO support. After propensity score matching, 320 patients had ECMO support and 640 patients without ECMO support. Conditional logistic regression was used to estimate the risk of death in ECMO users compared to non-EMCO users. ECMO used in refractory cardiac arrhythmia with high propensity score patients had lower risk of death (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.36-0.98). However, prolonged ECMO used >1 day was higher risk of death (OR = 2.88, 95% CI = 1.27-6.53). In our retrospective case control study in refractory cardiac arrhythmia patients, ECMO supportive in high propensity score patients showed improving the overall survival rate but ECMO support for >1 day would be harmful. The evidence derived from this retrospective study using data from the national insurance system is generally of lower methodological evidence than that from randomized controlled trials because a retrospective study is subject to many biases due to lack of the necessary adjustments for possible confounding factors. Therefore, further investigation with a randomized clinical trial is needed to recommend ECMO as a routine in this specific population of patients experiencing cardiac arrest and refractory VT and VF.

Prescription patterns of traditional Chinese medicine for peptic ulcer disease in Taiwan: A nationwide population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer disease is a common digestive disease. There is a lack of large-scale survey on the use of traditional Chinese medicine (TCM) for the treatment of peptic ulcer disease. This study aimed to investigate the utilization of TCM for the treatment of peptic ulcer disease in Taiwan. MATERIALS AND METHODS: We analyzed a random sample comprised of one million individuals with newly diagnosed peptic ulcer disease between 2001 and 2010 from the National Health Insurance Research Database in Taiwan. Demographic characteristics and TCM usage, including Chinese herbal formulas and the single herbs prescribed for patients with peptic ulcer disease, were analyzed. RESULTS: A total of 96,624 newly diagnosed subjects with peptic ulcer disease were included. 14,983 (15.5%) patients were TCM users. People residing in highly urbanized areas, younger people and female (compared with male) were more likely to use TCM. With regard to the comorbidities, TCM users had a lower prevalence of coronary artery disease, chronic obstructive lung disease, diabetes mellitus and liver cirrhosis and stroke. The average time between onset of peptic ulcer disease and the first visit to a TCM clinic was 4.7 months. Majority of the patients (n=14,449; 96.4%) received only Chinese herbal remedies. The most frequently prescribed Chinese herbal formula and single herb was Ban-Xia-Xie-Xin-Tang (Pinelliae Decoction to Drain the Epigastrium) and Hai-Piao-Xiao (Os Sepiae), respectively. The core pattern analysis showed that combination of Ban-Xia-Xie-Xin-Tang, Hai-Piao-Xiao (Os Sepiae), Yan-Hu-Suo (Rhizoma Corydalis), Bei-Mu (Bulbus Fritillariae Thunbergii) and Chuan-Lian-Zi (Fructus Toosendan) was most frequently used for peptic ulcer disease. CONCLUSIONS: Our study identified the core prescription patterns of TCM for patients with peptic ulcer disease in Taiwan. Further basic and clinical studies are necessary to elucidate the efficacy and mechanisms.