Application of clinical value assessment of treatment protocols in guideline development: taking the WFAS Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine as an example. / 治疗方案临床价值评估在指南制定中的应用.

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.

Effectiveness of Acupuncture for Prophylactic Treatment of Migraine: A Systematic Review and Bayesian Network Meta-Analysis.

It is aimed to evaluate the effectiveness and provide evidence-based medical support for acupuncture as a prophylactic treatment for migraines. Randomized controlled trials (RCTs) from inception to April 2022 are included in 14 databases. Pairwise meta-analysis is conducted using STATA software V14.0, while Windows Bayesian Inference Using Gibbs Sampling (WinBUGS V.1.4.3) is applied to generate Bayesian Network Meta-analysis (NMA) using Markov chain Monte Carlo algorithm. Forty RCTs are included, with 4405 participants. The effectiveness of six acupuncture techniques, three types of prophylactic drugs, and psychotherapy are compared and ranked. Acupuncture outperformed prophylactic drugs in terms of diminishing visual analog scale (VAS) score, migraine attack frequency, and days during the treatment and at the 12-week follow-up. At the 12-week follow-up, the effectiveness of various interventions is ranked as follows: manual acupuncture (MA) > electroacupuncture (EA) > calcium antagonists (CA) in reducing VAS score; MA > EA > CA in reducing migraine attack frequency; MA > EA > ß-receptor blocker and CA in reducing headache attack days. Acupuncture is a promising treatment for migraine prevention. The best option of acupuncture for improving various migraine outcomes has changed over time. However, the quality of included trials and NMA inconsistency limited the credibility of the conclusion.

[Developing process and term analysis of WFAS standard: General Requirements for the Risk Control in the Safe Use of Acupuncture].

In order to promote the application of WFAS standard, General Requirements for the Risk Control in the Safe Use of Acupuncture and the safe practice of acupuncture technology worldwide, the paper introduces the developing process and main contents of this standard, explains the developing purpose, scope, ideas, methods and basis, and analyzes the definition of the relevant terms. Through strictly complied with the development procedure of standard, the terms related to acupuncture risk in this standard are defined. The connotations of 5 special terms are clarified, i.e. "acupuncture risks" "adverse events of acupuncture" "adverse reactions of acupuncture" "acupuncture accidents" and "acupuncture negligence". The range, rank, control flow and source of risk, as well as the control measures are determined. The standard extracts the underlying common problems and basic requirement of the safe practice of acupuncture so as to lay a framework for the development of the relevant technical standards of acupuncture.

[Study on key outcome indexes in treatment of migraine with acupuncture and moxibustion].

OBJECTIVE: To identify the key outcome indexes in treatment of migraine with acupuncture and moxibustion. METHODS: Using literature research, questionnaire survey and consensus conference, the key outcome indexes in treatment of migraine with acupuncture and moxibustion were screened and prioritized. RESULTS: The critical outcome indexes for the treatment in attack stage of migraine included 6 effectiveness outcome indexes (headache intensity, headache duration, headache relieve time, effectiveness and level of headache relief within 2 h, headache-related quality of life, level of headache relief within 24 h) and 1 safety outcome index (incidence of serious adverse reactions). The critical outcome indexes for prophylactic treatment included 6 effectiveness outcome indexes (headache day, headache frequency, headache intensity, effective rate, headache-related quality of life, health-related quality of life) and 1 safety outcome index (incidence of serious adverse reactions). CONCLUSION: In terms of the attack stage treatment and prophylactic treatment with acupuncture and moxibustion, the outcome indexes are different, among which, those can directly reflect the conditions of migraine should be optioned in priority. To assess the effectiveness of attack stage, the headache intensity is preferred, using the visual analogue scale (VAS) score, and the preferred time is 2 hours after treatment. Regarding the effectiveness of prophylactic treatment, the headache day, headache frequency and headache intensity should be firstly considered in the assessment, in which, the preferred time for assessment is 12 weeks into treatment, while, the best time for follow-up should be 12 weeks after treatment completion. When the quality of life is considered, the migraine-specific quality of life questionnaire (MSQ) is the top option. For either the attack stage treatment or the prophylactic treatment, the high attention should be laid on the outcome indexes for safety and medical economics evaluation.

[WU Zhong-chao's clinical experience of "dredging stagnation and collaterals" acupuncture for migraine].

Professor WU Zhong-chao's clinical experience of "dredging stagnation and collaterals" acupuncture for migraine is summarized. Professor WU proposes that occiput-nape dysfunction, meridians-tendons dysfunction and stagnation of collaterals due to obstruction of excess-evil could lead to migraine. As such, migraine is treated by comprehensive treatment of adjusting occiput-nape functional zone, relaxing meridians-tendons and blood-letting combined with fire acupuncture.

[Problems in randomized controlled trial on acupuncture and moxibustion for migraine in the development of international standard of Guideline for Clinical Practice of Acupuncture and Moxibustion: Migraine].

Regarding the development of international standard of Guideline for Clinical Practice of Acupuncture and Moxibustion: Migraine, the existing problems of the design and methodology of randomized controlled trial (RCT) on acupuncture and moxibustion for migraine were summarized in views of participant, intervention, control, outcome and study design. Four directions need to be further explored, (1) research of adolescent migraine, special subtype of migraine and migraine in a special population; (2) research of the immediate analgesic effect of acupuncture and moxibuation at the attack stage of migraine and the therapeutic effect of migraine at each stage; (3) research on safety and health economics; (4) clinical trial registration of acupuncture and moxibustion. In study, the target population should be further determined and specialized, the diagnosis criteria of western medicine and traditional Chinese medicine be generalized and concentrated, the staging and type division of disease be accurate, the intervention procedure be integrated, the control design be rationalized, the outcomes be validated, and the description of randomization and blinding be clarified.

Investigation and Analysis of the Key Objectives of WFAS "Technical Specifications of Acupuncture and Moxibustion: General Rules for the Drafting".

OBJECTIVE: To determine the key objectives of WFAS "Technical Specifications of Acupuncture and Moxibustion: General Rules for the Drafting" (hereinafter referred to as General Rules). METHODS: From the medical institutions, colleges, and scientific research organizations at major levels in China and overseas, leading researchers and experts in the field of acupuncture-moxibustion standardization, as well as some experienced foreign specialists in acupuncture-moxibustion, were selected as the respondents. The questionnaire was prepared by using the website of Questionnaire Star, and 60 links of the questionnaire were sent out through e-mail. Excel was used to set up the database and conduct statistical analysis. RESULTS: Fifty-one valid questionnaires were collected with effective recovery rate of 85%, involving 9 countries (China, South Korea, Italy, Spain, Sweden, Norway, Netherlands, United States, and Canada) from 3 continents. Most experts agreed with us on the target people, structural elements, and text structure proposed in General Rules and held that the General Rules should emphasize the safety and international applicability and should stipulate in details the common problems (contraindications, indications, taboo crowd, target people, therapeutic effects) of various techniques and the specific contents of technical operation (manipulating techniques, selection of patient's body position and treated areas, disinfection and environmental requirements, selection of acupuncture-moxibustion instruments, cautions, needle retention time, treatment frequency, precise location of the acupoints, treatment course) in order to enhance the practicality and operability. CONCLUSION: The key objectives of General Rules mainly include target people, structural elements, text structure, safety requirements, common technical problems of acupuncture-moxibustion, and specific details of technical manipulations.

[Analysis of the results of international demand survey on Guideline for Clinical Practice of Acupuncture-Moxibustion: Migraine].

The survey is conducted prior to the development of international standard, Guideline for Clinical Practice of Acupuncture-Moxibustion: Migraine (Guideline) to determine the international demand. The survey includes 5 aspects, i.e. the application status of acupuncture and moxibustion abroad and the demand for the development of international standards, the priority of diseases developed by international standards, the necessity of the transformation of international standards from domestic standards, the key clinical problems to be solved by international standards, and the correlation between professional level and demand intention. The survey results show that the international demand of the Guideline is definite. Regarding the application range of acupuncture-moxibustion and the key clinical questions, the special consideration should be taken to the differences in the demands of the practitioners from different countries during the development of standard.

[Effect of acupuncture on the cognitive function of migraine patients with depression/anxiety disorder].

OBJECTIVE: To observe the effect of five-element acupuncture on the cognitive function repair of migraine patients with depression/anxiety disorder. METHODS: The migraine patients with depression/anxiety disorder (19 cases, 5 cases dropped off) were taken as the observation group, and received five-element acupuncture twice a week for 8 weeks. Healthy subjects (19 cases) were selected by demographic data matching as the control group. The cognitive function was evaluated with the event related potential (ERP) technique, and the latency and amplitude of visual evoked potential P300 were adopted as the observation indexes. The headache days (every 4 weeks), headache intensity [visual analogue scale(VAS) score], and headache impact test-6 (HIT-6) score, Hamilton depression scale (HAMD) score and Hamilton anxiety scale (HAMA) score were used as the observation indexes for curative effect. RESULTS: Before the treatment, latency of target stimulus at Fz [ (417.5±34.3) ms] in the observation group was extended compared with the healthy subjects of the control group [(388.6±42.1) ms, P<0.05]. In the observation group, the latency of each point target stimulus [Fz: (376.1±36.2) ms, F3: (374.8±37.6) ms, F4: (372.0±37.6) ms] after treatment were shorter than those [Fz: (417.5±34.3) ms, F3: (417.4±33.8) ms, F4: (416.0±36.6) ms] before treatment (P<0.05). Before and after treatment, there was no significant difference in the amplitude of each point between the observation group and the control group (P>0.05). In the observation group, the headache days was shorter than that before treatment (P<0.01), and the VAS score, HIT-6 score, HAMD score and HAMA score were all lower than before treatment (P<0.01). CONCLUSION: There are some cognitive impairments in migraine patients with depression/anxiety disorder. Five-element acupuncture not only relieves headache, anxiety and depression effectively, but also improves the activation level of the frontal lobe. It significantly repairs the impaired cognitive function.

[Analysis on development necessity and key points for Technical Specification of Acupuncture- Moxibustion: General Rules of Drafting of international industry organization standard].

This paper analyzes the development necessity of a series of international technical specification of acupuncture-moxibustion from three aspects, the development status of global Technical Specification of Acupuncture-Moxibustion, providing technical support for acupuncture-moxibustion legislation and assisting standardized acupuncture-moxibustion research. The necessity of giving priority to the development of WFAS's Technical Specification of Acupuncture-Moxibustion: General Rules of Drafting (General Rules for short) in the series of standards is discussed from filling the field gap and following the international practice. The key points should be paid attention to in the development process of General Rules are summarized，such as improving practicality based on international perspective, enhancing authority by following international rules, improving international applicability by forming a professional team and ensuring high quality and objective neutrality of the General Rules.

[Analysis on international demand investigation for technical specification of acupuncture- moxibustionthe and its general rules of drafting].

The electronic questionnaire was adopted to survey the international demand on Technical Specification of Acupuncture-Moxibustion: General Rules of Drafting (General Rules for short) to explore the potential problems during the application and provide the evidence for the development of international standard of General Rules. A total of 102 valid questionnaires were collected from 18 countries and regions. The priority of the demand for international standard on the technical specification of acupuncture-moxibustion is filiform needle, moxibustion, electroacupuncture, cupping, auricular acupuncture, scalp acupuncture and scraping. One hundred experts (98.04%) at home and abroad believe the necessity of the international standard development of General Rules. The awareness rate of the existing national standard of General Rules is 71.57% and the foreign experts think that its expression may be "unclear" and the domestic experts think it may be "lack of practicability". The domestic experts hope to highlight the commonness in the scope of the international standard of General Rules and the foreign experts hope to retain more individuality. Regarding the specific questions during the technique manipulations of acupuncture-moxibustion, there are the big differences in "relevant terminology" "preoperative preparation" and "adverse reaction and contraindications" at home and abroad. In order to improve the international compatibility and applicability, it is necessary to give full consideration to the needs of different countries in the development of international standard of General Rules and balance as far as possible between refining "common problems" and satisfying "individual needs".

[Professor WU Zhong-chao's clinical experiences of "syndrome differentiation and Chinese herbal plaster application" based on meridian and zangfu theories].

Focusing on the limits of the plaster application of Chinese herbal medicine in clinical practice, i.e. limit in the region exerted, inadequate meridian effect, more attention to the exterior rather than the interior and limit in the application of zangfu differentiation, professor WU Zhong-chao proposes his clinical experiences in the plaster application of Chinese herbal medicine based on meridian and zangfu differentiation, including: The Chinese herbal plaster application alone meridian course guided by meridian differentiation. Multidimensional plaster application on the base of the meridian differentiation of muscle region. Split-field plaster application by taking collateral differentiation as principle. Selective plaster application in association with disease differentiation. Specific plaster application rooted on zangfu differentiation.

[Transformation of the domestic standard (Guideline for Clinical Practice of Acupuncture-Moxibustion: Migraine) to international standard: in the perspective of the differences in clinical questions].

Through analyzing the differences in the clinical questions of Guideline for Clinical Practice of Acupuncture- Moxibustion: Migraine (Guideline) between the domestic standard and international standard (under development), the specific issues are determined in the transformation from domestic standard to international one. Taking acupuncture practitioners as investigation object, by means of the survey, the basic information and clinical questions were investigated. The survey results show that the following aspects should be supplemented in terms of the international requirements during the development of this international Guideline: suitable patient population, applicable types of disease, the optimal intervention time of acupuncture for migraine, common methods in treatment as well as the other involved health problems. Moreover, it needs to update the key clinical questions, recommended regimens for the newly supplemented types of disease, as well as the more specified assessment on therapeutic effect. The ultimate solution of these questions relies on the quality of clinical evidence.

[Moxa-stick moxibustion activates mast cells of small intestine tissue in rats].

OBJECTIVE: To explore the effect of moxa-stick moxibustion and joss-stick moxibustion at "Guanyuan" (CV4) on the activity of mast cells in the small intestine tissue in rats. METHODS: Twelve male SD rats were randomly divided into control, joss-stick moxibustion and moxa-stick moxibustion groups (n=4 rats in each group). Joss-stick or moxa-stick moxibustion was applied to CV4 for 10 min. After moxibustion, the skin temperature of the CV4 region was measured immediately with a thermometer. The mast cells and nerve fibers in the small intestine tissue were displayed by immunofluorescence histochemistry. RESULTS: Compared with the control group, the skin temperature of the CV4 region in both the joss-stick and the moxa-stick groups were significantly increased (P<0.05), while the skin temperature of the moxa-stick group was significantly higher than that in the joss-stick group (P<0.05). There were a large number of tryptase-positive mast cells in the small intestine of rats, some of which were co-expressed with lysosomal-associated membrane protein 1, displaying an activated state. The average numbers of mast cells in the control, joss-stick and moxa-stick groups were 9.2±3.6, 10.8±5.3 and 17.1±6.3, respectively, being significantly higher in the moxa-stick group than in the control and joss-stick groups (P<0.05). In addition, calcitonin gene-related peptide(CGRP) and neuropeptide Y(NPY) positive nerve fibers were found around the mast cells in the small intestinal tissues. CONCLUSION: Moxa-stick moxibustion gives rise a higher temperature at CV4 to activate mast cells surrounded by CGRP and NPY positive nerve fibers in the small intestine tissue in rats, suggesting an involvement of the sensory and sympathetic nervous system in the activation of intestinal mast cells possibly by way of somatic sympathetic reflex.

No sex difference in overall P-glycoprotein activity as assessed by talinolol disposition in humans.

PURPOSE: The aim of this study was to investigate the sex-dependent difference in P-glycoprotein activity as measured by the probe drug talinolol. METHODS: A randomized, single-blind, parallel study was carried out in 20 healthy male and 20 healthy female volunteers. The pharmacokinetics of talinolol were measured after single oral dosing of 50-mg tablet and the pharmacokinetic parameters for male and female subjects were compared after excluding the potential influence of P-gp genetic polymorphisms. RESULTS: Talinolol AUC(0-48h) in the female subjects was 23.5% (p = 0.003) higher than that of male subjects. There was no significant sex difference in weight-corrected oral clearance, AUC, or other PK parameters. CONCLUSION: The AUC and other PK data of talinolol, corrected for body weight, did not differ between genders after oral administration. The observed sex difference in talinolol systemic exposure is of little clinical relevance. The overall activity of P-gp shows no sex-related difference.

Similar Outcomes of Standard Radiotherapy and Hypofractionated Radiotherapy Following Breast-Conserving Surgery.

BACKGROUND: Adjuvant radiation therapy is commonly administered to breast cancer patients who received breast-conserving surgery. However, lengthy treatment times of standard radiotherapy pose certain challenges. Here, we performed a prospective controlled study comparing standard radiation to hypofractionated radiotherapy in terms of efficacy and outcome. MATERIAL AND METHODS: Eighty breast cancer patients (tumor stage pT1-2N0-1M0) who had undergone breast-conservation surgery were randomly divided into 2 groups (40 patients/group). The experimental group received 43.2 Gy to the whole breast in 18 fractions for 24 days with a concomitant boost (50.4 Gy) to the tumor bed. The control group received 45 Gy to the whole breast in 25 fractions for 44 days with a boost to the tumor bed of 59 Gy. Survival, locoregional recurrence, adverse effects, and aesthetic results were all considered for analysis. RESULTS: The following criteria were included as part of study follow-up: local control, survival, adverse skin reactions, cosmetic outcome, and hematological toxicity. At a median follow-up of 27 months (follow-up rate 100%), there were no statistical differences in any of the categories between the 2 groups. The 2-year survival rate of both groups was 100% without any locoregional recurrence. Although there was some skin toxicity, these instances were not severe and they cleared on their own within 6 weeks. The most common problems encountered by patients were breast fibrosis and altered pigmentation. CONCLUSIONS: A shortened whole-breast hypofractionated irradiation schedule with a concomitant boost is as effective as standard radiation and may be a reasonable alternative following breast conservation surgery.

[Comparison of the therapeutic effect on skeletal fluorosis and impact on urine fluoride value among fire needle therapy, electroacupuncture and calcium carbonate D3].

OBJECTIVE: To observe the impacts on skeletal fluorosis pain, joint motor dysfunction and urine fluoride excretion in the treatment with fire needle therapy, electroacupuncture and calcium carbonate D3. METHODS: The randomized controlled trial was adopted. Ninety-five patients were randomized into a fire needle group (31 cases), an electroacupuncture group (33 cases) and a calcium carbonate D3 group (31 cases). In the fire needle group and the electroacupuncture group, Ashi points, Dazhui (GV 14), Geshu (BL 17), Quchi (LI 11), Hegu (LI 4), Xuehai (SP 10) points were selected and stimulated with fire needle and electroacupuncture separately, three times a week. In the calcium carbonate D3 group, calcium carbonate D3 tablets was prescribed for oral administration, 600 mg each time, twice a day. The duration of treatment was 2 months in the electroacupuncture group and calcium carbonate D3 group and 1 month in the fire needle group. VAS score, the range of motion (ROM) and urine fluoride value were compared before and after treatment in the patients of the three groups. RESULTS: After treatment, VAS value and ROM were improved significantly in the patients of the three groups (all P < 0.05), the difference was not significant in comparison of the three groups (all P > 0.05). After treatment, the urine fluoride value was increased significantly in the fire needle group [(7.89 +/- 3.61) mg/L vs (9.81 +/- 4.17) mg/L, P < 0.01] and was increased in the electroacupuncture group [(7.53 +/- 3.46) mg/L vs (8.97 +/- 4.21) mg/L, P < 0.05]. The difference was not significant in comparison before and after treatment in the calcium carbonate D3 group (P > 0.05). CONCLUSION: The fire needle therapy, electroacupuncture and calcium carbonate D3 all have the clinical value in the prevention and treatment of skeletal fluorosis and the difference in the therapeutic effect has not been discovered among them yet at present. But it has been found that the fire needle therapy and electroacupuncture display the active significance in the promotion of urine fluoride excretion.

Late course accelerated hyperfractionation radiotherapy for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Late course accelerated hyperfractionation radiotherapy (LCAHR) is used as a standard treatment option for locally advanced esophageal squamous cell carcinoma (LAESCC) in China, but concerns remain regarding its efficacy and safety. The purpose of this paper was to evaluate the efficacy and safety of LCAHR. The comparisons examined were as follows: LCAHR versus conventional fractionation radiotherapy (CFR) and LCAHR plus chemotherapy (CT) versus LCAHR alone. METHODS: We searched the Cochrane Library, MEDLINE, EMBASE, CENTRAL, CBMdisc, and CNKI, as well as employing manual searches. The primary end points were survival and local control. The second end point was toxicities. RESULTS: Based on search criteria, we found 29 trials involving 3187 patients. Our results showed that LCAHR, compared with CFR, improved the survival and local control, and was, thus, more therapeutically beneficial. Further analysis revealed that LCAHR plus CT proved to be better for patients' survival and local control compared to LCAHR alone. Acute toxicities were increased rather than late toxicities. CONCLUSIONS: There was a significant survival and local control benefit of LCAHR over CFR, as well as LCAHR plus CT over LCAHR alone. Considering the strength of the evidence, the results of this study indicate that this regimen would be a new promising modality worth further investigation.

[Study on the impacts of different time of moxibustion on regulating lipid effects of hyperlipidemia].

OBJECTIVE: To observe the impacts of different time of moxibustion on its regulating lipid effects and safety of hyperlipidemia. METHODS: Seventy-six cases of hyperlipidemia patients were randomly divided into three groups: including moxibustion 10 min group (group A, 25 cases), moxibustion 20 min group (group B, 25 cases) and moxibustion 30 min group (group C, 26 cases). All of these three groups choose the same acupoints, Shenque (CV 8),Zusanli (ST 36), Fenglong (ST 40) and Sanyinjiao (SP 6) were selected. These three groups were treated with moxibustion for 10 min, 20 min and 30 min, respectively, three times a week, 12 times constituted one course, two courses were required for each group. All indices of blood lipid and fasting blood glucose were observed before and after treatment, and the preliminary evaluation was made on the safety of hepatic and renal function. RESULTS: There were significant decrease in total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and blood sugar after moxibustion treatment (all P<0.001), there was no significant difference of high density lipoprotein cholesterol (HDL-C) before and after treatment (P>0.05). The group C played more prominent role than group A in regulating the TC (P<0.01) and LDL-C (P<0.05), there was no significant difference between group C and group B (P>0.05). The blood urea nitrogen(BUN) was significantly reduced after moxibustion treatment (P<0.05), and there were no significant differences of other safety indices before and after treatment (all P>0.05). CONCLUSION: Moxibustion can effectively and safely reduce the blood lipid level of hyperlipidemia patients, the decreasing degree of lipid is different with different time of moxibustion after treatment, and the decreasing degree in moxibustion 30 min group is significantly better than that in moxibustion 10 min group.

[Drinking-water type fluorosis treated with acupuncture of reinforcing kidney and activating spleen: a randomized controlled trial].

OBJECTIVE: To observe the impacts of acupuncture of reinforcing kidney and activating spleen on the excretion of urinary fluoride and pain of the patients with drinking-water type fluorosis. METHODS: The randomized controlled and single-blind trial was adopted. Seventy-two cases were randomized into an observation group and a control group, 36 cases in each one. In the observation group, acupuncture was applied at Pishu (BL 20), Shenshu (BL 23), Guanyuan (CV 4), Zusanli (ST 36), etc. , three treatments a week. In the control group, the Calcium Carbonate D3 tablets were prescribed for oral administration, 600 mg each time, twice a day. The duration of treatment was 2 months. The changes of the content of urinary fluoride and pain score (by VAS) before and after treatment between two groups were compared. RESULTS: The urinary fluoride excretion was increased obviously after treatment in the observation group (P < 0.01), which was superior apparently to that in the control group [(11.06 +/- 4.54) mg/L vs. (8.30 +/- 4.14) mg/L, P < 0.05]. After treatment, VAS score was reduced significantly in either group (both P < 0.01). The result in the observation group was lower remarkably than that in the control group (1.93 +/- 1.30 vs. 3.47 +/- 2.29, P < 0.01). CONCLUSION: Acupuncture achieves the significant efficacy on the promotion of urinary fluoride excretion and pain relieving of the patients with drinking-water type fluorosis in light of reinforcing kidney and activating spleen, which is superior to the oral administration of the calcium carbonate D3 tablets.