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   Table of Contents - Current issue
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April-June 2021
Volume 7 | Issue 2
Page Nos. 155-286

Online since Monday, May 24, 2021

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REVIEW ARTICLES  

Current global status and future development of traditional Chinese medicine in the prevention and treatment of coronavirus disease 2019 Highly accessed article p. 155
Ze-Jia Song, Wan Najbah Nik Nabil, Zhi-Chao Xi, Hong-Xi Xu
DOI:10.4103/wjtcm.wjtcm_43_20  
Recognizing the potential of globalizing traditional Chinese medicine (TCM) for coronavirus disease 2019 (COVID-19), this review summarizes the current global use of TCM for COVID-19, status of the internationalization of TCM, and strategy on globalizing TCM for COVID-19. COVID-19 is a novel coronavirus disease that has sparked a pandemic in March 2020 affecting over 110 countries. Although researchers have been racing to develop targeted anti-COVID-19 treatment and vaccine, they are still currently unavailable. Thus, in treating patients infected with COVID-19, western medicine mainly recommended symptomatic treatment and monitoring. Existing drugs are used in the context of clinical trials, and the FDA still not yet approved these drugs for COVID-19. On the other hand, TCM proposed herbal treatment for suspected individuals to take within their observation period, as well as for confirmed COVID-19 patients to take during active phase of disease and during recovery. In China, Integrative Chinese-Western Medicine had been used in treating 91.5% of COVID-19 patients and showed its strength in reducing disease severity, shortening recovery time, and lowering the mortality rate. Despite obstacles in globalizing TCM for the treatment of COVID-19, promoting appropriate use of locally registered TCM products may prevent disease in susceptible individuals, improve the quality of life, and assist in the recovery of COVID-19 patients. With increasing global acceptance, TCM may play a more important role in the battle against infectious disease in the future.
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Progress of traditional chinese medicine treating COVID-19 p. 167
Ming-Xue Li, Yue-Ying Yang, Yang Liu, Meng-Zhu Zheng, Jun Li, Li-Xia Chen, Hua Li
DOI:10.4103/wjtcm.wjtcm_68_20  
The new coronavirus pneumonia (coronavirus disease 2019 [COVID-19]), caused by the new coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), mainly manifests by fever, dry cough, and fatigue. The emergence of SARS-CoV-2 poses a huge threat to people's lives. Unfortunately, so far, there are no effective treatment drugs and vaccines. Traditional Chinese medicine (TCM) has played an important role and achieved good results for treating this epidemic. More than 85% of patients with SARS-CoV-2 infection in China have received TCM treatment. In this article, we describe the progress of TCM for the COVID-19 therapy.
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ORIGINAL ARTICLES Top

Nrf2 activation by Morinda citrifolia L. (Noni) fruit juices p. 184
Arulmani Manavalan, Mallique Qader, Xiaohua Wu, Shugeng Cao
DOI:10.4103/wjtcm.wjtcm_24_21  
Objective: The objective of the study was to identify Nrf2 activators from differently treated Morinda citrifolia L. fruit juices and their cytotoxicity. Materials and Methods: Noni fruit juices were prepared by different treatments: unripe (T1), ripe (T2), purchased (T3), and Noni juices fermented with Lactobacillus plantarum (T4). These extracts were tested for Nrf2 activation and nuclear factor kappa B (NF-κB) inhibition activities. These active extracts were further studied for their nuclear Nrf2 translocation and induction of HO-1 protein expression. Finally, the active extracts were purified using open column chromatography and RP-high pressure liquid chromatography (HPLC) techniques through bioassay-guided separation. Moreover, all Noni juice samples were tested for cytotoxicity using mammalian cell-based methylthiazoltetrazolium (MTT) assay. Results: Only purchased (T3) and ripe Noni fruit juices fermented with LP at 22°C (T4–22) showed strongest Nrf2 activation and NF-κB inhibitory activity. Further, these two extracts enhanced the nuclear accumulation of Nrf2 after 2 h and also promoted Nrf2 and HO-1 nuclear translocation. Induction of HO-1 gene expression of Hep G2/ARE cells treated with T3 confirmed that it is a potent inducer of the Nrf2 target gene HO-1. Bioassay-guided separation resulted in subfractions with high Nrf2 activity. The strongest Nrf2 active subfraction led to the identification of scopoletin as an Nrf2 activator. Moreover, none of the tested samples showed any cytotoxicity for the MTT assay. Conclusions: The presence of potential Nrf2 activators in the Noni fruit juices that were nontoxic in our MTT assay could mitigate the production of harmful reactive species in the biological systems, and thereby, could helpful in alleviating and prevention of chronic diseases.
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Neuroprotective effects of San-Jia-Fu-Mai decoction: Studies on the in vitro and in vivo models of Parkinson's disease p. 192
Chang Qu, Ling Liu, Qing-Qing Xu, Yan-Fang Xian, Zhi-Xiu Lin
DOI:10.4103/wjtcm.wjtcm_62_20  
Objective: The objective of this study was to investigate whether 70% aqueous ethanol extract of San-Jia-Fu-Mai decoction extract (SJFMDE) could protect against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress in PC12 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor function deficits in mice. Materials and Methods: The cell viability, the levels of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) in the MPP+-treated PC12 cells were measured. Motor function deficits and dopamine (DA) level in the brain striatum and tyrosine hydroxylase (TH)-positive cells in substantia nigra pars compacta (SNc) of the MPTP-treated mice were determined. Results: The results showed that SJFMDE could reduce cell death and the levels of ROS and MDA while increase the level of GSH in the MPP+-treated PC12 cells. In addition, in vivo studies showed that oral administration of SJFMDE (3, 6, and 12 g/kg) significantly improved the motor function deficits induced by MPTP and enhanced the DA level in the striatum and TH-positive neuronal cells in SNc of the MPTP-treated mice. Conclusions: Our results revealed that SJFMDE possessed neuroprotective effects against neurotoxicity induced by MPP + and motor function deficits induced by MPTP via suppressing oxidative stress and increasing the levels of DA and TH, indicating that SJFMDE might be a promising Chinese medicine formula for the treatment of Parkinson's disease.
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An Exploration in the potential substance basis and mechanism of Chuanxiong Rhizoma and Angelicae Dahuricae Radix on analgesia based on network pharmacology and molecular docking p. 201
Ting-Ting Zhao, Rui-Rui Lan, Shang-Dong Liang, Günther Schmalzing, Hong-Wei Gao, Alexei Verkhratsky, Chuan-Hua He, Hong Nie
DOI:10.4103/wjtcm.wjtcm_81_20  
Objective: The objective was to study the potential substance basis and action mechanism of Chuanxiong Rhizoma (CX) and Angelicae Dahuricae Radix (AD) on analgesia through network pharmacology and molecular docking. Materials and Methods: The active components and targets of CX and AD and pain-related genes were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and GeneCards database. Then, the co-action targets were found, protein–protein interaction network was constructed by the String database. The Cytoscape 3.7.1 was used to construct “CX-AD-active components-pain” network. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was carried out to predict its mechanism of action, the top four active components in the network were docked with the targets. Results: There are 26 compounds, 45 targets in the network. Among them, (Z)-ligustilide and beta-sitosterol, respectively, have more potential targets in CX and AD, and prostaglandin-endoperoxide synthase (PTGS2), PTGS1 have more ligands. GO analysis shows that molecular functions of CX and AD mainly performed through the G protein-coupled amine receptor activity, adrenergic receptor activity, and catecholamine binding. KEGG analysis indicates that they could exert analgesic effect on the pathways of regulating neuroactive ligand-receptor interaction, serotonergic synapse, and cGMP-PKG signaling pathway. Molecular docking results show that the active compounds are highly compatible with the structure of the protein receptor, and they interact through the hydrogen bond and π–π bond between the ligand and the active site residues. Conclusions: Through network pharmacology and molecular docking, this study preliminarily revealed the main active components, targets, and potential regulation network of CX and AD, providing a reference for the subsequent experimental research.
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Garcinone E blocks autophagy through lysosomal functional destruction in ovarian cancer cells p. 209
Xiao-Huang Xu, Yu-Chi Chen, Yu-Lian Xu, Zhe-Ling Feng, Qian-Yu Liu, Xia Guo, Li-Gen Lin, Jin-Jian Lu
DOI:10.4103/wjtcm.wjtcm_83_20  
Background: High proliferative rate of cancer cells requires autophagy to maintain nutrient supply and intracellular homeostasis. As a result, impairing autophagic flux could be a novel strategy of cancer therapy. Aims and Objectives: In this study, the mechanism of a xanthone derivative isolated from Garcinia mangostana, garcinone E (GE), was investigated. Materials and Methods: Fluorescence assay was used to observe the accumulation and location of autophagosome and lysosome. Flow cytometry with Lyso-tracker red, MDC, and AO staining were applied to evaluate the lysosome accumulation and cellular acidity. Western blot and RT-qPCR were performed to evaluate the protein and mRNA levels, respectively. Results: GE could cause enhancement of LC3II and p62 and the accumulation of autophagosome and lysosome. Meanwhile, it limited the protein level of Rab7, increased lysosomal pH, and inhibited the maturation of lysosomal hydrolases such as Cathepsin L, therefore blockaded the fusion of autophagosome and lysosome. Moreover, GE acted as a TFEB modulator by downregulating its protein level, which might contribute to autophagy dysfunction in ovarian cancer cells. Conclusions: GE interfered autophagosome–lysosome fusion in cancer cells, which demonstrated its application as an autophagy regulator and a potential therapeutic agent.
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Safety assessment of Aconitum-Derived bulleyaconitine A: A 91-day oral toxicity study and a tissue accumulation study in rats p. 217
Shi-Liang Yin, Feng Xu, Hao Wu, Fei Li, Ge Jin, Zu-Qian Wu, Ran Meng, Si-Man Ma, Fan Zhou, Peter Breslin, Chun-Fu Wu, Hong Zhang
DOI:10.4103/wjtcm.wjtcm_77_20  
Background: Bulleyaconitine A (BLA) is a diterpenoid alkaloid from the rhizomes of Aconitum bulleyanum Diels and has been clinically used for chronic pain treatment in China for many years. However, the newly reported adverse events of BLA indicated that BLA still has potential safety issues. Materials and Methods: To assess the safety of BLA, analgesic tests, acute toxicity studies, repeated-dose oral toxicity studies, and tissue distribution studies after single and repeated administration of BLA were carried out. Results: Administration of 0.14 mg/kg BLA showed potent analgesic effects in both analgesic tests. In acute toxicity study, the LD50 value of BLA was calculated to be 3.4434 mg/kg. In the subchronic toxicity study, the no observed adverse effect level was 0.25 mg/kg, and the lowest observed adverse effect level was 0.5 mg/kg. The spleen, liver, and kidneys are newly identified target organs of BLA toxicity after long-term administration. Moreover, unlike a single BLA administration, repeated administration showed BLA redistribution from organs with an abundant blood supply to immune and metabolic organs. Conclusions: These results suggested that BLA itself would be nontoxic at a dosage of 0.25 mg/kg in rats and should be carefully used when combining BLA with medications that can cause spleen, liver, or kidney injury.
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Spectrum-toxicity correlation study revealed the influence of the nine-time steaming and sun drying method on hepatotoxic components of Polygoni Multiflori Radix p. 227
Zhuo Shi, Xiao-Fei Li, Ya-Lei Liu, Peng-Yan Li, Ming Niu, Zhao-Fang Bai, Guang-Qin Zhang, Yang Lu, Jia-Bo Wang
DOI:10.4103/wjtcm.wjtcm_2_21  
Objective: Polygoni Multiflori Radix (PM) is a traditional herbal medicine with repeated reports of liver injury events in recent years. We wondered whether the classical processing method, namely, nine-time steaming and sun drying (NSSD), had toxicity-attenuating effects on PM and the relationships between toxicity and times of processing, as well as with the alteration trends of its compounds. Materials and Methods: The chemical fingerprints of different PM extracts were developed using ultra-high-performance liquid chromatography. The spectrum-toxicity correlation between the chemical fingerprints and hepatocellular toxicity was analyzed with multiple correlation analysis. Results: The results suggested that the hepatotoxicity of NSSD processing products markedly decreased with the repeated steaming and sun drying, which was obviously superior to the product processed by the modern method. Comprehensive analysis revealed that the contents of cis-stilbene glycoside and emodin-8-O-β-D-glucoside related to liver injury susceptibility were reduced with the times of NSSD processing, which was consistent with the decreased trend of hepatocellular toxicity. After the five times of NSSD, the contents of them as well as the hepatotoxicity of PM were steady. Moreover, we found that the contents of catechin and physcion declined rapidly after the one time of NSSD and then remained stable until the nine times of NSSD. Based on the fact, they could be utilized to indicate whether PM products were processed by steaming and sun drying. Conclusions: This paper confirmed that the NSSD had a good influence on the toxicity attenuating to PM and found four compounds which could apply for the quality control of PM.
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Representation of specific diagnosis for low back pain using the 11th revision of international classification of diseases and related health problems: Perspectives of conventional medicine and traditional medicine p. 234
Anne Chang, Hong Zhao
DOI:10.4103/wjtcm.wjtcm_17_21  
Background: The 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11) was released on June 18, 2018, by the World Health Organization and will come into effect on January 1, 2022. Apart from the chapters on the classification of diseases in the conventional medicine (CM), a new chapter, traditional medicine (TM) conditions – Module 1, was added. Low back pain (LBP) is one of the common reasons for the physician visits. The classification codes for LBP in the ICD-11 are vital to documenting accurate clinical diagnoses. Methods: The qualitative case study method was adopted. The secondary use data for 100 patients were randomly selected using the ICD-11 online interface to find the classification codes for both the CM section and the TM Conditions – Module 1 (TM1) section for LBP diagnosis. Results: Of the 27 codes obtained from the CM section, six codes were not relevant to LBP, whereas the other 21 codes represented diagnoses of LBP and its related diseases or syndromes. In the TM1 section, six codes for different patterns and disorders represented the diagnoses for LBP from the TM perspective. Conclusion: This study indicates that specific diagnoses of LBP can be represented by the combination of CM classification codes and TM1 classification codes in the ICD-11; the CM codes represent specific and accurate clinical diagnoses for LBP, whereas the TM1 codes add more accuracy to the diagnoses of different patterns from the TM perspective.
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Determination of the bioaccessibility of cadmium in golden thread by physiologically based extraction test digestion using the in vitro/Caco2 cell model and subsequent risk assessment p. 240
Tian-Tian Zuo, Fei-Ya Luo, Hong-Yu Jin, Shu-Xia Xing, Bo Li, Kun-Zi Yu, Shuai Kang, Lei Sun, Shuang-Cheng Ma
DOI:10.4103/wjtcm.wjtcm_19_21  
Background: The ingestion of golden thread contaminated with heavy metals through the food chain leads to detrimental effects to human health. During digestion, not all of the heavy metals could be released to the gastrointestinal tract and readily to be absorbed by human body. Thus, bioaccessibility is an important issue in health risk assessments. Aims and Objectives: The aims and objectives of this study were to investigate the bioaccessibility of Cd in golden thread and assess the associated health risks based on the exposure to bioaccessible Cd. Materials and Methods: Inductively coupled plasma mass spectrometry (ICP-MS) has been applied to determine the Cd content in golden thread. Physiologically based extraction test (PBET) digestion was performed in the in vitro/Caco2 cell model to investigate the bioaccessibility of Cd in golden thread. Furthermore, the target hazard quotient (THQ) was used to assess the risks of the total and the bioaccessible content of Cd in golden thread. Results: The results revealed that the total Cd content in six batches of golden thread ranged from 3.203 to 5.723 mg/kg. After uptake by Caco2 cells, the bioaccessibility of Cd ranged from 42.36% to 59.73 %. The results of the risk assessment indicated that prior to uptake by Caco2 cells, the THQ values of Cd for all batches of golden thread were greater than 1. However, after uptake by Caco2 cells, the THQ values of Cd in all samples were less than 1, thus suggesting that the risks were at a safe level. Conclusion: This study was the first to perform health risk assessment with bioaccessible heavy metals present in traditional Chinese medicine by PBET digestion using an in vitro/Caco2 cell model, thus enabling us to obtain more accurate and objective results while allowing us to avoid unnecessary government intervention and to establish more reasonable limit standards for heavy metals.
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Pharmacokinetic and relative bioavailability of three secoiridoid glycosides in beagle dog plasma after oral administration of conventional and enteric-coated capsules of Gentianella acuta extract p. 246
Zhi-Bin Wang, Kai Li, Meng Wang, Gao-Song Wu, Yu-Jin Bi, Hai-Xue Kuang
DOI:10.4103/wjtcm.wjtcm_10_21  
Objective: To simultaneously investigate the pharmacokinetics of gentiopicroside, sweroside, and swertiamarin, which are constituents of Gentianella acuta, by developing and validating a simple, sensitive, and fast ultra-high-performance liquid chromatography–tandem mass spectrometry method. Materials and Methods: Blood samples were collected from the forward limb veins of six beagle dogs following oral gavage with G. acuta, the whole plant extract (39.90 mg/kg). Plasma samples were processed using liquid–liquid extraction. The analytes and paeoniflorin (internal standard [IS]) were separated using an Acquity® UPLC ethylene bridged hybrid amide column (2.1 mm × 100 mm, 1.7 μm) with isocratic elution using a mobile phase consisting of acetonitrile and 0.1% formic acid in water (80:20, v/v) at a flow rate of 0.4 mL/min. Quantification was performed using multiple reaction monitoring of the fragmentation transitions at m/z 401.1s594;179.0, 403.1→195.0, 419.1→179.0, and 525.2→449.1 for gentiopicroside, sweroside, swertiamarin, and the IS, respectively. Results: The linearity of the analytical response was good and the calibration curves were linear over concentration ranges of 1.20–192.0, 0.40–159.0, and 0.20–209.3 ng/mL for gentiopicroside, sweroside, and swertiamarin, respectively. The extraction recovery was in the range of 84.72%–91.34%, 84.58%–93.43%, and 82.75%–91.37% for gentiopicroside, sweroside, and swertiamarin, respectively. Conclusions: The method was successfully used to evaluate the pharmacokinetic parameters of gentiopicroside, sweroside, and swertiamarin in beagle dogs.
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Effect of moxibustion on cardiac remodeling and myocardial function in rats with exercise-induced fatigue p. 254
Zheng-Xian Shen, Jie Zhu, Yu-Lei Liang, Zhi-Fang Zhang
DOI:10.4103/wjtcm.wjtcm_70_20  
Objective: To explore the effect of moxibustion at Shenque(CV8) on myocardial structure and function in rats with exercise-induced fatigue. Methods: A 12-week treadmill training program was used to establish a rat model of exercise-induced fatigue. Fifty-six male SD rats removed six rats that did not reach the molding condition, Remaining rats were randomly divided into the following five groups: a normal group (n=10) that did not under go the exercise routine and were not treated, a control group (n=10) that did not under go the exercise routine, but received a mild dose of moxibustion at “Shenque” (CV 8) for 15 min, an untreated group (n=10) that received no treatment after exercise, a CV 8 group (n=10) that received a mild dose of moxibustion at “Shenque” (CV 8) for 15 min after exercise, a non-acupoint(tail) group(n=10) that received a mild dose of moxibustion at “non-acupoint” for 15 min after exercise. At one hour after the end of the 12-week training program, the left ventricular diastolic volume (LVDV), left ventricular systolic volume (LVSV), peak early diastolic mitral blood flow velocity (E), and peak late diastolic mitral blood flow velocity (A) were measured,and the E/A ratio were calculated. The serum myoglobin (Mb), creatine kinase-muscle/brain (CK-MB), and cardiac troponin-I (cTnI) levels were detected using an automatic biochemical analyzer. Results: When the values obtained before and after treatment were compared within the same groups, the LVDV, LVSV, E, and A were increased (P<0.05 or P<0.01), and the E/A were decreased (P<0.01) in the untreated group and the tail group. Regarding inter-group comparisons, the LVDV, LVSV, E, and A were increased (P<0.05 or P<0.01), and the E/A were decreased (P<0.01) in the untreated group and the tail group compared to the normal group and control group. Compared to the untreated group and the tail group, the LVDV, LVSV, E, and A were decreased (P<0.01) and the E/A were increased (P<0.01) in the CV 8 group. Compared to the normal group and the control group, the serum Mb, CK-MB, and cTnI levels were increased (P<0.01) in the untreated group and the tail group, and the serum Mb and CK-MB levels were also increased (P<0.01) in the CV 8 group. Compared to the untreated group and the tail group the serum Mb, CK-MB, and cTnI levels in the CV 8 group were decreased (P<0.01). Conclusions: Moxibustion at Shenque(CV8) can effectively prevent cardiac structural changes caused by exercise-induced fatigue and enhance heart function. This treatment does not have side effects in healthy rats and is a safe and effective technique..
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Severe acute respiratory syndrome coronavirus 2 virus-like particle and its application in Chinese medical research p. 258
Ruo-Dan Xu, Ming-Fei Shi, Jing Li, Ning Li
DOI:10.4103/wjtcm.wjtcm_55_20  
Background: The global outbreak of coronavirus disease 2019 (COVID-19) has brought disastrous consequences to public health and medical systems, whereas no approved medications are currently available. Benefits of traditional Chinese medicine (TCM) against COVID -19 have been observed, however, the underlying mechanistic actions remain unclarified. Due to high pathogenicity and infectivity of the new coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), the lack of access to SARS-CoV-2 and biosafety level 3 (P3) facilities has impeded scientific investigations of TCM against COVID-19. Though low-pathogenic coronavirus and pseudoviral systems have been applied to substitute SARS-CoV-2 in fundamental studies, both models cannot imitate virological and clinical features associated with SARS-CoV-2. The virus -like particle (VLP) is a virological model that is safe and could be performed without biosafety protections. Aims and Objectives: To construct VLP of SARS-CoV-2 containing structural proteins of authentic viruses and resembling the morphology, partial life cycle, and immunoreactions of natural virions, and to introduce VLP into Chinese medical research. Materials and Methods: Using mammalian expression system, we have currently constructed SARS-CoV-2 VLP containing four essential structural proteins. Results: Based on this model, we propose six aspects of research that could be carried out for TCM formulas in the fight against COVID-19. Conclusion: Application of the VLP model provides a safe methodology to strengthen the response systems of Chinese medicine in preventing and controlling newly identified infectious diseases and offers collaborative opportunities for interdisciplinary deciphering of molecular and biological basis of anti-viral TCM formulas.
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GUIDELINES Top

International clinical practice guideline of chinese medicine alzheimer p. 265

DOI:10.4103/wjtcm.wjtcm_28_21  
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International clinical practice guideline of chinese medicine climacteric syndrome p. 276

DOI:10.4103/wjtcm.wjtcm_85_20  
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International clinical practice guideline of chinese medicine anxiety p. 280
Qi-Sheng Tang
DOI:10.4103/wjtcm.wjtcm_29_21  
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