Friday, 6 December 2024

Comments on Chinese Medicine Research Papers Published in The Lancet

 Tiejun Tang    

A recent research paper published in the internationally renowned medical journal The Lancet titled "Traditional Chinese Medicine FYTF-919 (Zhongfeng Xingnao Oral Prescription) for the Treatment of Acute Cerebral Hemorrhage: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Clinical Trial" [1] concluded that the efficacy of the traditional Chinese medicine (TCM) prescription, Zhongfeng Xingnao Oral Prescription, was no different from that of a placebo, and it could not improve the functional prognosis, survival rate, or quality of life of patients with cerebral hemorrhage. This conclusion could easily mislead readers into thinking that traditional Chinese medicine is ineffective in treating cerebral hemorrhage, causing a negative impact on the reputation of TCM and provoking strong responses from the TCM community both domestically and internationally.

But is it really true that traditional Chinese medicine is ineffective in treating cerebral hemorrhage? No! The conclusions of this study only show that the specific prescription used in the trial is ineffective, and they cannot be generalized to all traditional Chinese medicines. The main issue with the negative research results lies in the selection of the prescription.

Zhongfeng Xingnao Oral Prescription contains four ingredients: Hongshen, Sanqi, Chuanxiong, and Dahuang. My opinion is using Chuanxiong in the treatment of acute cerebral hemorrhage is fundamentally incorrect.

The Chinese Pharmacopoeia records that Chuanxiong is pungent, warm, and acts on the liver, gallbladder, and pericardium meridians. It is known for promoting blood circulation, dispelling wind, and relieving pain. It is typically used for irregular menstruation, dysmenorrhea, abdominal pain due to lumps, stabbing chest and rib pain, swelling and pain from injuries, and headaches. In clinical practice, Chuanxiong is recognized for its ability to promote blood circulation and remove blood stasis, making it an important medicine for treating headaches. Modern pharmacological studies have confirmed that the main active ingredient of Chuanxiong is ligustrazine. The pharmacological effects of Chuanxiong and ligustrazine have been hotly researched, with over 1,000 articles available on PubMed when searching for "Chuanxiong" or "ligustrazine" (1022 and 1608 papers, respectively). In 2024 lone, there were 96 and 115 studies published on the topic.

Recent studies on Chuanxiong’s effect on coagulation and blood rheology reveal some concerning findings:

  1. One study using network pharmacology found that Chuanxiong can inhibit TF (tissue factor) procoagulant activity and reduce TF mRNA and protein expression in EA.hy926 cells in a dose-dependent manner via the PI3K/Akt/NF-κB signaling pathway [2].
  2. Another study using affinity ultrafiltration mass spectrometry (AUF-MS) identified 21 active components from Chuanxiong, with ferulic acid, chlorogenic acid, and isochlorogenic acid A being potential antithrombin agents. The conclusion was that Chuanxiong is a Chinese herbal medicine with good anticoagulant effects [3].
  3. A third study using a microfluidic chip model of normal and stenotic arteries showed that ligustrazine inhibits platelet aggregation and activation by reducing the binding of von Willebrand factor (vWF) to the GPIb/IX/V complex, partly inhibiting platelet aggregation through the P2Y12-ADP receptor pathway [4].

Ligustrazine has effects such as inhibiting platelet aggregation, dilating blood vessels, reducing blood viscosity, and anticoagulation. It is mainly used in the treatment of ischemic stroke and can be employed for rehabilitation in hemorrhagic stroke. However, it is obviously unsuitable for use in the acute stage of cerebral hemorrhage, as its anticoagulant properties could worsen bleeding.

In contrast, Western medicine uses hemostatic drugs such as aprotinin, 6-aminocaproic acid, and tranexamic acid in treating acute cerebral hemorrhage to correct coagulation dysfunction and prevent the expansion of the bleeding area. Although the clinical effect of hemostatic drugs is not ideal, they remain one of the routine treatments for acute cerebral hemorrhage. The effect of ligustrazine on coagulation is completely opposite to that of hemostatic agents.

Traditional Chinese medicine (TCM) holds that "blood that leaves the vessel is stagnant," and there are indeed reports of using blood-activating and blood-stasis-removing methods to treat cerebral hemorrhage. However, this is generally applied in the recovery period, not in the acute phase. TCM often uses Sanqi (Panax notoginseng), which has both blood-activating and hemostatic effects, in such treatments. The two ingredients, Chuanxiong and Dahuang, in this particular prescription both promote blood circulation, which does not align with the TCM principles of syndrome differentiation and treatment. This discrepancy likely led to the negative research results in the study.

For treating acute cerebral hemorrhage, TCM must follow the principle of syndrome differentiation. For example:

  • Angong Niuhuang Wan clears heat, resolves phlegm, and opens the orifices, suitable for phlegm-heat blocking type stroke.
  • Shenfu Tang is used for yang qi exhaustion syndrome.
  • Shengmai San is used for qi and yin deficiency syndrome.

There is no single prescription that can effectively treat all types of strokes.

Furthermore, scientific research on TCM must respect the inherent principles of TCM. It cannot simply replicate the Western medical research model, as this approach would lead to biased conclusions.

References:

  1. Jianwen Guo. Traditional Chinese Medicine FYTF-919 (Zhongfeng Xingnao Oral Prescription) for the Treatment of Acute Intracerebral Hemorrhage: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Clinical Trial. The Lancet, 2024 Nov; Volume 404, Issue 10468, Pages 2187-2196.
  2. Shasha He. "Exploring the Mechanism of Chuanxiong Rhizoma Against Thrombosis Based on Network Pharmacology, Molecular Docking and Experimental Verification." Molecules, 2023 Sep 19; 28(18): 6702.
  3. Chencun Huang. "Screening of Anti-Thrombin Active Components from Ligusticum Chuanxiong by Affinity-Ultrafiltration Coupled with HPLC-Q-Orbitrap-MS." Phytochemical Analysis, 2023 Jun; 34(4): 443-452.
  4. Tiancong Zhang. "Application of Microfluidic Chip Technology to Study the Inhibitory Effect of Tetramethylpyrazine on Platelet Aggregation, Activation, and Phosphatidylserine Exposure Mediated by Pathological High Shear Rate." Blood Coagul Fibrinolysis, 2023 Jan 1; 34(1): 47-60.


Thursday, 6 June 2024

The best reward for my 40 years clinical practice

Tiejun Tang

This year marks the 40th anniversary of my graduation from the University of Traditional Chinese Medicine, which marked the beginning of my career as a TCM doctor and university teacher. 

An International Chinese media and an authoritative academic institution selected 22 The Overseas Grand Master of Traditional Chinese Medicine and 155 Famous Practitioner of Traditional Chinese Medicine in the world. I am very honored to be selected as one of the 22 Overseas Grand Master of Traditional Chinese Medicine. This is the best reward for my 40 years career.

The certificate of the Overseas Grand Master of Traditional Chinese Medicine was received. I would like to thank the selection committee for their excellent work. Unfortunately, due to the time arrangement, I was unable to attend the awards ceremony in Vancouver today. I wish the conference had successfully accomplished.

At this moment, I would like to say a few words to express my feelings from the bottom of my heart:

First of all, I would like to thank my teachers in the past 45 years since I had entered the world of Traditional Chinese Medicine, including all of my teachers in my undergraduate, MSc, PhD and post-doctoral research stages. I would like to thank every alma mater where I studied and worked together for the past years.

Also, I would like to thank the countless of patients that I had treated in China and the UK in the past 40 years. Your suffering is my motivation to keep making progress. Practitioners' knowledge comes from learning, but most of their clinical experience comes from patients’ feedback

I would like to thank my students who based in China, UK and Europe in the past 40 years. Teaching and learning always enhances each other. Being a good teacher and leading my students on the right path is an additional motivating force to continue my journey.

I would like to thank my classmates, colleagues, and friends at all stages who have supported and helped me over the years. 

At last, I would like to thank my family and relatives who have given me a great support all along.

I’m so grateful to have you all in my life.

Monday, 15 April 2024

Precancerous lesions and complementary medicine approach

 TiejunTang 

In recent years, we have often heard bad news about someone who suffers from any type of cancer. According to the statistics of the Cancer Research UK, there are around 375,000 new cancer cases in the UK every year (2016-2018), and around 167,000 cancer deaths in the UK every year (2017-2019). World Cancer Research Fund reported there were 18.1 million cases of cancer diagnosed in 2020 globally.

The prognosis of different cancers are various. Some are completely curable due to the development of medical science; unfortunately some are not. Although they are incurable, we can prevent it. Cancers take time to develop; they often develop from some chronic diseases. These diseases are often called precancerous lesions. If you are being treated appropriately, the condition could be under control.

Below are some examples of common precancerous lesions and the effectiveness of Chinese herbal medicine in these conditions.

1. Atypical Breast Hyperplasia Breast Cancer

Breast cancer is one of the most common cancers, and it often develops from inconspicuous precancerous lesions, such as breast atypical hyperplasia, intraductal papilloma and cystic breast hyperplasia, which are all considered to be precancerous lesions.

From the perspective of traditional Chinese medicine (TCM) , breast hyperplasia is a condition that causes by stagnation of liver qi, which leads to the blockage of qi in the body, resulting in breast pain. TCM herbs that soothe the liver and relieve stagnation can be given to intervene. Commonly used herbs are Xiangfu, Qingpi and Chenpi for soothing the liver and regulating qi. Chishaoyao can be added to activate blood circulation and remove blood stasis, Gualou can be added to resolve phlegm and dissipate stagnation, and Banzhilian & Baihuasheshecao can be added for anti-cancer, as well as reducing the risks of getting breast cancer.

A molecular level experimental study showed: The Chinese herbs Huangqi, Renshen, Fuling and Chaihu, as well as some other herbal formulas can regulate the genetic related and protein expression via pathways such as PI3K/AKT/mTOR, MAPK and Wnt/β-catenin, which inhibits the growth, proliferation, migration, invasion and metastasis of triple-negative breast cancer cell.[1]

2. HPV Infection Cervical Cancer

HPV (human papillomavirus), is divided into high-risk, intermediate-risk and low-risk types according to the risk of causing cervical cancer. Among them, 13 types of viruses are considered in the high-risk category. In the worldwide, there are 90% of cervical cancers are caused by HPV.  In the Western medicine, there isn’t any specific medication for treating HPV, however, It can only be relied on our immunity to cure the disease. In some cases, most of the infections can be healed by themselves within 2 years, however, some patients are potentially suffering from the cervical cancer in the end.

Traditional Chinese Medicine (TCM) believes that this disease is mostly caused by damp-heat, spleen-deficiency, endogenous dampness, as well as toxins which are one of the primary pathologies. Treatment is usually based on strengthening the spleen and removing dampness, clearing away the heat and detoxifying.  The modified formula of the Traditional Chinese medicine, the Simiao Decoction is used in the treatment of HPV, showing the satisfactory efficacy.

The Research shows that the mechanism of Chinese herbal medicine may perform on the regulation of cell apoptosis, viral gene transcription and translation, cell signal transduction pathways and the immune function.[2]

3. Colon Polyps Colon Cancer

Colon cancer is relatively one of the common cancers in the UK, and a large proportion of colon cancers develop from the polyps. Adenomatous polyps have a higher probability of becoming cancerous.  As the size of adenomatous polyps grows, their growth rate is also increased with the total canceration rate ranging from 10% to 20%, therefore, the Western medicine uses endoscopic electrocoagulation resection for the treatment of intestinal polyps, and the recurrence rate is very high.

TCM believes that the causes of colon polyps is due to damp heat, phlegm, and blood stasis that accumulate in the large intestine. The principles of treating this disease are to strengthening the spleen and replenishing the qi, clear away damp heat, and resolve phlegm and blood stasis. In my master degree research in the early 1990s, I applied Jianpi Yikan Pills to treat the intestinal polyps and a satisfactory result was achieved. This patent remedy can be significantly reduced the postoperative recurrence of intestinal polyps.[3]

4. Chronic Atrophic Gastritis Stomach Cancer

For chronic stomachache patient, a gastroscopy is necessary. If the biopsy result of the gastroscopy is chronic atrophic gastritis, We must pay more attention to it, especially if it is accompanied by atypical hyperplasia and intestinal metaplasia, a high risk of stomach cancer is associated.  It is generally believed that the canceration rate is: 3% to 5% in 5 to 10 years, and 10% in more than 10 years. 

TCM believes that the etiology and pathology of atrophic gastritis may include liver and stomach qi stagnation, spleen and stomach deficiency, stomach-yin deficiency or stomach blood stasis. The herb selection should depend on the symptoms of individual cases: Chaihu, Foshou to soothe the liver and relieve the liver qi stagnation ; Dangshen and Baizhu to strengthen the spleen and stomach Qi; Maimendong, Shashen and Shihu to nourish stomach yin;  Chishaoyao and Danshen to remove blood stasis.

Research shows that the mechanism of TCM in treating chronic gastritis include the eradication of Helicobacter pylori, the anti-inflammatory effects, the immune regulation, and the regulation of gastric mucosal cell proliferation, apoptosis, and autophagy levels[4].

5. Pulmonary Nodules Lung Cancer

Chronic cough has increased since the pandemic of COVID-19.  Many people were diagnosed with pulmonary nodules after Covid.  This disease may lead to lung cancer, among which atypical adenomatous hyperplasia which is a type of precancerous lesion.  The bigger the nodule, the higher risk of malignant transformation. People with lung cancer family history are more likely to develop cancer in their lung nodules.

Nevertheless, there is no evidence that pulmonary nodules can be treated by any western medicines, and the surgical operation is necessary for the larger nodules, although the new nodules may reoccur after the surgery.

TCM believes that the main pathogenesis of pulmonary nodules is: deficiency, phlegm, blood stasis, and poison. The treatment principles are to nourish the spleen and lungs, resolve phlegm and detoxify, and dissipate blood stasis and dredge the collaterals.

Usually, Huangqi and Dangshen are used to replenish the qi of the spleen and lungs; Banxia, Qianhu, Zhebeimu and Gualou are used to resolve phlegm and relieve cough, Banzhilian and Yuxingcao are used to clear away heat and detoxify; Sanqi and Danshen are used to activate blood circulation and remove blood stasis.

The Molecular biology and pharmacology research shows that the traditional formula, QianJin WeiJing decoction (QJWJ) can inhibit the growth of lung cancer A549 cell line in a time-dependent manner, which may inhibit the growth of lung cancer cells by inhibiting EGFR and STAT3 signaling pathways, and arresting the cell cycle in G0/G1 phase. The other research showed QJWJ can induce apoptosis in lung cancer cells and enhancing immunity in lung cancer patients. [5]

6. Cirrhosis Liver Cancer

Viral hepatitis is a very common disease in China. In about 10-30% of chronic hepatitis B patients develop cirrhosis within 5-10 years, besides, 5-10% of cirrhosis patients develop liver cancer within 5-10 years as well.  Cirrhosis is considered as a precursor to liver cancer. Although viral hepatitis is relatively rare in the UK, alcoholic cirrhosis becomes the risk factor of liver cancer.

TCM has accumulated immeasurable clinical experiences in treating chronic liver diseases over thousands of years. For those with hypochondriac pain and swelling pain, Chaihu, Qingpi, and Chunlianzi can be used to promote qi and relieve pain; for jaundice conditions, Yinchen, Dahuang and Zhizi can be selected to clear away damp heat and relieve jaundice; for ascites conditions, Fuling, Zexie, Dafupi can be added to diuretic and expel dampness; for patients with hepatosplenomegaly, Danshen, Sanleng, Ezhu can be given to promote the blood circulation and remove blood stasis, or Guiban and Biejia can be used to soften the hardness; for those with cancer tendencies, Banzhilian and Baihuasheshecao can be added to prevent the occurrence of tumors.

There was a cohort study that counted 127,237 liver cancer patients, of which 30,992 (24.36%) were treated with Chinese herbal medicine. Compared with patients who did not use Chinese herbal medicine, The TCM group showed a significantly lower risk of deathModified Xiaoyao San and Chaihu Shugan San were the most effective formulas for improving survival.  [6]

Most importantly, getting early diagnosis and treatment are the most crucial part, as it has a great impact on the patient’s prognosis.

Paying enough attention to the treatment of precancerous lesions can slow down or stop the canceration of cells and avoid the occurrence of cancer. Clinical practice has proven that traditional Chinese medicine can have advantages to the treatments listed above dedicated to precancerous lesions, and its mechanism of action has been confirmed by a variety of scientific studies.

Be aware of the precancerous lesions and eliminate potential risks of cancer is the right choice of your health.

Reference:

1. Zimei Yang. The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer. J Ethnopharmacol. 2021 Jan 10:264:113249.

2. Jing Lin. Traditional Chinese medicine for human papillomavirus (HPV) infections: A systematic reviewBiosci Trends. 2017 Jul 24;11(3):267-273.

3. Tiejun Tang. The effect of JPYK pill on T cell subpopulation and immunological function of spleen asthenia mice. Pharmacology and Clinics of Chinese Materia Medica. 1992; 8 (Sep.): 181.

4. Liangjun Yang. Progress in traditional Chinese medicine against chronic gastritis: From chronic non-atrophic gastritis to gastric precancerous lesions Heliyon.2023 May 27;9(6):e16764

5. Peiyu Liu. A Chinese classical prescription QianjinweijingDecoction in treatment of lung cancer: An overview. Biomed Pharmacother. 2022 Dec:156:113913

6. Yueh-Hsiang Liao. Adjunctive traditional Chinese medicine therapy improves survival of liver cancer patients. Liver Int. 2015 Dec;35(12):2595-602.



Tuesday, 2 April 2024

Comments on the red yeast incident in Japan

 Tiejun Tang

Recently, there are many people in Japan have been hospitalized or even died due to kidney disease after taking health products containing red yeast rice which produced by Kobayashi Pharmaceutical Company. As of the evening of the 28th March 2024, there were 5 people died and 114 were hospitalized because of the products. It aroused a great attention in Japan and also, many people were alarmed by the incidents, as well as the safety of how to consume the health care products appropriately.

Red yeast rice have been consuming as food and medicine in China for nearly 700 years. In one of the classic books regarding the food and nutrition - "Yin Shan Zheng Yao", which was published in 1330, was stated that this product had the effects of strengthening the spleen, replenishing qi, and warming the stomach at the time.  Li Shizhen, a famous Chinese herbalist in the Ming Dynasty, the author of "Compendium of Materia Medica" also mentioned that red yeast rice had the same beneficial effects.

In 1979, a Japanese scholar Akira Endo isolated Monacolin K from red yeast rice. In 1985, an American scientists Goldstein and Brown further proposed the mechanism of action of Monacolin K in inhibiting cholesterol synthesis, and thus obtained Nobel Prize, therefore, Monacolin K is regards as the first inventor of statins.

Lowering cholesterol is one of the advantages of taking Statin, but for long-term, it shows some side effects.[1] According to the results of many pharmacological studies and randomized controlled clinical trials showed that red yeast rice has lipid-lowering effects similar to those of statins[2-4],  as a natural statin drug, it is relatively safer and is widely used in the treatment of hyperlipidemia in China and Japan.

In traditional Chinese medicine, red yeast often combine with Shanzha (Hawthorn) and  Zexie (Alismatis Rhizoma) and other ingredients that have the similar effect of lowering blood lipids compared with Statin. They are not only lower cholesterol but also reduce triglycerides and balance lipoprotein metabolism.  A research report showed that Chinese herbal medicine, Shanzha have better function in reducing low-density lipoprotein cholesterol (LDL-C) compare to Simvastatin. [5] A molecular biology and network pharmacology study showed that Zexie decoction can decrease total cholesterol (TC), Triglycerides (TG) and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo.[6]

Why was these incidents happened in Japan?  As Red Yeast Rice has always been considered as a safe and healthy food product.  The current investigation believes that it was due to an error in the process of fermentation during the production, the harmpful substances were in the same batch of the production which caused the people got poisoned accidentially.  The specific investigation results are yet to be determined. The further announcements are to be expecting until further investigations.

Such incident was traumatised, and people would become panicked and worried, however, this incident reminds all pharmaceutical companies that GMP standards and the quality control should be strictly followed.  Moreover, the advantages of using Red Yeast Rice for the treatment of hyperlipidemia as a natural medicine is still valuable.

Reference: 

1.      Natalie C Ward.  Statin Toxicity Circ Res. 2019 Jan 18;124(2):328-350.

2.      Cicero AFG  Red Yeast Rice for Hypercholesterolemia. Methodist Debakey Cardiovasc J. 2019 Jul-Sep;15(3):192-199.

3.      Takuya Minamizuka . Low dose red yeast rice with monacolin K lowers LDL cholesterol and blood pressure in Japanese with mild dyslipidemia: A multicenter, randomized trial. Asia Pac J Clin Nutr2021 Sep;30(3):424-435.

4.      Peng D, Original Research: The Effects of Red Yeast Rice Supplementation on Cholesterol Levels in Adults..Am J Nurs. 2017 Aug;117(8):46-54.

5.      Hong Xu. A study of the comparative effects of hawthorn fruit compound and simvastatin on lowering blood lipid levels. Am J Chin Med . 2009;37(5):903-8.

6.      Zhishen Xie. Zexie Tang targeting FKBP38/mTOR/SREBPs pathway improves hyperlipidemia J Ethnopharmacol. 2022 May 23:290:115101