Clinical Observation on 34 Cases of Chronic Atrophic Gastritis Treated with Shenlian Twelve Flavors

Jincheng WANG, Sufang ZHOU, Leiming MAO, Jiao XU, Chuang LIU*

1. Graduate School of Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; 2. The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China

Abstract [Objectives] The research aimed to observe the curative effect of Shenlian Twelve Flavors in treating CAG patients with spleen deficiency and blood stasis toxin. [Methods] 66 cases of CAG patients with spleen deficiency and blood stasis toxin were selected, 32 cases in the control group and 34 cases in the observation group were generated according to the random number table method. The control group was treated with Moluodan; the observation group was treated with Shenlian Twelve Flavors. After treatment, the effective rate, TCM symptom score, gastroscopic score, pathological score, serum gastrin 17 (G-17) level, and adverse reactions were compared between the two groups. [Results] The total effective rates of control group and observation group were 84.37% and 91.18%, respectively, and there was no statistical significance between the two groups (P>0.05). For the improvement of TCM symptom score, both groups were improved significantly compared with that before treatment, and observation group was better than control group (P<0.05). For the improvement of gastroscopic score, both groups were improved compared with that before treatment, and observation group was better than control group (P<0.05). For the improvement of pathological scores, both groups were improved compared with that before treatment, but there was no statistical significance between the two groups (P>0.05). [Conclusions] Shenlian Twelve Flavors has definite clinical efficacy in the treatment of CAG with spleen deficiency and blood stasis toxin. It could improve clinical symptoms, delay pathological progress, and regulate the level of G-17. There is no obvious adverse reaction, and it is worthy of clinical reference.

Key words Shenlian Twelve Flavors, Spleen deficiency and blood stasis toxin, Chronic atrophic gastritis

1 Introduction

Chronic atrophic gastritis (CAG) is a type of chronic gastritis. It is a chronic gastric disease characterized by atrophy or reduction of proper glands of gastric mucosal epithelium, or accompanied by intestinal metaplasia, and is also main precancerous disease[1]. The research and survey[2]show that with the change of dietary behavior and the popularization of endoscopy, the prevalence and diagnostic rate of CAG also increase year by year. Therefore, active and effective prevention and treatment of CAG is a key step in the intervention of precancerous lesions of gastric cancer. At present, western medicine treatment[3]is based on the principle of removing the cause of disease, alleviating symptoms and improving gastric mucositis reaction. Combined therapy of drugs of anti infection, protecting gastric mucosa, and acid inhibition is often used, but the overall effect is poor. Traditional Chinese medicine points out that the disease is located in the stomach, which is closely related to the liver and spleen. The cause of the disease is based on the weakness of the spleen and stomach, with the evil of dampness, heat, blood stasis and toxin. Using the characteristics of traditional Chinese medicine, it has obvious advantages in alleviating the clinical symptoms of CAG, improving the pathological changes of gastric mucosa, and intervening in the transformation of "inflammation-cancer"[4]. A number of clinical studies have confirmed that traditional Chinese medicine can indeed reduce inflammatory factors, and improve body immunity, thereby strengthening the protection and healing of gastric mucosa, and effectively intervening the progress of CAG[5]. Based on the theory of "spleen deficiency and blood stasis toxin" of Professor Zhou Sufang, famous traditional Chinese medicine in Guizhou Province and academic inheritor of Professor Wu Wenyao who is national famous and old expert of traditional Chinese medicine[6], Shenlian Twelve Flavors was used to intervene CAG and had obtained certain curative effect.

2 Data and methods

2.1 General informationCAG patients of spleen deficiency and blood stasis toxin type treated in the Department of Gastroenterology, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from March of 2021 to March of 2022 were selected. The random number table method was used to generate 34 cases in the observation group and 32 cases in the control group. Observation group: 16 females and 18 males; 41-76 years old, and average age of (56.09±9.624); 1-8 years of disease course, and average disease course of (4.06±1.808) years. Control group: 19 females and 13 males; 46-70 years old, and average age of (55.84±6.975); 1-8 years of disease course, and average disease course of (4.28±1.397) years. There was no difference in gender, age and course of disease between the two groups (P>0.05), and baseline data was comparable.

2.2 Diagnostic criteria(i) Diagnostic criteria of western medicine: corresponding with diagnostic criteria of CAG in theChineseConsensusonChronicGastritison2017[3]. Endoscopic examination shows that the mucosa is red alternating with white, and most is white. The mucosa becomes thinner, and the blood vessels are exposed, showing granular or nodular changes. Pathological biopsy shows atrophy or intestinal metaplasia of the inherent glands. (ii) Diagnostic criteria of traditional Chinese medicine: referring to theConsensusonDiagnosisandTreatmentofChronicAtrophicGastritiswithIntegratedTraditionalChineseandWesternMedicinein2017[7]and theConsensusonTCMDiagnosisandTreatmentofChronicAtrophicGastritisinLingnanArea[8], spleen deficiency and blood stasis toxin type is formulated: the main symptom is stomach pain or stomach distention; the secondary symptoms are acid reflux, heartburn, hiccup, stupidity, and fatigue; the tongue is dim or has petechiae and ecchymosis; pulse is thin or stringy or astringent.

2.3 Inclusion criteriaThose who meet the diagnosis of traditional Chinese and Western medicine at the same time; the patient who has no history of major diseases and psychosis, and the age of illness is between 18 and 80 years old; patients who signed informed consent.

2.4 Exclusion criteriaThose who do not meet the diagnosis of traditional Chinese and Western Medicine; patients who are younger than 18 years old or older than 80 years old; pregnant or lactating patients; patients who are allergic to drug ingredients; people with bad living habits;Helicobacterpyloriinfection (HP positive).

2.5 Therapeutic methodControl group: treated with Moluodan. Moluodan (Handan Pharmaceutical Co., Ltd.), approval No.:GUOYAOZHUNZI Z20090013, format: 18 bags/16 pills. Medication method: oral, 16 pills/bags at a time, three times a day. Observation group: adding or subtracting Shenlian Twelve Flavors according to syndrome differentiation (Pseudostellariae Radix 15 g, Macrocephalae Rhizoma 15 g, Poria 15 g, Coicis Semen 20 g, Herba Hedyotidis 15 g, Scutellariae Barbatae Herba 15 g, Curcumae Rhizoma 10 g, Bulb of Thunberg Fritillary 10 g, Arcae Concha 15 g, Hordei Fructus Germinatus 18 g, Galli Gigerii Endothelium Corneum 10 g, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle 6 g)[9-11]. For the patients with hiccup and belching, it selected to add Lignum Aquilariae Resinatum, Albergiae Odoriferae Lignum, and Haematitum. For the patients with acid reflux and heartburn, it selected to add Oyster Shell, Euodiae Fructus, and Coptidis Rhizoma. For the patients with epigastric cold pain, it selected to add Alpiniae Officmarum Rhizoma, Zingiberis Rhizoma, and Cinnamomi Cortex. For the patients with fullness and abdominal distension, it selected to add Magnoliae Officmalis Cortex, Curcumae Radix, and Rosae Rugosae Flos. For the patients with mucosal ulcer and bleeding by endoscope, it selected to add Bletillae Rhizoma, Notoginseng Radix Et Rhizoma, and Cattail Pollen. Medication method: decocted in water for oral dose, one dose a day, once in the morning, once in the afternoon and once after dinner. The above traditional Chinese medicines were provided by the Outpatient Chinese Pharmacy of Guizhou University of Traditional Chinese Medicine. Both groups were treated continuously for 3 months. During the treatment period, the patients were given disease health awareness education and cooperated with the control of good eating and living habits.

2.6 Observation indexes(i) Efficacy comparison: formulated by referring to theGuidingPrinciplesforClinicalResearchofNewChineseMedicines[12]and theExpertConsensusonQuantitativeCriteriaforSymptomsofSpleenandStomachDiseases[13]. Clinical recovery: the main clinical symptoms, signs, endoscopic manifestations and pathological manifestations disappeared completely or basically, and efficacy index was more than 95%. Clinically remarkable effect: the main clinical symptoms, signs, endoscopic manifestations and pathological manifestations were significantly improved, and 70%≤efficacy index<95%. Clinically effective: the main clinical symptoms, signs, endoscopic manifestations and pathological manifestations were improved, and 30%≤efficacy index<70%. Invalid: the main clinical symptoms, signs, endoscopic manifestations and pathological manifestations were not significantly improved, or even aggravated, and efficacy index≤30%. It was calculated by nimodipine method. (ii) TCM symptom score: formulated by referring to theExpertConsensusonQuantitativeCriteriaforSymptomsofSpleenandStomachDiseases[13]. The 13 symptoms of stomach pain, gastric distension, belching, acid regurgitation, heartburn, early satiety, nausea, vomiting, putrid belching and acid swallowing, stomach noise, poor appetite, boredom and hiccup were scored as 0, 1, 2 and 3, respectively. (iii) Gastroscope score: formulated by referring to the literature. Main lesions: vascular exposure, rough mucosa, granular nodule changes; classification: none, light, medium and serious, and they were scored as 0, 2, 4, 6. Secondary lesion: mucosal erythema and mucosal erosion; classification: none, yes, and they were scored as 0 and 1, respectively. Bile reflux, classification: none, light, medium and serious, and they were scored as 0, 1, 2 and 3. (iv) Pathological score: formulated by referring to the literature. Atrophy, intestinal metaplasia and dysplasia were classified as none, light, medium and serious, with scores of 0, 2, 4 and 6, respectively. The grades of active inflammation were none, light, medium and serious, with scores of 0, 2, 4 and 6, respectively. (v) Level of serum gastrin 17 (G-17): checked in laboratory, and 3 mL fasting venous blood samples of patients before and after treatment. ELISA method was used to detect gastrin17 (G-17), and it needed to strictly follow the instructions of the kit. (vi) Adverse reactions: adverse reactions of patients during treatment.

3 Results and analysis

3.1 Comparison of clinical efficacy between the two groups

Effective rates in control and observation groups were 84.37% and 91.18%. There was no statistical significance between the two groups (P>0.05), but effective rate of observation group was higher than control group (Table 1).

Table 1 Comparison of clinical efficacy between two groups after treatment cases (%)

3.2 TCM symptom scoreAfter treatment, the improvement of symptom score in the two groups was better than those before treatment, and the improvement of total symptom score in the observation group was better than that of the control group, with statistical significance (P<0.05, Table 2).

3.3 Gastroscope scoreAfter treatment, the improvement of gastroscope score in the two groups was better than that before treatment. The improvement of gastroscope in the observation group was better than that in the control group, with statistical significance (P<0.05, Table 2).

3.4 Pathological scoreThe improvement of pathological score in the two groups after treatment was better than that before treatment. There was no significant difference between the observation group and the control group (P>0.05, Table 2).

Table 2 Comparison of improvement of TCM symptom, gastroscope and pathological scores between the two groups before and after treatment

3.5 Level of serum gastrin 17 (G-17)The improvement of G-17 level in two groups after treatment was better than that before treatment. The G-17 level in observation group had no statistical significance when compared with control group (P>0.05, Table 3).

Table 3 Change of serum gastrin 17 (G-17) level in two groups before and after treatment

3.6 Adverse reactionsDuring the treatment period, both groups of patients had no obvious discomfort symptoms.

4 Discussion

CAG is an important precancerous disease of gastric cancer. Because of its high correlation with the development of gastric cancer, the phenomenon of "becoming pale even at the mention of talking about CAG" is becoming more and more sensitive, and the outpatient treatment rate is also increasing year by year. According to the different clinical symptoms, it can be roughly classified as "stuffiness of stomach" and "epigastric pain" in traditional Chinese medicine. Its pathogenesis is mainly related to various factors such as disordered diet and poor mood. The pathogenesis is mainly weakness of the spleen and stomach, with the evil of dampness, heat, blood stasis and toxin. The main principle of treatment is strengthening the spleen and nourishing the stomach, taking into account the elimination of other evils.

Zhou Sufang, chief physician, combined with his years of clinical experience and regional characteristics, believes that this disease, whether congenital or acquired, is caused by spleen and stomach damage and weakness of the spleen and stomach. If the spleen and stomach are weak, it cannot be transported, and there are pathological states such as dampness evil, qi stagnation, phlegm obstruction, blood stasis,etc.For a long time, disease evil enters the collaterals. In Guizhou, dampness evil prevails. People like to eat spicy and greasy food, which is the key to the damage of the spleen and stomach. Dampness evil, phlegm turbid and blood stasis enter the collaterals, become toxic after a long time, and damage gastric mucosa, and it eventually develops into chronic atrophic gastritis. Based on the further understanding of the theory of "spleen deficiency and blood stasis toxin", the Shenlian Twelve Flavors was created. This prescription has the functions of strengthening the spleen, supplementing qi, removing blood stasis and toxin. In the prescription, Pseudostellariae Radix and Macrocephalae Rhizoma increase the qi of spleen and stomach, together as principle drug. The combination of Poria and Coicis Semen is dedicated to infiltrating dampness and strengthening the spleen, assisting principle drug to promote the transportation of the spleen and stomach, and supporting the healthy qi to consolidate the foundation. Herba Hedyotidis and Scutellariae Barbatae Herba are used for reducing inflammation, detoxification and anticancer. Curcumae Rhizoma is used for promoting qi and blood circulation, removing blood stasis and detoxification. Bulb of Thunberg Fritillary and Arcae Concha are good at inhibiting acid and relieving pain, all of which are minister drug. Hordei Fructus Germinatus and Galli Gigerii Endothelium Corneum are used for invigorating the spleen and stomach, regulating qi and eliminating conduction, which not only strengthens the efficacy of principle and minister drugs, but also prevents nourishing and greasy, and can also direct the qi breaking descent of Curcumae Rhizoma. They are assistant drugs. Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle is sweet in nature, and could tonify and harmonize the various drugs, which is taken as envoy drug. Modern pharmacological research shows that Pseudostellariae Radix[14]has the effects of immune regulation and antioxidant stress. Macrocephalae Rhizoma[15]can repair gastrointestinal mucosal damage and inhibit the growth and proliferation of gastric cancer cells through anti-inflammatory active ingredients. Herba Hedyotidis-Scutellariae Barbatae Herba[16]can antagonize the inflammation of gastric mucosa, resist oxidation, regulate tumor cells, and have anti-inflammatory and anti-cancer effects. Curcumae Rhizoma[17]can inhibit the proliferation of gastric cancer cells and interfere with gastritis-cancer transformation.

The research results showed that total effective rates in control group and observation group were 84.37% and 91.18%, and there was no significant difference between the two groups (P>0.05). It indicated that both groups had practical clinical effects on the disease, but whole efficacy of Shenlian Twelve Flavors was better than Moluodan. For the improvement of TCM symptom score, two groups were both improved obviously than that before treatment, and observation group was better than control (P<0.05). It indicated that Shenlian Twelve Flavors had better improvement effect on clinical discomfort symptoms. For the improvement of gastroscopy score, both two groups were improvement than that before treatment, and observation group was better than control (P<0.05). It indicated that Shenling Twelve Flavors was superior to Moluodan in improving and repairing gastric mucosa. For the improvement of pathological score, both groups were better than that before treatment. However, there was no statistical significance between the two groups (P>0.05). It showed that Shenling Twelve Flavors was not inferior to Moluodan in improving the pathological progress of gastric mucosa. The regulation effect of G-17 by Shenling Twelve Flavors was similar to the research report of Yang Qianetal[18]. It was suggested that the prescription may participate in regulating G-17 level to intervene CAG. There was no obvious adverse reaction in both groups. In conclusion, the research results showed that Shenling Twelve Flavors had definite clinical effects for improving clinical symptoms of CAG, endoscopic appearance of gastric mucosa, pathological tissue expression of gastric mucosa, and G-17, with better safety. It is worthy of clinical promotion, and provides a reference for further actively exploring the prevention and treatment of CAG with traditional Chinese medicine, intervening in precancerous disease, and giving full play to the characteristic treatment advantages of traditional Chinese medicine.