Efficacy and Safety of the Chinese Herbal Compound TJAOA101 in Treating Diminished Ovarian Reserve: A Protocol for Multicenter, Prospective, and Pre-Post Study

Objective Diminished ovarian reserve(DOR)can lead to early menopause,poor fecundity,and an increased risk of disorders such as osteoporosis,cardiovascular disease,and cognitive impairment,seriously affecting the physical and mental health of women.There is still no safe and effective strategy or method to combat DOR.We have developed a novel Chinese herbal formula,Tongji anti-ovarian aging 101(TJAOA101),to treat DOR.However,its safety and efficacy need to be further validated.Methods In this prospective and pre-post clinical trial,100 eligible patients aged 18–45 diagnosed with DOR will be recruited.All participants receive TJAOA101 twice a day for 3 months.Then,comparisons before and after treatment will be analyzed,and the outcomes,including anti-mullerian hormone(AMH)and follicle-stimulating hormone(FSH)levels and the antral follicle count(AFC),the recovery rate of menopause,and the Kupperman index(KMI),will be assessed at baseline,every month during medication(the intervention period),and 1,3 months after medication(the follow-up period).Assessments for adverse events will be performed during the intervention and follow-up periods.Conclusion A multicenter,prospective study will be conducted to further confirm the safety and efficacy of TJAOA101 in treating DOR and to provide new therapeutic strategies for improving the quality of life in DOR patients.

Protocol to study the effects of AMPK-mTOR/PINK-Parkin dual signaling pathways on the formation of coronary heart disease showing blood stasis symptom pattern based on traditional Chinese medicine theory of“heart governing blood and vessels”

In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.

Functional and psychosocial effects of pulmonary Daoyin on patients with COPD in China:study protocol of a multicenter randomized controlled trial

BACKGROUND： Chronic obstructive pulmonary disease （COPD） is a major public health problem worldwide. Pulmonary rehabilitation （PR） is an established intervention for the management of patients with COPD. Exercise training is an important part of PR, and its effectiveness in patients with COPD is well established. However, alternative methods of PR training such as Daoyin have not been appropriately studied. Hence, alternative forms of exercise training that require less exercise equipment and no specific training place should be evaluated. This paper describes the study protocol of a clinical trial that aims to determine if pulmonary Daoyin training will improve the exercise capacity and psychosocial function of patients with COPD in China. METHODS AND DESIGN： A multicenter, randomized, controlled trial will be conducted. A total of 464 patients meeting the inclusion criteria will be enrolled into this study with 232 patients in each of the trial group and the control group. Based on patient education, patients in the trial group will receive pulmonary Daoyin and continue with their usual therapy for three months. In the control group, patients will continue with their usual therapy. The primary outcome measures are exercise capacity assessed by the six-minute walking distance test and lung function. Secondary outcomes include dyspnea and quality of life. Measurements will be taken at baseline （month 0） and after the study period （month 3）. DISCUSSION： It is hypothesized that pulmonary Daoyin will have beneficial effects in improving exercise capacity and psychosocial function of patients with stable COPD, and will provide an alternative form of exercise training that is accessible for the large number of people with COPD. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is NCT01482000.

A study protocol of population-based cancer screening cohort study on esophageal,stomach and liver cancer in rural China

Objective:National Health Commission of the People's Republic of China collaborated with many ministries and commissions government and initiated a population-based cancer screening program in high-risk area of rural China,targeting three types of cancer that are most prevalent in these areas,including esophageal,stomach and liver cancer.This study protocol was reported to show the design and evaluate the effectiveness of cancer screening and appropriate screening strategies of three cancers in rural China.Methods and analysis:A two-step design with cancer risk assessment based on questionnaire interview,Hepatitis B surface antigen(HBsAg)test strip and subsequent clinical intervention for high-risk populations was adopted&ee of charge at the local hospitals designated in the program.Ethic and dissemination:This study was approved by the Institutional Review Board of Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College.The results will evaluate the effectiveness of cancer screening and appropriate screening strategies in rural China.

Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.

Exploring the mechanism of Xingnao Kaiqiao acupuncture method for ischemicstroke based on EEG dynamic changes: a study protocol of an exploratory,prospective,interventional trial

Background: The Xingnao Kaiqiao acupuncture method, founded by Academician ShiXuemin, has outstanding efficacy in the treatment of ischemic stroke and has been widelyused at home and abroad. However, after half a century of animal experiments and clinicalstudies, clearly and intuitively revealing its therapeutic mechanism is still a great challengefor researchers. Therefore, this experiment is based on the combination of medicine andengineering to study the immediate effects of the acupuncture method in treating patientsby recording the electroencephalography (EEG) activities of subjects during the acupunctureprocess and to further reveal the therapeutic mechanism at the brain level. Methods: Thistrial is an exploratory, prospective, single-arm interventional study involving a total ofpatients with ischemic stroke. Physicians will record EEG data from patients duringacupuncture as the primary outcome indicator. After pre-processing the EEG data,researchers will use various methods to analyze the immediate effects of acupuncture toobtain brain effectiveness. Deep learning will then be used to identify acupoint stimuli andreceive correspondence between the acupuncture effect and the brain’s internal state.National Institutes of Health Stroke Scale score before and after the acupuncture process willbe used as the secondary outcome indicator. Conclusion: This is the first study protocol toapply dynamic changes in EEG to explore a range of mechanisms of action of acupuncture inthe treatment of ischemic stroke. We propose a method to analyze EEG signals ofacupuncture patients. The deep learning model will be applied for supervised training toobtain the compelling relationship between the acupuncture method and internal brainstates, providing a new prospect for the digitization of traditional Chinese medicine.

Effect of Xingnao-Jianshen granules in treating AIS patients:study protocol for a non-randomized controlled intervention trial

Objective:Acute ischemic stroke(AIS)is characterized by high morbidity and high mortality.In recent years,complementary and alternative medicine has gradually been widely accepted and applied.At present,traditional Chinese medicine therapy and standard treatments are used for the treatment of AIS.Xingnao-Jianshen prescriptions(XNJS)is an effective prescription for the clinical treatment of AIS,but there is a lack of large-scale clinical evidence to confirm its clinical efficacy.Therefore,our team designed this protocol to evaluate the initial therapeutic effect of XNJS.Methods:The protocol for a non-randomized controlled trial is designed in which 72 eligible patients will be allocated to one of two groups.The control group(n=36)will receive standard treatment for AIS,the test group(n=36)will receive XNJS and standard treatment.Patients will be recruited after stroke onset and will receive the intervention continuously over 10±1 days,with a follow-up period of 90 days.The primary outcome will be the change in the NIHSS,BI,mRS scores.All outcome measures will be assessed at inception,after the intervention(10±1 days),and at the follow-up(90 days).The results will be disseminated to the public through peerreviewed journals and academic conferences.Discussion:The study will provide evidence of the preliminary effects.

National Nutrition and Health Systematic Survey for Children 0–17 Years of Age in China

The main purpose of the National Nutrition and Health Systematic Survey for children 0-17 years of age in China(CNHSC)was to collect basic data on the nutrition,development,and health status for children in different regions across China using evidence-based,reliable,and cost-effective approaches.Children and their parents or guardians from seven regions(south,southwest,north,northwest,eastern,central,and northeast China)in China were recruited.A multi-stage stratified randomized sampling method was used.Two provinces were randomly sampled from each of the seven regions,from which one urban district and one rural country were also randomly sampled,resulting in a total of 28 survey counties/districts.Dietary surveys,health examinations,laboratory testing,and questionnaires were used to collect dietary intake,nutritional status,child development,and health status information.Nutrition,health,and lifestyle assessment of children and their parents was determined using the Knowledge Attitude Practice(KAP)survey.Greater than 100,000 children(38,000 children<6 years of age and 66,000 children6-17 years of age)completed the survey.The survey provided comprehensive data on child nutrition and health status for future studies and will serve as the basis for an integrated nutrition and health improvement strategies proposal for children in China.

Efficiency and safety of acupuncture for women with premature ovarian insufficiency:study protocol for a randomized controlled trial

Acupuncture has been widely used as an alternative and complementary therapy for premature ovarian insufficiency(POI)in China.However,research to date has not shown that acupuncture is effective for POI compared with hormone replacement therapy(HRT).We will conduct a randomized,controlled,and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on POI.Seventy-six patients with POI will be randomly assigned to two groups.The treatment group will receive twenty-eight one-hour sessions of acupuncture treatments,and the control group will receive 12-week HRT.The whole study will consist of a 12-week treatment plan and a 12-week follow-up session.The primary outcome is measured by changes in serum anti-Müllerian hormone and follicle-stimulating hormone(FSH)levels at weeks 12 and 24.Secondary outcome measures include estradiol,luteinizing hormone(LH),LH/FSH ratio,Kupperman index,and menstrual condition.This trial is expected to clarify whether or not acupuncture is effective and safe for POI compared with HRT.

Efficacy of press needle on immune function and quality of life in female breast cancer patients after radical mastectomy:study protocol for a randomized controlled trial

Radical mastectomy may lead to suppression of cellular immune function in patients with malignant tumors,and affect the quality of life(QOL)of patients.Immune suppression is a common cause of complications and adverse reactions in adjuvant therapy after radical mastectomy of breast cancer.Currently,there are few proven effective treatments for immune suppression.Therefore,it’s necessary to develop a new treatment method.Press needle is widely used in clinical practice.However,there have been relatively few studies that evaluate the effects of press needle on postoperative immune function.The aim of the present study is to assess the effects of press needle on immune function and QOL in female breast cancer patients undergoing radical mastectomy.This study will be a single-center,randomized and single-blinded trial.Totally 78 eligible patients will be randomized in a ratio of 1:1 to the press needle group or the sham press needle group.During the treatment phase,patients will undergo five times weekly of verum press needle or sham press needle for 2 weeks.The primary outcome measures will be the peripheral blood levels of CD8^(+),CD4^(+),CD3^(+),and CD4^(+)/CD8^(+)T cells.The secondary outcome measures will be the changes of patients’QOL,evaluated by the Karnofsky Performance Scale score and the EORTC core quality of life questionnaire(EORTC QLQ-C30).Furthermore,5-year survival rate and recurrence rate will be evaluated.Safety and adverse events will be assessed at each visit.The results of this on-going study will provide clinical evidence for the effects and safety of press needle on immune function and QOL in patients after breast cancer resection compared with sham press needle.

Evaluation of the effect of acupuncture on hand pain,functional deficits and health-related quality of life in patients with rheumatoid arthritis--A study protocol for a multicenter,double-blind,randomized clinical trial

BACKGROUND： Rheumatoid arthritis（RA） is a systemic inflammatory disease characterized by functional disability and pain. Although acupuncture is widely used, until now Western acupuncture studies on RA have not shown conclusive positive results. Acupuncture is regarded as a reflex therapy that has effects on the human autonomic nervous system. By establishing a traditional Chinese medicine（TCM） diagnosis first, the practitioner is able to choose acupoints according to the state of each individual patient.METHODS/DESIGN： We are interested if acupuncture, using a classical diagnostic procedure to allocate acupoints to the patient according to the Shang Han Lun theory, can be effective in relieving pain, improving hand function and increasing health-related quality of life in RA.The authors intend to harmonize TCM diagnosis according to clinical and genetic profiles. Patients with the TCM diagnosis of a so-called Turning Point syndrome will be followed up in a randomized, prospective, double-blind, placebo-controlled, multicenter and three-armed parallel-group study with a standardized treatment in order to optimize potential therapeutic effects of acupuncture on pain, strength and muscle function of patients with RA as well as the influence on inflammation and quality of life.DISCUSSION： The findings of this study will provide important clinical information about the feasibility and efficacy of acupuncture treatment for RA patients. In addition, it will explore the feasibility of further acupuncture research.TRIAL REGISTRATION NUMBER： Clinical Trials.gov Identifier NCT02553005.

Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer:protocol for a randomized double-blind controlled trial

BACKGROUND： Traditional Chinese medicine （TCM） is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer （NSCLC） are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC. METHODS AND DESIGN： This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles Progression-free survival （PFS） is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life （EORTC QLQ-LC43, and TCM syndrome score） Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed. DISCUSSION： Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.

Defining Acupuncture-Moxibustion：A Delphi Study Protocol

Background： With the worldwide use and modern development of acupuncture-moxibustion, there is disagreement on its basic definition. There has been an obstacle for clinical practice, research, and legislation. Considering this challenge, the World Federation of Acupuncture-Moxibustion Societies proposes to develop the definition and basic scope of acupuncture-moxibustion with a Delphi study. Methods： A reactive Delphi method will be used to ask a group of experts to rate the relevance and clarity of a predesigned initial item list. This list was generated by the steering committee through a literature review and group discussion. Forty experts will be selected from many disciplines and continents to ensure appropriate representation. Predefined rules will be applied to modify the items until a consensus is achieved. After achieving the consensus on all items through the survey round, the steering committee will form the definition and basic scope of acupuncture-moxibustion by organizing a literal statement with a detailed explanation.

Electroacupuncture for the prevention of postoperative gastrointestinal dysfunction in patients undergoing vascular surgery under general anesthesia: study protocol for a prospective practical randomized controlled trial

BACKGROUND： Postoperative gastrointestinal dysfunction（PGD） is one of the most common complications following major surgeries under general anesthesia（GA）. Despite ongoing research and new drug treatments, abdominal distension within 24 h postoperatively occurs in 8%–28% of all surgeries. We aim to analyze the effectiveness of preventing PGD by preoperatively stimulating Neiguan（PC6）, Zusanli（ST36） and Shangjuxu（ST37） bilaterally twice a day compared with sham-acupuncture treatment and standard treatment.METHODS AND DESIGN： This is a single-center, prospective practical randomized controlled trial. All groups will be given standard treatments. Patients undergoing vascular surgery under GA will be included from the Vascular Surgery Unit in West China Hospital of Sichuan University, China, and divided into three groups. The experimental group will receive routine treatments and acupuncture at PC6, ST36 and ST37 bilaterally with electrical stimulation twice a day for 20 min preoperatively. The sham-acupuncture group will receive pseudo-electroacupuncture at sham acupoints of PC6, ST36 and ST37, which are 1 cun away from the real acupoints. The routine-treatment group will not receive electroacupuncture. The outcomes include the incidence of abdominal distention, abdominal circumference, the degree of abdominal distension, the fi rst time of fl atus and defecation, and hospitalization duration. DISCUSSION： The results from this study will demonstrate whether preoperative electroacupuncture is an effective method for the prevention of PGD in patients undergoing vascular surgery under GA. This study may also provide a standardized acupuncture treatment for reduction of PGD. TRIAL REGISTRATION： This study is registered with the Chinese Clinical Trial Registry： Chi CTR-TRC-13003649.

The add-on effect of a Chinese herbal formula for patients with resistant hypertension: study protocol for a pilot cohort study

BACKGROUND： Despite a recent American Heart Association （AHA） consensus statement emphasizing the importance of resistant hypertension （RH）, its control is still a challenge for conventional medicine. The Chinese herbal formula, Qutan Huayu Fang, has been used effectively to assist antihypertensive agents in blood pressure control, but its effect for RH patients is still unclear. This pilot study aims to explore the effects of taking the formula in addition to antihypertensive medication in the management of RH. METHODS/DESIGN： A prospective cohort study will be conducted in two first-class hospitals of traditional Chinese medicine （TCM）. Eligible RH patients will be classified as the experimental group （n = 100） and the control group （n = 100） based on the interventions they receive. Participants taking antihypertensive agents and the Chinese herbal formula will be in the experimental group and those taking antihypertensive agents alone will be in the control group. The whole study will last 24 weeks, including an 8-week observation and follow-up at 24 weeks. The primary outcomes, assessed against patient baseline conditions, will be the reduction of systolic blood pressure and diastolic blood pressure as well as changes in TCM symptoms and signs. These outcomes will be assessed at weeks 2, 4, 6, and 8. The reductions of blood pressure will also be assessed at week 24. Cardiac events and mortality rate will be secondary outcomes and will be assessed at weeks 8 and 24. Any adverse reactions will be recorded during the study. The causal inference method will be used to assess the effectiveness of the inclusion of TCM herbal medicine in the management of patients with RH. DISCUSSION： This study will determine whether the Chinese herbal formula is helpful for RH patients treated with antihypertensive agents and the findings will provide a basis for further confirmatory studies TRIAL REGISTRATION NUMBER： ClinicalTria/s.gov Identifier NCT01904695

Health effects of natural spring waters:A protocol for systematic reviews with a regional case example

BACKGROUND： Spring water therapies have been used since at least 1550 BC. Despite the growing body of evidence supporting these therapies for a range of conditions, including musculoskeletal, dermatological, respiratory and cardiovascular conditions, they do not currently form part of mainstream healthcare in many countries. The protocol established in this paper aims to support systematic reviews that examine the health outcomes associated with human exposure to regional spring waters, using the Australia and New Zealand context as a case study. METHODS/DESIGN： The protocol searches for studies in eight health/medical databases, searches three local health/medical journals, and includes forwards and backwards searching. Standard systematic review methods are used including： specifying pre-deterrnined inclusion criteria and data management plans, appraising the studies for bias, and allocation to a hierarchy of evidence. DISCUSSION： The protocol supports a review and comprehensive synthesis of the current evidence regarding the health effects of natural spring water, and can be adapted for reviews in other regions. From this evidence, recommendations regarding practice and future research can be made on the therapeutic role of spring water.

Effectiveness of two different acupuncture strategies in patients with vulvodynia Study protocol for a pilot pragmatic controlled trial

Background： Vulvodynia, or vulvar pain, is a common condition in women; however, there are few evidence-based clinical trials evaluating nonpharmacological therapies for this condition. Acupuncture is one complementary and integrative medicine therapy used by some patients with vulvodynia. This study evaluates two different acupuncture strategies for the treatment of vulvodynia and aims to evalu- ate whether either of the acupuncture protocols reduces vulvar pain, pain duration or pain with inter- course. The study also examines how long the effect of acupuncture lasts in women with vulvodynia. Methods/design： The study is designed as a randomized controlled trial, focused on two acupuncture protocols. Fifty-one patients who have had vulvodynia for more than 3 months will be recruited. Among them, 34 patients will be randomized into Groups la and 1b; those who are unwilling to receive acupuncture will be recruited into the standard care group （Group 2）. Patients in Group la will have acupuncture focused on the points in the pudendal nerve distribution area, while patients in Group lb will receive acupuncture focused on traditional （distal） meridian points. Patients in Group 2 will receive routine conventional treatments, such as using pain medications, local injections and physical therapies or other nonsurgical procedures. Acupuncture will last 45 min per session, once or twice a week for 6 weeks. The primary outcome measurement will be objective pain intensity, using the cotton swab test. The secondary outcome measurement will be subjective patient self-reported pain intensity, which will be conducted before cotton swab test. Pain intensities will be measured by an 11-point Numeric Pain Rating Scale. Pain duration and pain score during intercourse are recorded. Local muscle tension, tender- ness and trigger points （Ashi points） are also recorded. All measurements will be recorded at baseline （before the treatment）, at the end of each week during treatment and at the end of the 6weeks. Follow-up will be done 6 weeks following the last treatment. Discussion： Results of this trial will provide preliminary data on whether acupuncture provides better outcomes than nonacupuncture treatments, i.e., standard care, and whether acupuncture focused on the points in pudendal nerve distribution, near the pain area, has better results than traditional acupunc- ture focused on distal meridian points for vulvodynia.