Dynamic and fluctuating generation of hydrogen peroxide via photorespiratory metabolic channeling in plants.

The homeostasis of hydrogen peroxide (H2 O2 ), a key regulator of basic biological processes, is a result of the cooperation between its generation and scavenging. However, the mechanistic basis of this balance is not fully understood. We previously proposed that the interaction between glycolate oxidase (GLO) and catalase (CAT) may serve as a molecular switch that modulates H2 O2 levels in plants. In this study, we demonstrate that the GLO-CAT complex in plants exists in different states, which are dynamically interchangeable in response to various stimuli, typically salicylic acid (SA), at the whole-plant level. More crucially, changes in the state of the complex were found to be closely linked to peroxisomal H2 O2 fluctuations, which were independent of the membrane-associated NADPH oxidase. Furthermore, evidence suggested that H2 O2 channeling occurred even in vitro when GLO and CAT worked cooperatively. These results demonstrate that dynamic changes in H2 O2 levels are physically created via photorespiratory metabolic channeling in plants, and that such H2 O2 fluctuations may serve as signals that are mechanistically involved in the known functions of photorespiratory H2 O2 . In addition, our study also revealed a new way for SA to communicate with H2 O2 in plants.

Evaluating the Effects of Heat-Clearing Traditional Chinese Medicine in Stable Bronchiectasis by a Series of N-of-1 Trials.

PURPOSE: The purpose of this study is to study the effects of heat-clearing Traditional Chinese Medicine (TCM) in the stable stage of bronchiectasis via N-of-1 trials. METHODS: The N-of-1 trials in this study were randomized and double-blinded with crossover comparisons consisting of three pairs. Each pair was of two 4-week periods. Each patient took the individualized decoction in the experimental period and the individualized decoction was removed of heat-clearing drugs, mainly including heat-clearing and detoxifying drugs, in the control period for three weeks. After three weeks, the patients stopped taking the decoction for one week. The primary outcome was from patients' self-reporting symptoms scores on a 1-7-point Likert scale. Mixed-effects models were used to conduct statistical analysis on these N-of-1 trials. RESULTS: Of the 21 patients enrolled, 15 completed three pairs of N-of-1 trials (71.43%). (1) Seen from the individual level, no statistical difference between the experimental decoction and the control (P > 0.05) was observed. However, 5 patients found better decoctions according to the clinical criteria. (2) As revealed by the group data of all the N-of-1 trials, the control was better than the individualized decoction in terms of symptom scores on the Likert scale (1.94 ± 0.69 versus 2.08 ± 0.68, P = 0.04, mean difference, and 95% CI: 0.19 (0.01, 0.37)) and on CAT scores (13.66 ± 6.57 versus 13.95 ± 6.97, P = 0.04, mean difference, and 95% CI: 0.86 (0.042, 1.67)), but such differences were not clinically significant. The other outcomes, such as Likert scale score of respiratory symptoms and 24-hour sputum volume, showed no statistical difference. CONCLUSION: The experimental design of this study can make the TCM individualized treatment fully play its role and can detect the individualized tendencies according to the severity of phlegm and heat in some subjects. With the intermittent use or reduced use of heat-clearing drugs, most of the subjects, at the group level, enrolled in the series of N-of-1 trials may improve the symptoms and quality of life while saving the cost of TCM and reducing the potential side effects of heat-clearing TCM. This trial is registered with clinicaltrials.goc (NCT03147443).

Methodological Considerations in N-of-1 Trials of Traditional Chinese Medicine.

More and more scholars choose N-of-1 trials for TCM clinical research. However, the quality of the experimental designs was uneven. Accumulating more than eight years of experience in exploring the N-of-1 trials of TCM, the authors and their team searched the related literature in main Chinese and English databases, referenced to relevant Chinese and international guidelines. The design, implementation, and data analysis of N-of-1 trials of TCM are still in in-depth exploration and practice. "Carryover effect" may affect the design and quality of the trials. Individualized treatment should be guided by the classic theories of TCM. It is expected to formulate reasonable observation periods and pairs and closely integrate individual and group statistical analysis.

A Series of N-of-1 Trials for Traditional Chinese Medicine Using a Bayesian Method: Study Rationale and Protocol.

Background. Our previous studies showed that N-of-1 trials could reflect the individualized characteristics of traditional Chinese medicine (TCM) syndrome differentiation with good feasibility, but the sensitivity was low. Therefore, this study will use hierarchical Bayesian statistical method to improve the sensitivity and applicability of N-of-1 trials of TCM. Methods/Design. This is a randomized, double-blind, placebo-controlled, three-pair crossover trial for a single subject, including 4-8 weeks of run-in period and 24 weeks of formal trial. In this study, we will recruit a total of 30 participants who are in the stable stage of bronchiectasis. The trial will be divided into three pairs (cycles), and one cycle contains two observation periods. The medications will be taken for three weeks and stopped for one week in the last week of each observation period. The order of syndrome differentiation decoction and placebo will be randomly determined. Patient self-reported symptom score (on a 7-point Likert scale) is the primary outcome. Discussion. Some confounding variables (such as TCM syndrome type and potential carryover effect of TCM) will be introduced into hierarchical Bayesian statistical method to improve the sensitivity and applicability of N-of-1 trials of TCM, and the use of prior available information (e.g., "borrowing from strength" of previous trial results) within the analysis may improve the sensitivity of the results of a series of N-of-1 trials, from both the individual and population level to study the efficacy of TCM syndrome differentiation. It is the exploration of improving the objective evaluation method of the clinical efficacy of TCM and may provide reference value for clinical trials of TCM in other chronic diseases. This trial is registered with ClinicalTrials.gov (ID: NCT04601792).

Investigation into the Individualized Treatment of Traditional Chinese Medicine through a Series of N-of-1 Trials.

PURPOSE: To compare the efficacy of individualized herbal decoction with standard decoction for patients with stable bronchiectasis through N-of-1 trials. METHODS: We conducted a single center N-of-1 trials in 17 patients with stable bronchiectasis. Each N-of-1 trial contains three cycles. Each cycle is divided into two 4-week intervention including individualized decoction and fixed decoction (control). The primary outcome was patient self-reported symptoms scores on a 1-7 point Likert scale. Secondary outcomes were 24-hour sputum volume and CAT scores. RESULTS: Among 14 completed trials, five showed that the individualized decoction was statistically better than the control decoction on symptom scores (P < 0.05) but was not clinically significant. The group data of all the trials showed that individualized decoction was superior to control decoction on symptom scores (2.13 ± 0.58 versus 2.30 ± 0.65, P = 0.002, mean difference and 95% CI: 0.18 (0.10, 0.25)), 24 h sputum volume (P = 0.009), and CAT scores (9.69 ± 4.89 versus 11.64 ± 5.59, P = 0.013, mean difference and 95% CI: 1.95 (1.04, 2.86)) but not clinically significant. CONCLUSION: Optimizing the combined analysis of individual and group data and the improvement of statistical models may make contribution in establishing a method of evaluating clinical efficacy in line with the characteristics of traditional Chinese medicine individual diagnosis and treatment.

Evaluating the Individualized Treatment of Traditional Chinese Medicine: A Pilot Study of N-of-1 Trials.

Purpose. To compare the efficacy of individualized herbal decoction with controlled decoction for individual patients with stable bronchiectasis. Methods. We conducted N-of-1 RCTs (single-patient, double-blind, randomized, multiple crossover design) in 3 patients with stable bronchiectasis. The primary outcome was patient self-rated symptom scores on visual analogue scales. Secondary outcome was 24-hour sputum volume. A clinical efficacy criterion which combined symptoms score and medication preference was also formulated. Results. All three patients showed various degrees of improvement on their symptoms and one patient's (Case 3) 24 h sputum volume decreased from 70 mL to 30 mL. However, no significant differences were found between individualized herbal decoction and control decoction on symptoms score, or on 24-hour sputum volume. One patient (Case 2) had clear preference for the individualized herbal decoction over the standard one with the confirmation after unblinding. We therefore considered this case as clinically important. Discussion. N-of-1 trials comply with individualized philosophy of TCM clinical practice and had good compliance. It is necessary to set up clinical efficacy criteria and to consider the interference of acute exacerbation.

[Efficacy observation of chronic obstructive pulmonary disease due to lung and kidney deficiency treated with acupoint-catgut-embedding therapy combined western medication].

OBJECTIVE: To observe the clinical efficacy of acupoint-catgut-embedding therapy combined conventional western medication on chronic obstructive pulmonary disease (COPD) at stable stage due to lung and kidney deficiency. METHODS: The cases were randomized into observation group and control group, 30 cases in each one. In control group, the conventional western medication was administered. In observation group, on the basis of conventional western medication, the catgut-embedding therapy was applied at Dingchuan (EX-B 1), Feishu (BL 13), Shenshu (BL 23), Fenglong (ST 40) and Zusanli (ST 36). The total attack frequency of acute exacerbation of COPD (AECOPD), the attack frequency of AECOPD at moderate or above moderate stage and TCM syndrome score were compared before treatment and 6 months after treatment in two groups. RESULTS: The total effective rate was 93.3% (28/30) in observation group and was 90.0% (27/30) in control group, indicating equivalent efficacy between two groups. 6 months after treatment, in two groups, the total attack frequency of AECOPD and the attack frequency of AECOPD at moderate or above moderate stage were reduced remarkably as compared with those before treatment (P < 0.01, P < 0.05). The total attack frequency of AECOPD in observation group was reduced remarkably as compared with that in control group (P < 0.05). The scores of cough, expectoration and chest oppression as well as the total score of TCM syndrome were reduced remarkably after treatment in observation group (all P < 0.01). CONCLUSION: Integrated therapy of acupoint-catgut-embedding and conventional medication has similar efficacy as simple medication. But, the combination of acupoint-catgut-embedding therapy and western medication can reduce the attack frequency of AECOPD and improve in cough, chest oppression and other symptoms in patients with COPD at stable stage effectively.

[Prognostic analysis of advanced non small cell lung cancer treated by sequential chemo-radiation therapy combined with traditional Chinese medicine: a report of 54 cases].

OBJECTIVE: To evaluate the influence of fewer courses and prolonged intervals of chemotherapy on survival rate of advanced non small cell lung cancer (NSCLC) patients treated by sequential chemo-radiation therapy combined with traditional Chinese medicine (TCM). METHODS: From Jan. 2000 to Dec. 2001, 54 untreated advanced NSCLC patients (2 stage IIIa, 18 stage IIIb, 34 stage IV) were treated by sequential chemo-radiation therapy combined with TCM. The courses of chemotherapy were reduced and the intervals of chemotherapy were longer than that of the standard regimen. The efficacy and survival rate were documented and the prognostic factors were analyzed. RESULTS: Complete remission (CR) was observed in 1 case and partial remission (PR) in 20 cases. The overall objective response rate was 40.4%. Median survival was 15.3 months, 1-, 2- and 3-year survival rate were 53.7%, 28.9% and 9.6% respectively. The median survival of stage III and IV were 21.8 months and 12.5 months respectively. The 1-, 2-, and 3-year survival rates of stage III were 65.0%, 49.5%, 24.7% and that of stage IV were 47.0%, 23.3%, 0%, respectively. The quality of life was improved in most of the patients. Cox's proportional hazards regression showed that improved quality of life and treatment of TCM were the significant prognostic factors of overall survival. CONCLUSION: Chemotherapy and radiotherapy combined with TCM is beneficial to extending the interval of chemotherapy, improving the quality of life, and increasing the survival rate of advanced NSCLC patients.