Effects of Patient-Controlled Transcutaneous Electrical Acupoint Stimulation on Cancer Induced Bone Pain Relief in Patients with Non-Small Cell Lung Cancer: Study Protocol for a Randomized Controlled Trial.

Background: Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC). Methods/Design: This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight. Discussion: PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP. Trial Registration: ClinicalTrials.gov NCT05730972, registered February 16, 2023.

Transcutaneous electrical acupoint stimulation for cancer-related pain management in patients receiving chronic opioid therapy: a randomized clinical trial.

PURPOSE: The opioid crisis resulting from its use disorder and overdose poses additional challenges for cancer pain management. The American Society of Clinical Oncology Practice Guideline recommends acupuncture therapy for the management of adult cancer-related pain (CRP), but the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on CRP remains uncertain. METHODS: This 5-week prospective randomized clinical trial was conducted at 2 hospitals in China, and participants with CRP receiving chronic opioid therapy were randomized 1:1 into two groups between December 2014 and June 2018. The true TEAS group underwent 15 sessions of TEAS treatments over 3 consecutive weeks, while the control group received sham stimulation. The primary outcome was the numerical rating scale (NRS) score in the past 24h at week 3. The secondary outcomes included morphine equivalent daily dose, quality of life and adverse events. RESULTS: A total of 159 participants were included in the modified intention-to-treat population. The baseline characteristics were similar in both groups. The mean NRS scores were 0.98 points at week 3 in the true TEAS group and 1.41 points in the sham group, with the mean difference between groups of -0.43 points (P < 0.001; OR = 0.68, P < 0.05). The proportion of patients with NRS reduction more than thirty percentage at week 3 was 50.00% in the true TEAS group and 35.44% in the sham group (RD = 0.15, P > 0.05; RR = 1.41, P > 0.05). No significant difference in pain intensity between the two groups was observed during the follow-up period without TEAS intervention (week 4, OR = 0.83, P > 0.05; week 5, OR = 0.83, P > 0.05). The Karnofsky Performance Status value suggested that patients in the true TEAS group experienced an improved quality of life (Between-group differences: week 3, 3.5%, P < 0.05; week 4, 4.6%, P < 0.001; week 5, 5.6%, P < 0.001). CONCLUSIONS: The 3-week application of TEAS in patients with CRP receiving chronic opioid therapy resulted in a statistically significant reduction in pain scores, but the observed reduction was of uncertain clinical significance. The prolonged analgesic effect of TEAS was not confirmed in this trial. CLINICALTRIAL: GOV: ChiCTR-TRC-13003803.

Traditional Chinese medicine treatment for COVID-19: An overview of systematic reviews and meta-analyses.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies. OBJECTIVE: This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM. SEARCH STRATEGY: Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as "Chinese medicine," "Lianhua Qingwen" and "COVID-19" were used. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included. DATA EXTRACTION AND ANALYSIS: A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently. RESULTS: There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay. CONCLUSION: Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.

Analysis of the Characteristics of Dominant Diseases in Traditional Chinese Medicine: Based on 95 Diseases.

Background: Traditional Chinese medicine (TCM) has been widely used all over the world and has shown its superiority in some diseases. However, there are no clear evaluation criteria for TCM. In 2019, a list of TCM dominant diseases was published by the Chinese National Administration of Traditional Chinese Medicine. This study aimed to systematically summarize the characteristics of 95 TCM dominant diseases and provide a reference for the establishment of evaluation criteria for TCM dominant diseases. Methods: The diagnosis and treatment protocols of all the 95 TCM dominant diseases were screened. The data of disease classification, diseases' code of TCM, length of hospital stay, treatment protocols, and clinical pathways were reviewed and summarized. Results: The diseases of the genitourinary and nervous systems accounted for 14.74% and 12.73% of the TCM dominant diseases, respectively. The length of hospital stay for 55 (57.89%) diseases was no more than less than 14 days. Each disease had its specific Chinese herbal decoction pieces and Chinese patent drugs. Chinese medical injections were not widely used. TCM external treatments for these diseases are abundant, with hundreds optional. Conclusion: Some potentially promising TCM dominant diseases remain to be identified and deserve further research to establish the evaluation criteria of TCM dominant diseases.

Efficacy and Safety of Chinese Medicine for COVID-19: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of traditional Chinese medicine for COVID-19 treatment with a focus on the benefits of symptomatic relief and time-related indexes. Seven electronic databases (PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data, and Chinese Clinical Trial Registry) were systematically searched from their beginning to April 2021. Only randomized controlled trials (RCTs) comparing patients using Western therapy (WT) alone and those using additional Chinese medicine (WT [Formula: see text] CM) were included. Primary outcomes included overall efficacy, lung recovery, and time to viral assay conversion. Secondary outcomes included time and rate of individual symptom recovery, laboratory indicators, and adverse events. Overall, 15 RCTs, including 1469 participants, were included in this review. WT [Formula: see text] CM significantly improved overall efficacy (risk ratio, RR [Formula: see text] 1.21; 95% CI: 1.12 to 1.30; [Formula: see text] [Formula: see text] 0.01) and lung recovery (RR [Formula: see text] 1.30; 95% CI:1.19 to 1.42; [Formula: see text] [Formula: see text] 0.01) and shortened the time to viral assay conversion (weighted mean differences, WMD [Formula: see text]1.38; 95% CI: -1.98 to -0.78; [Formula: see text] [Formula: see text] 0.01) and duration of chest distress (WMD [Formula: see text] 2.41; 95% CI: -2.99 to -1.83; [Formula: see text] [Formula: see text] 0.01) compared to WT alone. There was no difference in safety between the WT [Formula: see text] CM and WT groups (RR [Formula: see text] 0.94; 95% CI: 0.64 to 1.39; [Formula: see text] 0.76). In conclusion, the synthesized evidence from 15 RCTs showed that additional Chinese medication may improve treatment efficacy, relieve symptoms, promote lung recovery, and reduce the inflammatory response against COVID-19, while not increasing the risk of adverse events compared with conventional Western medication alone.

Comparative effect of electroacupuncture with different frequency on headache attacks in migraine outpatients: study protocol for a randomised placebo-controlled trial.

BACKGROUND: Headache attacks severely impaired life quality and increase the economic burden of migraineurs. Electroacupuncture (EA) has been used worldwidely to treat several pain-related diseases including migraines. However, whether EA with low or high frequency exerts a distinct analgesic effect remains unknown and needs further study. METHODS/DESIGN: This study is a randomised, single-blinded, placebo-controlled trial with three parallel arms. A total of 144 migraine outpatients will be randomly allocated to the 2 Hz EA group, 100 Hz EA group and placebo control group. The duration of the trial is 20 weeks, including a 4-week-long baseline assessment period (weeks - 4-0), a 4-week-long treatment period (weeks 1-4) and a 12-week-long follow-up period (weeks 5-16). Twelve treatment sessions will be performed over a 4-week period (weeks 1-4). The primary outcome will be measured by the frequency of migraine attacks in the past 4 weeks at the end of week 4 post-randomisation. The secondary outcome will be measured by the frequency of migraine attacks in the past 4 weeks at the end of weeks 8, 12 and16 post-randomisation; number of days with migraine; dosage of ibuprofen; the scores of visual analogue scale (VAS); Self-Rating Anxiety Scale (SAS); Self-Rating Depression Scale (SDS); and Migraine Specific Quality of Life questionnaire (MSQ) in the past 4 weeks at the end of weeks 4, 8, 12 and 16 post-randomisation. Safety assessment, compliance and blinding evaluation will be carried out at the end of week 16 post-randomisation. DISCUSSION: The recruitment will be started on 1 June 2021 and expected to finish on 31 May 2023. We aimed to clarify the dominant frequency of EA on headache attacks in a migraineur. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-1800017259 . Registered on 20 July 2018.

Evaluating the analgesic effect and advantage of transcutaneous electrical acupoint stimulation combined with opioid drugs for moderate to severe cancer-related pain: a study protocol for a randomized controlled trial.

BACKGROUND: Transcutaneous electrical acupoint stimulation (TEAS), which is also known as acupuncture-like transcutaneous electrical nerve stimulation (TENS), has been widely used in acute or chronic pain. However, previous research has not demonstrated that TEAS is effective for cancer-related pain. Opioid drugs are strongly recommended for treating cancer-related pain, but opioid-induced immunosuppression is still the most intractable drug-induced medical problem. Evaluating the efficacy and potential advantage of TEAS combined with opioid drugs in moderate and severe cancer-related pain in China is important because such studies are lacking. METHODS/DESIGN: This trial is a multicenter, prospective randomized controlled clinical trial. In total, 160 patients who were enrolled from two hospitals in the Zhejiang Province (China) will be randomly allocated into two groups: a TEAS group and sham TEAS group without acupoint electrical stimulation. Both groups will receive a 21-day interval of chemotherapy and conventional cancer pain therapy. Fifteen treatment sessions will be performed over a three-week period. The primary outcomes will be measured by changes in the Numerical Rating Scale (NRS) scores and equivalent dosage of morphine at baseline, three weeks of treatment and one two-week follow-up. The secondary outcome measures include cellular immunity function, life quality assessment, opioids side effects assessment, and safety and compliance evaluation. DISCUSSION: This trial is expected to clarify whether TEAS is effective for cancer-related pain. These results demonstrate the advantage of TEAS combined with opioid drugs on improving immune function and decreasing opioid induced side effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-13003803 . Registered on 27 August 2013.

The Application of Nanotechnology in the Codelivery of Active Constituents of Plants and Chemotherapeutics for Overcoming Physiological Barriers during Antitumor Treatment.

Antitumor therapy using a combination of drugs has shown increased clinical efficacy. Active constituents derived from plants can offer several advantages, such as high efficiacy, low toxicity, extensive effects, and multiple targets. At present, the combination of plants' active constituents and chemotherapeutic drugs has attracted increased attention. Nanodrug delivery systems (NDDSs) have been widely used in tumor-targeted therapy because of their efficacy of delivering antitumor drugs. The in vivo process of tumor-targeted NDDSs has several steps. They include blood circulation, tumor accumulation and penetration, target cell internalization and uptake, and drug release and drug response. In each step, NDDSs encounter multiple barriers that prevent their effective delivery to target sites. Studies have been performed to find alternative strategies to overcome these barriers. We reviewed the recent progress of codelivery of active constituents of plants and chemotherapeutics using NDDSs. Progress into transversing the physiological barriers for more effective in vivo antitumor delivery will be discussed in this review.

Hyperthermia exacerbates the effects of cathepsin L on claudin-1 in a blood-brain barrier model in vitro.

PURPOSE: The effects of cathepsin L on claudin-1 expression were investigated under hyperthermic condition in a blood-brain barrier (BBB) model in vitro, in order to estimate the potential effects of hyperthermia on BBB dysfunction. MATERIALS AND METHODS: Brain microvascular endothelial cells (BMECs) and astrocytes were obtained from rat brain. The BBB models were randomly divided into a sham (37°C) group, a 39°C group, a 37°C+cathepsin L group and a 39°C+cathepsin L group. The permeability of BBB was judged. The expressions of cathepsin L in astrocytes and claudin-1 in BMECs were detected using immunohistochemistry method and western blot assay. RESULTS: The permeability of BBB models was higher in the 39°C group than in the sham group. The cathepsin L expression in astrocytes was higher in the 39°C group than in the sham group (P<0.01), whereas the claudin-1 expression in BMECs was lower in the 39°C group than in the sham group (P<0.01). The claudin-1 expression in BMECs was significantly lower in the 37°C+cathepsin L group than in the sham group (P<0.01). At the same time point, the claudin-1 expression in BMECs was significantly lower in the 39°C+cathepsin L group than in the 37°C+cathepsin L group (P<0.01). CONCLUSION: Hyperthermia can probably decrease claudin-1 expression in BMECs by upregulating cathepsin L expression in astrocytes in a BBB model in vitro.

Epidemiology and microbiology of nosocomial bloodstream infections: analysis of 482 cases from a retrospective surveillance study.

In many traditional Chinese medicine (TCM) hospitals, most patients are elderly with chronic diseases. Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality. A retrospective surveillance study was performed to examine the epidemiology and microbiology of nBSIs in a TCM hospital from 2009 to 2011. A total of 482 patients with nBSIs were included in the study period. The incidence rate was 5.7/1000 admissions. Escherichia coli (25.5%) was the most common Gram-negative and coagulase-negative staphylococcus (CoNS) (14.1%) was the most common Gram-positive organism isolated. One-third of the E. coli and Klebsiella pneumoniae isolated from the nBSIs were the third-generation cephalosporin-resistant. Half of the Acinetobacter species isolates were resistant to imipenem. Of all the CoNS isolates, 90.7% were resistant to methicillin. Carbapenems and glycopeptide were the most frequently used for nBSI therapy. Only about one-third of patients (157/482) received appropriate empirical therapy. Septic shock, hemodialysis, Pitt bacteremia score >4, urinary tract infection, and appropriate empirical therapy were most strongly associated with 28-d mortality. The incidence of nBSIs was low in the TCM hospital but the proportion of nBSIs due to antibiotic-resistant organisms was high. A high Pitt bacteremia score was one of the most important risk factors for mortality in nBSIs. Therefore, the implementation of appropriate empirical therapy is crucial to improve the clinical outcome of nBSIs.

Integrative medicine for subacute stroke rehabilitation: a study protocol for a multicentre, randomised, controlled trial.

INTRODUCTION: Many patients with stroke receive integrative medicine in China, which includes the basic treatment of Western medicine and routine rehabilitation, in conjunction with acupuncture and Chinese medicine. The question of whether integrative medicine is efficacious for stroke rehabilitation is still controversial and very little research currently exists on the integrated approach for this condition. Consequently, we will conduct a multicentre, randomised, controlled, assessor-blinded clinical trial to assess the effectiveness of integrative medicine on stroke rehabilitation. METHODS AND ANALYSIS: 360 participants recruited from three large Chinese medical hospitals in Zhejiang Province will be randomly divided into the integrative medicine rehabilitation (IMR) group and the conventional rehabilitation (CR) group in a 1:1 ratio. Participants in the IMR group will receive acupuncture and Chinese herbs in addition to basic Western medicine and rehabilitation treatment. The CR group will not receive acupuncture and Chinese herbal medicine. The assessment data will be collected at baseline, 4 and 8 weeks postrandomisation, and then at 12 weeks' follow-up. The primary outcome is measured by the Modified Barthel Index. The secondary outcomes are the National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment, the mini-mental state examination and Montreal Cognitive, Hamilton's Depression Scale and Self-Rating Depression Scale, and the incidence of adverse events. ETHICS AND DISSEMINATION: Ethical approval was obtained from ethics committees of three hospitals. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone, during follow-up calls inquiring on patient's post-study health status. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Register: ChiCTR-TRC-12001972, http://www.chictr.org/en/proj/show.aspx?proj=2561.

[A blind technique used in randomized controlled trials of treatment based on changes of syndromes].

Treatment based on syndrome differentiation is an essential feature of traditional Chinese medical diagnosis. The interventions based on changes of syndrome types in randomized controlled trials are complicated, leading to the difficulty of blind method enforcement. This article described a double-blind method. It could be used in randomized controlled trials under the condition of different syndrome types and different medications. It numbered drugs in two stages, and in two phases to achieve double-blind. This method not only guaranteed investigators and subjects to be in blinded conditions, but also achieved using different medications for patients of different syndromes. It also caused no drug waste. It was scientific and feasible.

Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial.

BACKGROUND: Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. METHODS/DESIGN: In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. DISCUSSION: This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-12001971.

[The application of single-arm clinical trials with objective performance criteria in clinical research of traditional Chinese medicine].

Clinical research of Chinese medicine, due to its own features, is not suitable to be studied by randomized controlled trial methods in some cases. The single-arm clinical trials with objective performance criteria could be taken as a more ideal alternative method. In this paper the basic principles of single-arm clinical trials with objective performance criteria was introduced. Correlated problems of the selection of therapeutic efficacy index, the target identification, case standards, sample size calculation, statistical inference, and interpretation of results were also addressed. This method was scientific and feasible. It can partially solve some problems in the clinical research of Chinese medicine. It has better application prospect.