Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol.

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

[Priority ranking of Chinese patent medicine prescriptions for type 2 diabetes mellitus (syndrome of deficiency of both Qi and Yin): based on analytic hierarchy process (AHP)].

Clinical expertise, patient preference, and the best evidence are the three elements of evidence-based medicine. Based on high-level and high-quality evidence, qualitative and quantitative analysis of the prescribing decisions of physicians is beneficial to improving clinical efficacy. A mature methodological system is available for the retrieval, analysis, summary, evaluation, and recommendation of the evidence, but there are still few studies on physicians' prescribing decisions. How to analyze the trend of physicians' prescribing decisions based on the priority ranking in addition and subtraction of prescriptions? Analytic hierarchy process(AHP) is a method for decision making, which arranges the elements of the decision problem into overall goal, criteria, and operational sub-criteria, and uses the matrix eigenvector method to solve the problem. This study aims to analyze the priority of physicians' prescribing decisions for diabetes mellitus with deficiency of both Qi and Yin based on AHP. To be specific, a database of diabetes mellitus cases with deficiency of both Qi and Yin was established and AHP was used to yield the priority ranking of Chinese patent medicine prescriptions in specific clinical scenarios. In the selected cases of diabetes mellitus with deficiency of both Qi and Yin, Xiaoke Pills was the best prescription for the treatment of type 2 diabetes mellitus(deficiency of both Qi and Yin)(normalized=0.388), followed by Liuwei Dihuang Pills(normalized=0.269), Qishen Capsules(normalized=0.230), and Shengmai Injection(normalized=0.113). According to the analysis the available data, for type 2 diabetes mellitus(deficiency of both Qi and Yin), Xiaoke Pills was the most effective prescription in specific scenarios. When the physicians' prescribing decisions are consistent with the evidence, quantitative analysis of physicians' cognition will boost the evidence-based medical decision-making. However, the research results are also affected by the quality of literature, evidence level and priority, which are thus have some limitations. It is recommended that further small data research based on individual cases be carried out to lay a evidence-based basis for the clinical decision-making of type 2 diabetes mellitus.

A metabolomic approach to elucidate the inhibitory effects of baicalin in pulmonary fibrosis.

CONTEXT: Baicalin, a major flavonoid extracted from Scutellaria baicalensis Georgi (Lamiaceae), has been shown to exert therapeutic effects on pulmonary fibrosis (PF). OBJECTIVE: To use serum metabolomics combined with biochemical and histopathological analyses to clarify anti-PF mechanisms of baicalin on metabolic pathways and the levels of potential biomarkers. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were randomly divided into the control, PF model, prednisolone acetate-treated (4.2 mg/kg/day) and baicalin-treated (25 and 100 mg/kg/day) groups. A rat model of PF was established using a tracheal injection of bleomycin, and the respective drugs were administered intragastrically for 4 weeks. Histomorphology of lung tissue was examined after H&E and Masson's trichrome staining. Biochemical indicators including SOD, MDA and HYP were measured. Serum-metabonomic analysis based on UPLC-Q-TOF/MS was used to clarify the changes in potential biomarkers among different groups of PF rats. RESULTS: Both doses of baicalin effectively alleviated bleomycin-induced pathological changes, and increased the levels of SOD (from 69.48 to 99.50 and 112.30, respectively), reduced the levels of MDA (from 10.91 to 5.0 and 7.53, respectively) and HYP (from 0.63 to 0.41 and 0.49, respectively). Forty-eight potential biomarkers associated with PF were identified. Meanwhile, the metabolic profiles and fluctuating metabolite levels were normalized or partially reversed after baicalin treatment. Furthermore, baicalin was found to improve PF potentially by the regulation of four key biomarkers involving taurine and hypotaurine metabolism, glutathione metabolism, and glycerophospholipid metabolism. CONCLUSIONS: These findings revealed the anti-fibrotic mechanisms of baicalin and it may be considered as an effective therapy for PF.

Acupuncture for the Treatment of Oculomotor Paralysis: A Pilot Randomised Controlled Trial.

This study consisted of a single centre randomised controlled trial with two parallel arms: an acupuncture group (n = 20) with 27 affected eyes and a sham group (n = 20) with 23 affected eyes. Participants in the acupuncture group received acupuncture treatment once daily, three times weekly for four weeks. Participants assigned to the control group received sham acupuncture, the same protocol as that used for the acupuncture group but without insertion of needles into the skin. The primary outcome measure was the cervical range of motion (CROM) score. Secondary outcome measures were the palpebral fissure size, response rate, and adverse events. All 40 participants completed the study. In the comparison of acupuncture and sham acupuncture, a significant difference was observed between acupuncture and sham acupuncture in CROM score (21.37 ± 15.16 and 32.21 ± 19.54, resp.) (P < 0.05) and palpebral fissure size (7.19 ± 2.94 and 5.41 ± 2.45, resp.) (P < 0.05). Response rate was also significantly different in the acupuncture group (P < 0.05). No adverse events were reported in both groups in this study. In summary, it was demonstrated that acupuncture had a feasibility positive effect on oculomotor paralysis.

[A multi-centered randomized double-blinded controlled clinical study on efficacy of gulling pa'an capsule in treating Parkinson's disease].

OBJECTIVE: To objectively evaluate the clinical efficacy of Gulling Pa'an Capsule (GPC), a Chinese medicine, in treating Parkinson's disease (PD). METHODS: According to the good clinical practice (GCP) principle, a multi-centered, double-blinded, layered, randomized and grouping-controlled clinical trial was carried out from May 2002 to January 2005 on 242 PD patients. Among them, 53 patients who had never received levodopa were randomized into two groups, 28 in group A treated with GPC, and 25 in group B treated with placebo; patients who had received levodopa were assigned depending on the Hoehn & Yahr (H-Y) grade, to 4 groups, 75 and 19 of grade 1.5 -3 in group C and E, respectively, 79 and 16 of grade 4 in group D and F, respectively, patients in group C and E were treated with GPC and Levodopa, and those in group D and F treated with placebo and Levodopa for control. The treatment course was 12 weeks for all. Changes of unified Parkinson's disease rating scale (UPDRS) II/III scores in comparing with the baseline were assessed. For the groups C, D, E and F, the dosage of levodopa administered was also recorded. Meanwhile, the blood pressure, pulse rate, blood and urine routine, liver and renal functions, electrocardiogram (ECG) and adverse reactions were monitored as the indices for safety supervise. RESULTS: (1) After treatment, symptoms were markedly improved in 1 out of the 28 patients in group A and improved in 11, the markedly improving rate was 3.6% and the improving rate 39.3%; while in group B, the corresponding outcomes were 0 (0/25) and 28.0% (7/25) respectively, showing insignificant difference between the two groups. UPDRS scores, including the total, II and III scores were all significantly lowered in group A after treatment (P < 0.01, P < 0.05); while in group B, significant lowering only showed in terms of UPDRS III (P < 0.05); but the inter-group comparison of the changes in all the three items showed no significant difference. (2) The significant improving rate was 12.0% (9/75) and improving rate 48.0% (36/75) in group C, while those in group D, 12.7% (10/79) and 24.1% (19/79) respectively, the efficacy in group C was better (P < 0.05). The items of 3 UPDRS scores in groups C and D were all significantly lowered after treatment (P < 0.01), and the lowering in group C was more significant in terms of the total and II scores (P < 0.05). (3) The significant improving rate was 5.3% (1/19) and improving rate 36.8% (7/19) in group E, while in group F 0% (0/19) and 25.0% (4/16), respectively, showing insignificant difference between them; UPDRS scores lowered significantly in the two groups after treatment (P < 0.01), also showed no statistical significance in comparison (P > 0.05). (4) The dosage of Levodopa required in groups C and E was significantly reduced after treatment (P < 0.05), while in groups D and F, it was unchanged (P > 0.05); yet, the further analysis displayed that significant reduction only presented in group C (P < 0.05), not in the other three groups. CONCLUSIONS: The overall efficacy of levodopa in combined with GPC for treating PD patients of H-Y grade 1.5 -3 is significantly higher than that of levodopa alone. GPC shows obvious effects in improving patients' motor syndrome and the quality of life; as used in combining with levodopa, the dosage of levodopa required could be reduced.

[Observation on therapeutic effect of electroacupuncture at points Baliao and Huiyang (BL 35) on retention of urine induced by spinal cord injury].

OBJECTIVE: To explore a more effective therapy for retention of urine induced by spinal cord injury. METHODS: Eighty-four cases were randomly divided into a treatment group of 46 cases and a control group of 38 cases. The treatment group were treated with electroacupuncture at Baliao and Huiyang (BL 35), and the control group with electroacupuncture at acupoints routinely selected. RESULTS: The total effective rate and the cured rate were 82.6% and 43.5% in the treatment group and 63.2% and 23.7% in the control group respectively, with a very significant difference between the two groups (P < 0. 01). CONCLUSION: Electroacupuncture at Baliao and Huiyang (BL 35) has obvious therapeutic effect on retention of urine induced by spinal cord injury.