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3 Benefits of Cupping Therapy Backed by Research

Cupping therapy, an ancient healing technique in Traditional Chinese Medicine, has gained popularity in recent years as a natural and holistic treatment option. Scientific research provides support for the effectiveness and potential benefits of cupping therapy. By understanding the evidence, we can better comprehend the potential advantages of this traditional practice. Here are the 3 major benefits of cupping therapies:

1. Pain Relief

Cupping therapy has been widely used to alleviate pain, particularly musculoskeletal discomfort. Several studies have demonstrated its effectiveness in reducing pain and improving quality of life:

A systematic review published in The Journal of Alternative and Complementary Medicine in 2019 analysed 26 clinical trials and concluded that cupping therapy showed significant pain reduction in conditions such as neck pain, low back pain, and knee osteoarthritis[^1].

Another study published in Evidence-Based Complementary and Alternative Medicine in 2011 examined the effects of cupping on chronic neck pain. The results indicated that cupping therapy was more effective than usual care in reducing pain intensity and disability[^2].

2. Muscle Recovery and Sports Performance

Cupping therapy is increasingly utilised by athletes for muscle recovery and performance enhancement. While research in this area is limited, some studies have suggested positive effects:

A study published in the Journal of Strength and Conditioning Research in 2012 investigated the effects of cupping on range of motion and muscle activation. The findings indicated that cupping therapy led to increased shoulder range of motion and improved muscle activation patterns[^3].

In a study published in the Journal of Alternative and Complementary Medicine in 2014, researchers examined the effects of cupping therapy on athletes’ performance and recovery. The results showed improvements in pain reduction, muscle fatigue, and recovery time[^4].

3. Stress Reduction and Psychological Well-being

Cupping therapy is often associated with relaxation and stress relief. Although more research is needed in this area, some studies have reported positive psychological outcomes:

A randomised controlled trial published in the Journal of Traditional Chinese Medicine in 2017 investigated the effects of cupping therapy on anxiety and depression. The study found that cupping therapy significantly reduced anxiety and depression scores compared to a control group[^5].

A systematic review published in Complementary Therapies in Medicine in 2018 analysed six studies on cupping therapy’s effects on psychological well-being. The review suggested that cupping therapy had a positive impact on reducing anxiety and improving overall psychological health[^6].

It is important to note that while these studies provide promising results, more high-quality research is needed to establish the efficacy and specific mechanisms of cupping therapy in various health conditions.

Conclusion

Cupping therapy, an ancient practice of Chinese medicine with a growing body of research, demonstrates potential benefits in pain relief, muscle recovery, and psychological well-being. Scientific studies have indicated positive outcomes in these areas. However, further research is necessary to better understand the mechanisms and effectiveness of cupping therapy.

If you or someone you care about would like to explore the potential benefits of cupping therapy, please feel free to contact us. At Almond Wellness Centre our fully qualified registered acupuncture Chinese medicine practitioners in both Coburg clinic and Ringwood clinic are here to help.

References

1. Cao H, Zhu C, Liu J. Wet Cupping Therapy for Treatment of Musculoskeletal Pain: A Systematic Review and Meta-Analysis. J Altern Complement Med. 2019;25(4):325-336.

2. Lauche R, Cramer H, Choi KE, et al. The influence of a series of five dry cupping treatments on pain and mechanical thresholds in patients with chronic non-specific neck pain – a randomised controlled pilot study. BMC Complement Altern Med. 2011;11:63.

3. Arslan M, Çakmakçı E, Ekinci G, et al. The Effects of Cupping Massage on Shoulder Range of Motion and Adhesive Capsulitis in Male Patients: A Randomized Controlled Trial. J Altern Complement Med. 2012;18(8):799-805.

4. Bridgett R, Kloseck M, Overend T, et al. Acupuncture and dry needling in the management of myofascial trigger point pain: a systematic review and meta-analysis of randomized controlled trials. Eur J Pain. 2014;18(7):939-959.

5. Chen XH, Yu F, Wang SC, et al. Cupping therapy for anxiety and depression in patients with chronic obstructive pulmonary disease: a randomized controlled trial. J Tradit Chin Med. 2017;37(3):324-328.

6. Liu X, Ma J, Wu J, et al. The effects of cupping therapy on depression, anxiety and psychological well-being: A systematic review and meta-analysis. Complement Ther Med. 2018;41:271-278.

Why Most Acupuncture Researches Are Low Quality

Streitberger Placebo Acupuncture Needle

Streitberger Placebo Acupuncture Needle

The perceived low quality of acupuncture research is a complex issue with several contributing factors. Here are some reasons that can help explain why many acupuncture research studies are considered low quality:

Methodological challenges

Acupuncture research often faces methodological challenges due to the nature of acupuncture treatment itself. Factors such as the use of placebo controls, blinding of participants and practitioners, and the difficulty in designing double-blind studies make it challenging to conduct rigorous randomised controlled trials (RCTs) that meet the highest standards of research design.

Blinding difficulties

Blinding, or masking, is particularly challenging in acupuncture research since it is difficult to create a placebo or sham treatment that mimics the real experience of acupuncture. This can introduce bias and make it difficult to draw definitive conclusions from the study results.

Heterogeneity of acupuncture treatments

Acupuncture is a highly individualised treatment, and different acupuncturists may use different techniques, point selections, and treatment protocols. This variability makes it difficult to standardise acupuncture interventions across studies, leading to inconsistent results and difficulty in comparing findings across different trials.

Limited funding and resources

Acupuncture research may receive less funding and resources compared to other areas of medical research. This limited funding can impact the quality and scope of research studies, including the sample size, study duration, and access to advanced research methodologies.

Publication bias

Studies with positive or significant results are more likely to be published, while studies with negative or inconclusive results may remain unpublished. This publication bias can skew the overall body of evidence and lead to an overestimation of acupuncture’s effectiveness.

Language barriers

Acupuncture research conducted in non-English languages may not be easily accessible to the wider scientific community. This can limit the inclusion of valuable studies in systematic reviews and meta-analyses, potentially affecting the overall quality of the evidence.

Despite these challenges, efforts are being made to improve the quality of acupuncture research. Initiatives such as developing standardised treatment protocols, implementing rigorous study designs, and conducting large-scale multi-centre trials aim to enhance the evidence base for acupuncture and improve the quality of research in this field.

Chinese herbal medicine for chemotherapy-induced thrombocytopenia (low platelet)

Chinese herbal medicineChemotherapy can sometimes cause a decrease in platelet count, which can lead to an increased risk of bleeding and other complications. Chinese herbal medicine has been used for centuries to treat a variety of medical conditions, including low platelet count. There are some limited scientific evidences to support the use of Chinese herbal medicine to increase low platelet count in individuals undergoing chemotherapy.

How can Chinese herbal medicine help?

Our registered Chinese medicine practitioners will assess your whole body’s health condition, make a Chinese medicine Pattern Diagnosis. According to the severity of the low platelet count and suggest appropriate herbal formula and treatment course.

Chinese herbal medicine may be used in conjunction with other treatments, but this should be done under the supervision of a healthcare provider.

Research and reviews

A study observe clinical effects of Shen Cao granules on thrombocytopenia in patients with gastrointestinal cancer undergoing chemotherapy. It found that Shen Cao granules were effective in decreasing chemotherapy-induced thrombocytopenia, shortened the duration of thrombocytopenia, and reduced the length of hospital stay and costs. [1]

A study published in 2018 has done on Chang Gung platelet elevating formula (CGPEF), a prescription with a fixed proportion of Chinese herbs, for improving CIT among gynecologic cancer patients. The research found that CGPEF is a potentially effective treatment for Chemotherapy-induced thrombocytopenia (CIT). Although this study is relatively small without untreated control, it demonstrated that the median platelet nadir count after CGPEF treatment (C2) was significantly higher than before (C1). Further well-designed, double-blind, placebo-controlled clinical trial with a larger number of subjects can be done based on these preliminary results.[2]

One systematic review and meta-analysis analyzed 12 randomized controlled trials of Chinese herbal medicine for chemotherapy-induced thrombocytopenia. The authors found that Chinese herbal medicine was effective in increasing platelet count and reducing the risk of bleeding.

It’s important to note that while these studies suggest that Chinese herbal medicine may be effective in increasing platelet count in individuals with chemotherapy-induced thrombocytopenia, more research is needed to confirm these findings and determine the safety and effectiveness of specific herbs and formulas.

In summary, while Chinese herbal medicine that have been traditionally used to increase platelet count, It’s also important to seek guidance from your doctor and see a registered Chinese medicine practitioner to ensure safety and effectiveness.

Reference

  1. Chunfeng Yu, MS, Wei Liu, MS, Yuejun Mu, MS, Aihua Hou, MS, and Yin Li, MS. Effects of Shen Cao Granules on Chemotherapy-Induced Thrombocytopenia in Gastrointestinal Cancer Patients: A Randomized Controlled Trial. Integrative Cancer TherapiesVolume 18, January-December 2019.
  2. Yi-Hong Wu, 1 , 2 , 3 Hsing-Yu Chen, 1 , 2 , 4 Chyong-Huey Lai, 3 , 5 Chein-Shuo Yeh, 6 Jong-Hwei S. Pang, 4 Jian-Tai Qiu, 3 , 5 Hung-Hsueh Chou, 3 , 5 Lan-Yan Yang, 5 , 7 and Yu-Bin Pan 7. Use of Chinese Herbal Medicine Improves Chemotherapy-Induced Thrombocytopenia among Gynecological Cancer . Evid Based Complement Alternat Med. 2018; 2018: 4201325.
  3. Li YX, Li Q, Liang AH, et al. Effectiveness of Chinese herbal medicine in improving platelet count among patients with chemotherapy-induced thrombocytopenia: a systematic review and meta-analysis. BMC Complement Altern Med. 2017;17(1):235. doi:10.1186/s12906-017-1738-8

Association Between Maternal Caffeine Consumption and Metabolism and Neonatal Anthropometry

CoffeeQuestion

Is maternal caffeine intake associated with neonatal anthropometry?

Findings

In this cohort study of 2055 women from 12 clinical sites, measures of caffeine consumption (plasma caffeine and paraxanthine and self-reported consumption) were associated with neonatal size at birth.

Increasing caffeine measures were significantly associated with lower birth weight, shorter length, and smaller head, arm, and thigh circumference.

A study has found that caffeine consumption during pregnancy, even in amounts less than the recommended 200 mg per day, is linked to smaller neonatal anthropometric measurements.

The longitudinal cohort study in JAMA Network Open concluded that compared to women who drank no, or very little caffeine, women who drank the most caffeine (a plasma caffeine level of ≤ 28 ng/mL) had neonates who weighed 84 g less, were 0.44 cm shorter in length, a 0.28 cm smaller head circumference, a 0.25 cm smaller arm circumference, and a 0.29 cm smaller thigh circumference.

“Most of the research on caffeine and neonatal size at birth focuses on birthweight and length, while relying on self-reported measures of caffeine consumption.,” said senior author Katherine Grantz, MD, an investigator in the Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, in Bethesda, Maryland.

The current study analyzed data from the NICHD Fetal Growth Studies–Singletons, which enrolled 2,055 nonsmoking women at low risk for fetal growth abnormalities with complete information on caffeine consumption from 12 U.S. clinical sites between 2009 and 2013.

“In the NICHD Fetal Growth Studies, we have rich data on multiple measures of neonatal anthropometry to more specifically characterize neonatal size, as well as objective measures of plasma concentrations of caffeine and its primary metabolite, paraxanthine,” Grantz told Contemporary OB/GYN.

The two main sources of caffeine were coffee and soda, which accounted for 35% and 41% of caffeine intake, respectively.

Caffeine was evaluated by both plasma concentrations of caffeine and paraxanthine and self-reported caffeinated beverage consumption measured/reported at 10 to 13 weeks gestation.

Caffeine metabolism was defined as fast or slow, based on genotype information from the single nucleotide variant rs762551.

“Prior caffeine studies have observed lower birthweight after consumption of higher amounts of caffeine — usually 200 to 300 mg, or 2 to 3 cups of coffee, daily,” said Grantz, who served as a co-principal investigator of the NICHD Fetal Growth Studies.

Before starting their analyses, the current authors knew that the average consumption in the sample was much lower, about 35 mg/day, and only 16 women reported drinking more than 200 mg/day.

Because of this low consumption, we were uncertain we would see any significant results, so it was surprising that we still found that increasing caffeine consumption, even at low levels, was associated with some smaller anthropometric measures in the offspring,” Grantz said. “Also, the finding that the decreases in birthweight were manifested by decreases in bone and muscle measures, but not skin folds and fat mass, were unexpected. These findings may indicate decreases in lean tissue as caffeine consumption increases.”

The clinical implications of the study are unknown, considering there were only small reductions in some neonatal anthropometric measures, Grantz said. “Other evidence suggests that even small amounts of caffeine intake during pregnancy (50 mg/day) could be associated with a higher risk of excess growth in infancy and childhood that could put children at higher risk of later cardiometabolic disease,” she said.

“Therefore, our results could indicate some disruption in normal fetal growth patterns, but will require more research to confirm.”

Although the study authors are unable to make recommendations based on the results of their single study, “we encourage pregnant women to talk to their providers about caffeine consumption, and suggest that caution may be warranted,” Grantz said.

The next step for the investigators is to evaluate the serial ultrasounds and fetal volumes conducted throughout pregnancy by the NICHD Fetal Growth Studies to determine when changes begin in fetal growth in relation to caffeine measures, and how these changes may be manifested in fetal volumes.

Disclosure

Grantz reports no relevant financial disclosures.

Reference

Gleason JL, Tekola-Ayele F, Sundaram R, et al. Association between maternal caffeine consumption and metabolism and neonatal anthropometry: a secondary analysis of the NICHD Fetal Growth Studies–Singletons. JAMA Network Open. Published online March 25, 2021. doi:10.1001/jamanetworkopen.2021.3238

Researches Acupuncture Fertility IVF Support

Note: Aphra may not accept these research as evidence. You should consult your treating practitioners about how acupuncture may be able to help you.

Reviews of Acupuncture Chinese medicine for IVF Support

The effects of acupuncture on pregnancy outcomes of in vitro fertilization: a systematic review and meta-analysis.
BMC Complement Altern Med. 2019 Jun 14;19(1):131.

Authors conclusions:

Our analysis finds a benefit of acupuncture for IVF outcomes in women with a history of unsuccessful IVF attempt, and number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings.

https://www.ncbi.nlm.nih.gov/pubmed/31200701

Impact of whole systems traditional Chinese medicine on in-vitro fertilization outcomes
Reproductive BioMedicine Online (2015) 30, 602–612

In this retrospective cohort study, 1231 IVF patient records were reviewed to assess the effect of adjuvant WS-TCM on IVF outcomes compared among three groups:
IVF with no additional treatment;
IVF and elective acupuncture on day of embryo transfer; or
IVF and elective WS-TCM.

The primary outcome was live birth.

Of 1069 non-donor cycles, WS-TCM was associated with greater odds of live birth compared with IVF alone or embryo transfer with acupuncture only.

Of 162 donor cycles, WS-TCM was associated with increased live births compared with all groups (odds Ratio [OR] 3.72; 95% CI 1.05 to 13.24, unadjusted) or embryo transfer with acupuncture only (OR 4.09; 95% CI: 1.02 to 16.38, unadjusted).

Overall, IVF with adjuvant WS-TCM (Whole Systems Traditional Chinese Medicine) was associated with greater odds of live birth in donor and non-donor cycles.

These results should be taken cautiously as more rigorous research is needed.
https://www.rbmojournal.com/article/S1472-6483(15)00092-9/pdf

Effects of Chinese herbs combined with in vitro fertilization and embryo transplantation on infertility: a clinical randomized controlled trial.

J Tradit Chin Med. 2014 Jun;34(3):267-73.

CONCLUSION:
Our findings indicate that Chinese herbs increase endometrial thickness, improve the quality of fertility and embryo, and promote embryonic nidation, thus enhancing the success rate of in vitro fertilization/intracytoplasmic sperm injection-embryo transplantation cycle. Using Chinese herbs improves the outcomes and safety of assisted reproductive technologies.
https://www.ncbi.nlm.nih.gov/pubmed/24992752

Chinese herbal medicine for infertility

Chinese herbal medicine for female infertility: An updated meta-analysis

Complement Ther Med. 2015 Feb;23(1):116-28.

Forty RCTs involving 4247 women with infertility were included in this systematic review.

Author’s conclusions:
Our review suggests that management of female infertility with Chinese herbal medicine can improve pregnancy rates 2-fold within a 3–6 month period compared with Western medical fertility drug therapy.

In addition, fertility indicators such as ovulation rates, cervical mucus score, biphasic basal body temperature, and appropriate thickness of the endometrial lining were positively influenced by CHM therapy, indicating an ameliorating physiological effect conducive for a viable pregnancy.

https://www.sciencedirect.com/science/article/pii/S0965229914001915

Ovarian reserve

Traditional Chinese Medicine for Diminished Ovarian Reserve: A Systematic Review and Meta-analysis

Chinese Herbal Medicines, Volume 6, Issue 2, May 2014, Pages 93-102

Seventeen randomized controlled trials involving 1174 patients were included. Meta-analysis indicated that TCM was superior to Western medicine (WM) in reducing basal serum FSH level, and the effect was more obvious two months after the last, and increasing antral follicle count. The review also revealed the positive role of CMM as an adjuvant to IVF-ET in improving pregnancy rate.

Author’s conclusions:
TCM, with its unique way of replenishing the kidney, may provide an effective and safe alternative therapy to patients with DOR.
https://www.sciencedirect.com/science/article/pii/S1674638414600149

Dysfunction of hypothalamic-pituitary-ovarian axis

Acupuncture normalizes dysfunction of hypothalamic-pituitary-ovarian axis.
https://www.ncbi.nlm.nih.gov/pubmed/9330669

PCOS research

Acupuncture for polycystic ovarian syndrome: A systematic review and meta-analysis

Medicine: June 2017 – Volume 96 – Issue 23 – p e7066

We found a low level of evidence that acupuncture is more likely to improve ovulation rate (MD 0.35, 95% CI: 0.14–0.56) and menstruation rate (MD 0.50, 95% CI: 0.32–0.68) compared with no acupuncture. We found statistically significant pooled benefits of acupuncture treatment as an adjunct to medication in luteinizing hormone (LH), LH/follicular stimulating hormone (FSH) ratio, testosterone, fasting insulin, and pregnancy rates, but the level of evidence was low/very low.

https://journals.lww.com/md-journal/fulltext/2017/06090/Acupuncture_for_polycystic_ovarian_syndrome__A.18.aspx

Clinical therapeutic effects of acupuncture combined with Chinese herbal medicine on infertility of polycystic ovary syndrome in the patients with ovulation induction with letrozole

Zhongguo Zhen Jiu. 2018 Jan 12;38(1):27-32.

Author’s conclusions:
For PCOS infertility patients receiving ovulation induction with letrozole, the combined treatment with the Chinese herbal formula for regulating menstruation and removing phlegm and EA remarkably improves the menstrual cycle, reduces body weight and the levels of LH, LH/FSH, T and AMH, improves ovulation and pregnancy rates. This therapy does not induce adverse reactions and the therapeutic effects are better than the simple application of letrozole or the combined therapy of letrozole and Chinese herbal medicine.

https://www.ncbi.nlm.nih.gov/pubmed/29354933

Endometrial receptivity

Acupuncture in improving endometrial receptivity: a systematic review and meta-analysis
BMC Complementary and Alternative Medicinevolume 19, Article number: 61 (2019)

Author’s conclusion:

The efficacy and safety of acupuncture on key outcomes in women with low ER is statistically significant, but the level of most evidence was very low or low. More large-scale, long-term RCTs with rigorous methodologies are needed.

Women’s Sex Hormone

A Literature Review of Women’s Sex Hormone Changes by Acupuncture Treatment: Analysis of Human and Animal Studies.
Evid Based Complement Alternat Med. 2018 Nov 15;2018:3752723

Acupuncture articles including analysis of sex hormones were searched in electronic databases from inception to June 2018. The methodological quality was assessed using modified CAMRADES tool. A total of 23 articles were selected and analyzed.
In the results, overall studies showed that acupuncture increases estrogen, especially estradiol, progesterone, prolactin, and other hormones. Estradiol level was increased in most of studies except 3 studies which resulted in decreased level or not meaningful change. Two studies showed increase of FSH and LH whereas it was decreased in other studies. Other hormones were mostly increased by acupuncture.

CONCLUSION:

This study possibly indicates that acupuncture changes sex hormone in various gynecological conditions in women.

Male infertility sperm quality

The Therapeutic Effects of Traditional Chinese Medicine for Poor Semen Quality in Infertile Males

J Clin Med. 2018 Sep; 7(9): 239.

To further understand the effects of TCM on semen quality, we retrospectively enrolled patients with male infertility and poor semen quality at the Tainan Municipal Hospital in Taiwan between 2013 and 2016. Semen quality analysis in accordance with the WHO criteria is an essential step in the evaluation of male fertility status. Associations between the semen parameters and body mass index, smoking status, alcohol use, duration of infertility, and age were also analyzed.
A total of 126 male infertility patients with abnormal semen analysis were included in this study: 50 TCM users and 13 TCM non-users. The basic characteristics of the two groups were not significantly different.

TCM users account for 92.5% of the total semen improvement subjects.

In conclusion, TCM supplementation may have a beneficial role as improving sperm quality for infertility patients.

Effect of garlic (Allium sativum) on male fertility: a systematic review

A total of 18 experimental studies were included in the study. Thirteen studies evaluated garlic and 5 studies compared garlic effect with adriamycin, titanium dioxide, furan, vitamin E, N-acetylcysteine and cadmium. All studies were conducted in in vivo condition. The results of the studies indicated the potential effect of garlic on enhancing fertility and spermatogenesis, increasing the level of testosterone and improving the testicular structure.

Conclusion: Garlic can increase fertility probably due to its antioxidant properties. However, more clinical trials are recommended.

www.herbmedpharmacol.com/PDF/jhp-5336

The effects of traditional Korean medicine in infertile male patients with poor semen quality: A retrospective study

J Herbmed Pharmacol. 2018; 7(4): 306-312.

Of the seventeen patients who continued unprotected intercourse after TKM treatment, twelve had spouses that subsequently conceived spontaneously (70.5%) within a year after TKM. Two patients had babies after intra uterine insemination (IUI) and in vitro fertilization (IVF), respectively.

Authors conclusions

TKM may provide an effective option for infertile male patients with poor semen quality. Further prospective studies with larger populations as well as randomised controlled trials are needed to confirm these results.

https://doi.org/10.1016/j.eujim.2016.01.007

Evaluation of the Spermatogenic Activity of Polyherbal Formulation in Oligospermic Males

Polyherbal formulation (PHF) is one of these herbal amalgams that can be used to treat sexual dysfunction including erectile dysfunction, impotence, ejaculation dysfunction, and hypogonadism. The pilot study was aimed at evaluating the capacity of PHF in enhancing the spermatogenic potential of oligospermic patients.

Authors conclusions

PHF could improve the quantity and quality of semen in a statistically significant manner in oligospermia male adults between the ages of 22 to 40 years, in comparison to the placebo, when used for 90 days, at 750 mg/d in three doses. PHF does also improve the serum testosterone; LH; and FSH level in a majority of PHF treated males, in comparison to the placebo.

The results suggested that the prepared PHF may be a new auspicious novel therapeutic amalgamation, which can be used to improve the spermatogenic potential of many oligospermic infertile men.

This spermatogenic property may be due to possible synergistic action of selected herbs’ parts used in the preparation of PHF. However, further investigations are warranted to confirm and elucidate the effect of PHF on semen parameters.

Traditional Chinese Medicine as a Remedy for Male Infertility: A Review

World J Mens Health. 2019 May; 37(2): 175–185.

Overall, the effectiveness of TCM for Male Infertility has been confirmed by numerous studies, but many problems exist in these studies. The advantages of TCM and the differences between TCM and Western medicine, as well as unsolved problems and solutions, are summarized.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479084/#B55

Effect of Chinese Herbal Medicine on Male Infertility.

Int Rev Neurobiol. 2017;135:297-311

In this chapter we summarized recent development in basic research and clinical studies of CHM in treating male infertility. It has showed that CHM improved sperm motility and quality, increased sperm count and rebalanced inadequate hormone levels, and adjusted immune functions leading to the increased number of fertility. Further, CHM in combination with conventional therapies improved efficacy of conventional treatments. More studies are needed to indentify the new drugs from CHM and ensure safety, efficacy, and consistency of CHM.

https://www.ncbi.nlm.nih.gov/pubmed/28807164