Annual advances of acupuncture research in 2021

Lei Wang,Jia-Qi Li,Qi Wang,Chao Gao,Qi-Lin Tang,Mei-Dan Zhao,Kai Zhang

1Department of 1th Surgery,Tianjin Gong An Hospital,Tianjin 300042,China.2Research Center of Experimental Acupuncture Science,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China.3North China University of Science and Technology,Traditional Chinese Medical College,Tangshan 063000,China.4Department of General Surgery,Tianjin General Surgery Institute,Tianjin Medical University General Hospital,Tianjin 300052,China.5School of Basic Medical Sciences,Hebei University of Chinese Medicine,Hebei 050200,China.6School of Acupuncture&Moxibustion and Tuina,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China.7Department of Acupuncture and Moxibustion,Tianjin Gong An Hospital,Tianjin 300042,China.

Abstract This paper reviews the main progress of research on acupuncture.The annual acupuncture research review includes reports on clinical and basic research on acupuncture published in 2021.From the perspective of literature types,most of them are clinical studies or systematic review,and high-quality basic studies can also be seen.Acupuncture in the treatment of cancer diseases,cardio-cerebrovascular disease,endocrine disease,digestive system diseases,inflammatory diseases and COVID-19 has certain advantages.Most clinical studies or systematic reviews show that acupuncture has played a positive role in treating many diseases,and it provides a valuable basis for further in-depth study of the clinical value of acupuncture and mechanism.The quality and innovation of acupuncture and moxibustion research are gradually improving.Researchers not only pay attention to standardized acupuncture and moxibustion treatment research,but also continue to explore new diseases,new mechanisms,and new methods.High-quality clinical studies with guiding significance have laid a solid research foundation for the international promotion of acupuncture.In terms of basic research,there are also high-quality animal experiments published in the international top biology journal Nature,which have been highly accepted internationally and increasingly recognized by international experts.Acupuncture is a very promising treatment.

Keywords:traditional Chinese medicine;TCM;acupuncture;advances;pain;cancer;inflammation;COVID-19

Highlights

This review covers studies in the year 2021 for acupuncture.In addition,acupuncture treatment of cancer-related symptoms,inflammatory diseases and COVID-19 were major themes.In terms of basic research,the anti-inflammatory mechanism of acupuncture has been further confirmed and a breakthrough has been made.In terms of clinical research,acupuncture was innovatively used to treat COVID-19 during the COVID-19 epidemic.At the same time,based on biological information and network topology research methods,the mechanism of acupuncture treatment of COVID-19 has also been further confirmed.Clinical studies of acupuncture in the treatment of cancer management symptoms are also increasing,and more and more high-quality randomized controlled clinical studies support the effectiveness of acupuncture therapy.

Background

The use of acupuncture in China dates back more than 3,000 years.Between the 16th and 19th centuries,acupuncture spread to the United States and Europe.The history of the modern study of acupuncture began in the 18th century and has developed rapidly since then [1].Acupuncture,one of the key treatments of Traditional Chinese medicine (TCM),involves inserting needles into acupoints on the body and stimulating them by hand manipulation,electrical impulses,or heat[2].In the past,doctors and scientists have struggled to apply acupuncture into clinical practice.In modern times,researchers have tried to introduce evidence-based medicine (EBM)research methods to assess its effectiveness and safety,and to further explore the underlying physiological and biological mechanisms of acupuncture [1–8].Current clinical trials suggest that acupuncture may be effective for a variety of diseases.However,due to limitations in quality and accuracy,some trials have not provided sufficient evidence to determine the effectiveness of acupuncture.Therefore,rigorous experimental design should be carried out by using EBM method,in order to obtain reliable clinical evidence.Meta-analyses and randomized controlled trials used to be served as the essential tools and sources of evidence around average results for groups of heterogeneous patients in EBM [9].We are pleasantly surprised to find that the quality of clinical studies on acupuncture and moxibustion is becoming increasingly high in recent years,which benefits from the popularity of EBM.

Looking back at the history of acupuncture research,we are pleased to see this amazing development.The evidence that acupuncture is beneficial in many cases has greatly increased our confidence in understanding the mechanisms by which acupuncture treats diseases.It is worth noting that,due to its characteristics of minimally invasive,simple operation,effective and relatively safe,acupuncture has become one of the most popular western treatment methods in TCM and has attracted more and more attention from international academic circles.As can be seen from PubMed database,the literature related to acupuncture has been rising in the last ten years (Figure 1).In 2021,acupuncture researches were focused on cancer-related symptoms,inflammatory diseases,and COVID-19.Groundbreaking research includes neuroanatomical basis for acupuncture in cancer management,electroacupuncture to drive the vagal-adrenal axis,mechanism of acupuncture in the treatment of COVID-19 and so on.Thus,this review provides a broad annual summary of the acupuncture research during the year 2021.

Figure 1 Number of papers published on acupuncture research between 2012 and 2021

Acupuncture for cancer-related symptoms

Pain

Pain is one of the most common symptoms of cancer patients.Since the etiology of cancer pain is complex and patients' comorbidities and medication should be taken into account,pain management of patients often requires multidisciplinary cooperation,including TCM.Acupuncture is considered a promising adjunctive therapy for the control of cancer pain [10].In 2021,the most exciting randomized clinical trial (RCT) was a study published inJAMA Oncology[11].This study compared the benefits of electroacupuncture (EA) and auricular acupuncture(AA)in relieving chronic musculoskeletal pain in patients with cancer.It was found that both EA group and AA group decreased pain intensity in the brief pain inventory (BPI) in comparison to usual care group;Noninferiority was not shown between AA and EA.Additionally,pain-related functional interventions and quality of life in two treatment groups have been promoted.Furthermore,subjects in EA and AA groups experienced a sustained pain reduction as well as less analgesic use than the usual care group in the following 12 weeks,and this continuously declined to 24 weeks.Mild to moderate adverse events were demonstrated for both EA and AA groups.The publication of the study shows that mainstream international medical recognition of acupuncture is growing,and its conclusions are likely to be incorporated into clinical guidelines in Europe and the United States.A systematic review also found positive results that acupuncture is safe and effective in palliative care for cancer patients [12].However,further high-quality studies are needed in the future.

Insomnia

Insomnia and pain often co-occur,which reduces the quality of life for cancer patients [13].An RCT evaluated the effects of cognitive behavioral therapy for insomnia (CBT-I) and acupuncture on pain severity in cancer cases with insomnia and pain.It was found that acupuncture helped reduce pain and insomnia,while CBT-I had a delayed effect on pain,probably through improving insomnia[14].

Reduction in quality of life caused by chemotherapy

Cancer patients experience decreased quality of life during chemotherapy.A pilot study was conducted to evaluate the initial effect and feasibility of quality of life and symptom burden in cases treated with electroacupuncture [15].The results showed that electroacupuncture had a good effect on improving quality of life,controlling symptom burden,and reducing toxic side effects during adjuvant chemotherapy.This study provides the basis for further large,multicenter studies.

Chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the side effects caused by chemotherapy.A randomized control study suggested that acupuncture alleviated CIPN neuropathic pain and improved tactile threshold[16].

Chemotherapy-induced leukopenia

Leukopenia is the most common side effect of chemotherapy and can reduce immune function,which increases patients' risk of fatal infections [17].A meta-analysis found that acupuncture may ameliorate chemotherapy-induced leukopenia by significantly increasing white blood cell and neutrophil values in patients undergoing chemotherapy.In addition,white blood cell counts increased regardless of the type of acupuncture used [18].

Acupuncture for cerebrovascular diseases

Post-stroke depression

Acupuncture is widely used in China for stroke prevention and treatment,as well as for post-stroke depression.However,the selection of acupuncture methods and acupoints has always depended largely on the experience and skills of doctors.A study comparing the effectiveness of different commonly used acupuncture methods in patients with post-stroke depression using a network meta-analysis.According to the ranking probability,scalp acupuncture plus conventional acupuncture is the most effective,followed by ear acupuncture,eye acupuncture and so on [19].

Post-stroke insomnia

A meta-analysis has found that acupuncture may be more effective than drugs in the treatment of insomnia after stroke.It also has good safety and more long-term benefits [20].

Acupuncture for cardiovascular diseases

An observational study examined the effects of acupuncture in hypertensive patients taking anti-hypertensives.The results showed that major adverse cardiovascular events,all-cause mortality,and myocardial infarction were significantly lower in the acupuncture group than in the non-acupuncture group [21].This study shows that acupuncture can reduce the cardiovascular burden in patients with high blood pressure.

Patients with chronic stable angina are often accompanied by anxiety.A systematic review has found that acupuncture can be used as an adjunct therapy to treat anxiety and depression associated with stable angina [22].

Acupuncture for diabetes

Acupuncture has been used for the treatment of type 2 diabetes for 2,000 years,with new clinical evidence and animal studies demonstrating its efficacy all the time.A systematic review has shown that acupuncture is effective in treating diabetes,improving blood lipids and blood pressure,and reducing weight.Acupuncture can be used as a complementary treatment for type 2 diabetes,especially for patients with obesity or metabolic disorders.However,due to the small sample size and poor quality of the trial methodology reviewed,the amount of evidence is not entirely convincing.There is a need for carefully planned long-term studies[23].

Acupuncture has been widely used in the treatment of diabetic peripheral neuropathy in China [24].A study aims to summarize the characteristics and evaluate the methodology quality of the systematic reviews regarding acupuncture for diabetic peripheral neuropathy.This study supports the efficacy of acupuncture,but conclusions should be drawn with caution due to the quality of the methodology included in the study [24].

Acupuncture for gastrointestinal disorders

A meta-analysis found that acupuncture was significantly associated with relief of functional gastrointestinal disorders symptoms [25].This study adds to the clinical evidence of acupuncture treatment of gastrointestinal diseases.

Acupoint specificity has always been one of the hot issues in acupuncture research.A clinical study comparing the effectiveness of EA at different acupoints.The results showed that electroacupuncture bothZusanli(ST36) andZhongwan(CV12) were more effective thanZhongwan(CV12) alone [26].

Opioid analgesics are one of the most effective analgesics,but may cause constipation.A meta-analysis confirmed the therapeutic effects of acupuncture in the treatment of opioid-induced constipation (OIC)[27].Combined acupuncture and drug intervention can improve the prognosis of OIC patients more than monotherapy.

Acupuncture for inflammation-related diseases

Research performed by Liu et al.explored the mechanism of acupuncture in driving the vagal–adrenal axis at ST36 acupoint.First,by generatingProkr2Adv-tdTomatomice,they demonstrated that PROKR2-Cre-labeled myelinated neurons were mainly enriched in the dorsal root ganglia (DRG) innervating limb segments,and the neuron specifically innervated deep hindlimb fascial tissues,rather than abdominal fascial tissues.Subsequently,they knocked on PROKR2Cre-marked sensory neurons in the DRG and found that low-intensity acupuncture of hindlimb at ST36 acupoint failed to activate anti-inflammatory effects of vagus-adrenal axis,however,this did not affect the sympathetic anti-inflammatory induced by high-intensity stimulation of hind limb acupuncture point ST36 and abdominal acupuncture pointTianshupathways.Then,they reported that vagus-adrenal axis was driven by optogenetics of PROKR2Cre-marked nerve terminals in ST36,rather than sympathetic reflexes.Finally,they tested the structural basis for the anti-inflammatory effect induced by low-intensity EA stimulation based on the tissue innervation pattern of PROKR2-Cre-labeled sensory fibers.This study provides the basis of neuroanatomy for different acupoints in driving specific autonomic pathways to treat diseases such as systemic inflammation (Figure 2) [28].

Acupuncture for infectious diseases

Acupuncture has been widely used to treat COVID-19 during the COVID-19 epidemic.Bioinformatics/topology studies have found that acupuncture may play a positive role in the treatment of COVID-19,possibly by inhibiting inflammatory stress,regulating neurological function,and improving immune function [29].

An interesting case report was recently published describing an anesthesiologist and acupuncturist who developed symptoms of pneumonia after being infected with COVID-19,including pleural and chest pain and breathing difficulties,and was treated with self-acupuncture until he recovered [30].The use of acupuncture in the treatment of COVID-19 was a hot research topic in 2021 [31–43].Research types mainly focus on clinical studies and evidence-based medicine studies,but there are few high-quality randomized controlled studies.Based on the anti-inflammatory and modulates immunity effect of acupuncture,most scholars have speculated that acupuncture may play a positive role in the rehabilitation of COVID-19.Due to its relative safety,clinicians have tried to use acupuncture in the treatment and rehabilitation of COVID-19,and preliminary data have been obtained.The results were mostly positive,and acupuncture is considered as easy to popularize,inexpensive,and effective treatment for COVID-19 prevention,treatment,rehabilitation,and control of complications and primary diseases of COVID-19.The mechanism of acupuncture in the treatment of COVID-19 is summarized in Figure 3.

Figure 2 Mechanism of acupuncture anti-inflammatory at ST 36

Figure 3 Mechanism of acupuncture in the treatment of COVID-19 (Image has been modified based on Beijing Medipear Information Technology Co.,Ltd.)

Acupuncture for rheumatic diseases

A randomized controlled study found that though both distal point and proximal point acupuncture can improve symptoms in participants with ankylosing spondylitis,while the distal acupoint group had higher and longer-lasting clinical efficacy [44].This study enriches the content of acupoint compatibility and has important clinical application value.

Conclusion and prospective

More and more studies on acupuncture have been published internationally (Table 1).At the same time,we also find that the quality of both clinical and basic research is constantly improving.The diseases treated by acupuncture are not limited to the diseases of nervous system and skeletal muscle system,but have been extended to many clinical fields,especially in the breakthrough research on the treatment of cancer,inflammatory diseases,and infectious diseases.From the literature in recent years,fortunately,we found that the quality of clinical studies of acupuncture and moxibustion is getting higher and higher,especially the randomized controlled studies,and the number of trials with international standards is increasing.The standardized use of randomization,blind method,allocation hiding,and gold indicators has made the acupuncture and moxibustion trials recognized by international experts.It also provides a basis for western medicine to recommend acupuncture treatment and promotes the development of integrated traditional Chinese and Western medicine.In particular,the relevant trial and systematic evaluation published in 2021 have a very strong guiding role for clinicians'clinical decision making.To us in the essay concludes,acupuncture treatment of cancer-related symptoms,cardio-cerebrovascular disease,digestive system disease,joint disease,diabetes and other more substantial clinical evidence,such as south Korean scholars found that acupuncture often reduce the incidence of cardiovascular events in hypertensive patients,which further reflects the acupuncture treatment and prevention of the role as a whole.In foundation treatment,such as outstanding value,the study found the basis of the new champions league in COVID-19 treatment of acupuncture and moxibustion not only can play a role in anti-inflammatory and immune regulation,but also benefit patients with cancer and cardiovascular,which are consistent with researches conducted previously.We look forward to more discoveries to further explore the scientific value of this classic treatment.

Table 1 Evidence of acupuncture treatment of various diseases in 2021