Efficacy and safety of combining Chinese medicine with Western medicine for gallstone treatment

Abstract

Background:

Background gallstones are a common and multiple disease, with a high global prevalence, complications such as cholecystitis, pancreatitis, and even increased risk of cancer. Oral Chinese medicine, as the main treatment method of traditional Chinese medicine, is widely used in the treatment of gallstones. This study aimed to evaluate the efficacy and safety of Chinese medicine combined with Western medicine for the treatment of gallstones.

Methods:

We searched PubMed, Web of Science, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, WanFang, Chinese Scientific Journal Database (VIP), and Chinese BioMedical Literature Database. The search time was set to be up to July 2, 2024. Data analysis using Revman 5.3 software. The protocol is registered in the PROSPERO database (CRD42024567327).

Results:

Ultimately, 912 patients from 8 randomized controlled trials were included. The meta-analysis results of traditional Chinese medicine combined with Western medicine versus Western medicine were as follows: imaging examination (standardized mean difference, SMD = −1.51, 95% confidence interval [CI] (−2.36, −0.65), P < .001), total cholesterol level (SMD = −2.14, 95% CI (−3.61, −0.67), P = .004), total bile acid level (SMD = -0.97, 95% CI (−3.36, −1.42), P = .043), traditional Chinese medicine symptom scores (SMD = −1.88, 95% CI (−3.16, −0.60), P = .004), occurrence of adverse reaction (odds ratio = 0.51, 95% CI (0.21, 1.24), P = .14).

Conclusion:

The curative effect of Chinese medicine combined with Western medicine in the treatment of gallstones is better than that of Western medicine and is safety. Due to the limited quantity and quality of the included literature, more literature on double-blind randomized controlled trials with large samples is needed in the later stage to verify this conclusion.

1. Introduction

Gallstones are a common and frequent disease affecting 6% of the global population, and their incidence is increasing annually.^[1] Gallstones can cause cholecystitis, pancreatitis, and other diseases, and have a high correlation with gallbladder cancer.^[2–4] Gallstones can stimulate the gallbladder mucosa tissue, cause inflammation and damage, and put the human body in a long-term inflammatory state, thereby increasing the risk of gallbladder cancer.^[5] At present, cholecystectomy is the first choice for the treatment of gallstones.^[6] The maximum cumulative recurrence rate after 23 years of choledochoscopic cholecystolithotomy is 7.94%,^[7] while the recurrence rate after 4 years of stone drug treatment is more than 40%.^[8] Although the recurrence rate of drug treatment is higher than that of surgical treatment, the cost of surgical treatment is expensive,^[9] for example, cholecystectomy in the United States costs nearly 6.5 billion US dollars per year,^[10] and it is difficult for disadvantaged patients in society to receive surgical treatment immediately.^[11,12] In China, Consensus cholelith disease combine traditional Chinese and Western medicine diagnosis and treatment (2017)^[13] proposed that patients with small stones (diameter < 10 mm) may be treated with traditional Chinese medicine (TCM) combined with Western drugs with stone removing effect such as chenodeoxycholic acid, but no effective clinical data demonstration and unified diagnosis and treatment plan were provided. This article aims to evaluate the advantages and disadvantages of integrated traditional Chinese and Western medicine in the treatment of symptomatic gallstones, to provide a better non-surgical treatment for older patients or those unwilling to operate, and to reduce the economic burden of patients and medical care.

2. Methods and materials

2.1. Protocol registration

This systematic review and meta-analysis were based on the guidelines of the Preferred Reporting Project for Systematic Reviews and Meta-Analyses (PRISMA). The meta-analysis was registered on the PROSPERO platform (CRD42024567327). Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails,CRD42024567327.

2.2. Search strategy

We searched PubMed, Web of Science, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, WanFang, Chinese Scientific Journal Database, and Chinese BioMedical Literature Database from their establishment to July 2, 2024. Keywords: TCM, Gallstone(s), Gall Stone(s), randomized controlled trial (RCT). It uses a combination of subject terms and is free to search for and adjust according to the characteristics of each database. There are no restrictions on language, publication time, or research location. The search terms used are shown in File S1, Supplemental Digital Content, https://links.lww.com/MD/P282.

2.3. Inclusion and exclusion criteria

2.3.1. Inclusion criteria

(1) RCTs comparing Chinese herbal remedies for gallstones; (2) the study population comprised patients aged 18 years and over with symptomatic gallbladder stones, as defined by international diagnostic criteria. Patient inclusion was not limited by race, nationality, language, or disease course. (3) The treatment group was treated with Chinese medicine combined with western medicine, and the efficacy of Chinese medicine was unlimited. The control group was treated with Western medicine. (4) The main outcome indicators were: (i) imaging improvement; (ii) blood analysis: total cholesterol (TC) and total bile acids (TBA); and (iii) TCM symptom scores. (5) The secondary outcome was the occurrence of adverse reactions.

2.3.2. Exclusion criteria

(1) The literature records data that is either missing or unknown, and there is no evidence of a primary outcome or secondary outcome indicators. (2) The study was conducted on patients who had undergone surgery, acupuncture, or a combination of acupuncture and herbal tonics.

2.4. Data extraction

Two researchers (T.P.J. and W.J.Y.) completed preliminary screening by the title and abstract of the retrieved studies respectively, and screened again by reading the full text to select the studies that met the inclusion and exclusion criteria. If there is disagreement, a consensus should be reached through in-depth discussion, and if no consensus can be reached, the third researcher (J.T.D.) will further evaluate and extract the information for cross-checking. Data extraction mainly included the following contents: study name, publication year, first author, country, sample size, intervention measures, treatment duration, outcome indicators, etc. If the outcome data from the included RCT is incomplete, the reason for the data loss should be found in the original article, or excluded if not found.

2.5. Literature quality assessment

Two researchers (T.P.J. and W.S.O.Y.) developed the Cochrane Collaboration Assessment Tool and the Cochrane Collaboration’s Risk of Bias Assessment Criteria. The methodological quality of each included paper was independently assessed. It includes the following characteristics: random sequence generation, assignment concealment, blinding, incomplete outcome data, selective reporting, and other biases.

2.6. Statistical analysis

RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) was used for statistical analysis. The standardized mean difference (SMD) was used for continuous variables, and the odds ratio (OR) was used for dichotomous variables. The effect magnitude when the treatment group and the control group were juxtaposed was summarized with 95% confidence interval (CI). Intrinsic heterogeneity was assessed using the χ² test, and I² values were quantified. A value of I² ≤ 50% and P ≥ .1 indicated that the studies were homogeneous, suggesting that there was no statistically significant difference, so a fixed effects model could be used. In contrast, I² values > 50% and P ≤ .1 indicate significant heterogeneity, suggesting statistically significant differences, and a random effects model should be used to analyze the data. To test the robustness of the results, a sensitivity analysis was performed by excluding the included studies one by one to explore the potential sources of heterogeneity. If the observation index included more than 10 studies, the funnel plot was used to test the possibility of bias risk. If there were fewer than 10 items, there was no need to test the analysis for bias.

3. Results

3.1. Search results

A preliminary search of 3247 potentially relevant articles on TCM treatment of gallstones was conducted from the database, and 780 duplicate records were deleted. Then 2443 articles were excluded by reviewing titles and abstracts. After reading the full text and checking against the inclusion and exclusion criteria, 16 articles were excluded. As a result, a total of 8^[14–21] published articles were included in the meta-analysis (Fig. 1).

Figure 1.

Literature screening process and results. A preliminary search of 3247 potentially relevant articles on traditional Chinese medicine treatment of gallstones was conducted from the database, and 780 duplicate records were deleted. Then 2443 articles were excluded by reviewing titles and abstracts. After reading the full text and checking against the inclusion and exclusion criteria, 16 articles were excluded. As a result, a total of 8^[14–21] published articles were included in the meta-analysis. RCT= randomized controlled trial. The graphic framework is from Page et al,^[22] licensed under CC BY 4.0.

3.2. Research characteristics

The 8 studies that met the inclusion and exclusion criteria had a total of 912 adult participants with gallstones. There were 458 cases in the control group and 454 cases in the treatment group. All studies had clear inclusion and exclusion criteria, and there were no significant differences in baseline information between control and treatment groups. All the intervention measures in the treatment group were Chinese medicine combined with Western medicine (Table 1). The TCM commonly used in the treatment group were rhubarb, scutellaria scutellaria, pectinia, Yujin, and so on (Table 2). The details of Chinese medicine are described in Table S1, Supplemental Digital Content, https://links.lww.com/MD/P283. The control group in all studies was treated with Western medicine.

Table 1.

Basic characteristics of the 8 studies included in the meta-analysis.

Inclusion studies	Country	Number(T/C)	Patient age (years)	Treatment group	Control group	Duration	Outcome
Wang (2015)[14]	China	46/43	T:43.25 ± 10.48 C:45.74 ± 9.59	Oral TCM decoction (300 mL, bid) + C	Cefoperazone and sulbactam were given intravenously (2 g bid)(If the pain is severe, appropriate analgesic drugs should be given))	4 weeks	(2), (3), (5), (6), Clinical symptom score
Zhao (2017)[15]	China	63/63	T:46.5 ± 5.6 C:45.7 ± 5.2	Oral Danqing capsule(3–5 capsules, tid) + C	Oral UDCA (250 mg, qd)	2 months	(1) (Stone diameter), (4), (5), (6), Pain level (VAS)
Liang (2019)[16]	China	74/73	T:41.34 ± 5.63 C:42.82 ± 6.82	Oral Chaijin Huayu formula (bid) + C	Oral UDCA (500 mg, qd)	12 weeks	(1) (Gallbladder emptying rate), (4), (5), (6), SF-36 rating, CCK-A and VIP
Liu (2019)[17]	China	100/100	T:55.5 ± 3.6 C:55.0 ± 3.5	Oral Xiaoshilidan capsule (3.6 g, tid) + C	Analgesic, anti-inflammatory, antispasmodic and other conventional treatment + Oral UDCA (qd)	2 months	(1) (Stone diameter), (5), Pain rating, Incidence of postoperative complications
Zhou (2020)[18]	China	43/43	T:48.77 ± 7.66 C:48.74 ± 7.65	Oral Xiaoshilidan capsule (1.2 g, tid) + C	Analgesic, anti-inflammatory and other basic treatment + Oral UDCA (qd)	8 weeks	(1)(Stone diameter), (4), (6), Pain rating, Inflammatory factor
Li (2021) [19]	China	45/45	T:41.5 ± 23.5 C:41.5 ± 23.5	Oral Yin Chen Hao Tang added flavor (200 mL, bid) + C	Oral UDCA (50 mg, bid)	4 weeks	(4), (6), white blood cells, bilirubin, Curative effect
Lou (2021)[20]	China	52/52	T:41.4 ± 4.1 C:41.5 ± 4.3	Oral Big bupleurum decoction plus minus (400 mL, bid) + C	Intravenous cefoperazone and sulbactam (2 g, bid) (Anisodamine or atropine may be used for severe pain)	3 weeks	(2), (3), (4), (5), (6)
Chen (2023)[21]	China	35/35	T:47.20 ± 5.08 C:48.49 ± 5.24	Oral Sanhuang Pai Shi Soup (bid) + C	Oral UDCA (1 capsule, tid)	4 weeks	(1)(gallbladder wall thickness and gallbladder shrinkage rate), (2), (3), (4), (5), (6)

C = control group; CCK-A = serum cholecystokinin receptor; T = treatment group; UDCA = ursodeoxycholic acid; VIP = vasoactive intestinal peptide; (1), imaging improvement; (2), TC; (3), TBA; (4), TCM symptom scores; (5), total efectiveness rate; (6), occurrence of adverse reaction.

Table 2.

The frequency of the Chinese medicinal herbs.

No	Chinese medicinal herbs	Chinese medicinal herbs	Frequency
1	Rhei Radix et rhizoma	Dahuang	7
2	Scutellariae Radix	Huangqin	7
3	Lysimachiae Herba	Jinqiancao	7
4	Curcumae Radix	Yujin	7
5	Artemisiae Scopariae Herba	Yinchen	6
6	Bupleuri radix	Chaihu	5
7	Paeoniae Radix Alba	Baishao	4
8	Lygodii Spora	Haijinsha	4
9	Galli Gigerii Endothelium Corneum	Jineiji n	4
10	Citri Reticulatae Pericarpium Viride	Qingpi	4
11	Magnoliae Officinalis Cortex	Houpo	3
12	Gardeniae Fructus	Zhizi	3
13	Poria	Fuling	2
14	Glycyrrhizae Radix et Rhizoma	Gancao	2
15	Curcumae Longae Rhizoma	Jianghuang	2
16	Lonicerae Japonicae Flos	Jinyinhua	2
17	Natrii sulfas	Mangxiao	2
18	Aucklandiae radix	Muxiang	2
19	Sparganii Rhizoma	Sanleng	2
20	Clematidis Radix et Rhizoma	Weilingxian	2
21	Corydalis Rhizoma	Yemhusuo	2
22	Coicis Semen	Yiyiren	2

3.3. Assessment of the risk of bias

The quality of the 8 RCTs included was systematically assessed according to the quality assessment tools recommended by the Cochrane Manual. Seven studies that explicitly described the correct method for generating random sequences (random number table method) were rated as low risk. One study mentioned grouping by order of admission, which was rated as high risk. Because none of the RCTs mentioned allocation procedures and constraint methods, they were rated as ambiguous risks. Because of the absence of data flaws and the selection of favorable outcome reports, the integrity of all investigators’ results data and selective reporting were judged to be low-risk bias. However, no details of other biases were found in all the studies, which were rated as unclear risks (Figs. 2 and 3).

Figure 2.

Risk of bias graph. The quality of the 8 randomized controlled trials (RCTs) included was systematically assessed according to the quality assessment tools recommended by the Cochrane Manual. Seven studies that explicitly described the correct method for generating random sequences (random number table method) were rated as low risk. One study mentioned grouping by order of admission, which was rated as high risk. Because none of the RCTs mentioned allocation procedures and constraint methods, they were rated as ambiguous risks. Because of the absence of data flaws and the selection of favorable outcome reports, the integrity of all investigators’ results data and selective reporting were judged to be low-risk bias. However, no details of other biases were found in all the studies, which were rated as unclear risks.

Figure 3.

Risk of bias summary. The quality of the 8 randomized controlled trials (RCTs) included was systematically assessed according to the quality assessment tools recommended by the Cochrane Manual. Seven studies that explicitly described the correct method for generating random sequences (random number table method) were rated as low risk. One study mentioned grouping by order of admission, which was rated as high risk. Because none of the RCTs mentioned allocation procedures and constraint methods, they were rated as ambiguous risks. Because of the absence of data flaws and the selection of favorable outcome reports, the integrity of all investigators’ results data and selective reporting were judged to be low-risk bias. However, no details of other biases were found in all the studies, which were rated as unclear risks.

3.4. Meta-analysis results

3.4.1. Imaging improvement

A total of 5 RCTs studies^[15–18,21] reported imaging improvements, 3 of which^[15,17,18] described changes in gallstone diameter, 1^[16] described gallbladder emptying rate, and 1^[21] described gallbladder wall thickness, and gallbladder shrinkage. Among the 3 studies finally included,^[15,17,18] 2 of them^[17,18] used TCM + basic therapy + UDCA as the treatment group intervention, and 1 study^[15] used TCM + UDCA. There were 2 studies^[15,17] where the treatment group was treated for 2 months and 1 study^[18] for 8 weeks. As the duration of treatment and composition of Chinese medicines included in the studies were inconsistent, standardized MD were used. Due to the significant heterogeneity (P < .00001, I² = 93%), a random effects model was adopted. The results showed that the gallstone diameter of the Chinese medicine combined with the western medicine treatment group was significantly reduced (SMD = -1.51, 95% Cl (-2.36, -0.65), P < .001) (Fig. 4). A sensitivity analysis is required, which is done by excluding each study individually. Results show that heterogeneity has no obvious change, but it is worth noting that after eliminating the study^[17] of Liu, heterogeneity changed significantly (P = .29, I² = 18%). This shows that the imaging improvement of meta-analysis results lacks robustness, vulnerable to the research of the change of the number of significant changes (Table S2, Supplemental Digital Content, https://links.lww.com/MD/P284).

Figure 4.

Forest plot of the meta-analysis comparing the imaging improvement. A total of 5 randomized controlled trial studies^[15–18,21] reported imaging improvements, 3 of which^[15,17,18] described changes in gallstone diameter, 1^[16] described gallbladder emptying rate, and 1^[21] described gallbladder wall thickness and gallbladder shrinkage. Among the 3 studies finally included,^[15,17,18] 2 of them^[17,18] used TCM + basic therapy + UDCA as the treatment group intervention, and 1 study^[15] used TCM + UDCA. There were 2 studies^[15,17] where the treatment group was treated for 2 months and 1 study^[18] for 8 weeks. As the duration of treatment and composition of Chinese medicines included in the studies were inconsistent, standardized mean difference (SMD) were used. Due to the significant heterogeneity (P < .00001, I² = 93%), a random effects model was adopted. The results showed that the gallstone diameter of the Chinese medicine combined with the western medicine treatment group was significantly reduced (SMD = -1.51, 95% Cl (-2.36, -0.65), P < .001). A sensitivity analysis is required, which is done by excluding each study individually. Results show that heterogeneity has no obvious change, but it is worth noting that after eliminating the study^[17] of Liu, heterogeneity changed significantly (P = .29, I² = 18%). This shows that the imaging improvement of meta-analysis results lacks robustness, vulnerable to the research of the change of the number of significant changes (Table S2, Supplemental Digital Content, https://links.lww.com/MD/P284). TCM = traditional Chinese medicine.

3.4.2. TC

In the last 3 studies included,^[14,20,21] a heterogeneity test was conducted for the level of TC. The results indicated significant heterogeneity among the studies (P < .00001, I² = 95%), leading to the adoption of a stricter random effects model. Meta-analysis indicated a statistically significant difference in TC levels (SMD = -2.14, 95% Cl (-3.61, -0.67), P = .004) (Fig. 5). After excluding the study by Chen,^[21] there was a notable change in heterogeneity (P = .2, I² = 40%) according to sensitivity analysis presented in Table S3, Supplemental Digital Content, https://links.lww.com/MD/P285. This suggests that the meta-analysis results regarding TC levels lack robustness and are susceptible to significant changes due to alterations in the number of studies.

Figure 5.

Forest plot of the meta-analysis comparing the TC. In the last 3 studies included,^[14,20,21] a heterogeneity test was conducted for the level of TC. The results indicated significant heterogeneity among the studies (P < .00001, I² = 95%), leading to the adoption of a stricter random effects model. Meta-analysis indicated a statistically significant difference in TC levels (SMD = -2.14, 95% Cl (-3.61, -0.67), P = .004). After excluding the study by Chen,^[21] there was a notable change in heterogeneity (P = .2, I² = 40%) according to sensitivity analysis presented in Table S3, Supplemental Digital Content, https://links.lww.com/MD/P285. This suggests that the meta-analysis results regarding TC levels lack robustness and are susceptible to significant changes due to alterations in the number of studies. TC = total cholesterol.

3.4.3. TBA

The treatment group was divided into 3 studies.^[14,20,21] Heterogeneity inspection revealed significant heterogeneity in TBA levels among the studies (P < .00001, I² = 99%). Sensitivity analysis demonstrated that the association remained stable (see Table S4, Supplemental Digital Content, https://links.lww.com/MD/P286). Meta-analysis indicated a statistically significant difference in TBA levels (SMD = -0.97, 95% CI (−3.36, −1.42), P = .043) (Fig. 6).

Figure 6.

Forest plot of the meta-analysis comparing the TBA. The treatment group was divided into 3 studies.^[14,20,21] Heterogeneity inspection revealed significant heterogeneity in TBA levels among the studies (P < .00001, I² = 99%). Sensitivity analysis demonstrated that the association remained stable (see Table S4, Supplemental Digital Content, https://links.lww.com/MD/P286). Meta-analysis indicated a statistically significant difference in TBA levels (SMD = -0.97, 95% CI (−3.36, −1.42), P = .043). TBA = total bile acids.

3.4.4. TCM symptom scores

A total of 5 studies^[15,18–21] involving a total of 476 participants reported changes in TCM symptom scores, of which 2^[18,21] were not analyzed because they had only a single symptom score and no overall TCM symptom score. In the last 3 studies included,^[15,19–21] the heterogeneity test suggested that there was great heterogeneity among the studies (P < .00001, I² = 95%), so a random effects model was used. Results show that there is statistical significance (SMD = -1.88, 95% CI (−3.16, −0.60), P = .004) (Fig. 7). Sensitivity analysis showed that heterogeneity changed significantly (P = .1, I² = 63%) after exclusion of Zhao’s study.^[15] This suggests that the TCM symptom score of meta-analysis results lacks robustness (Table S5, Supplemental Digital Content, https://links.lww.com/MD/P287).

Figure 7.

Forest plot of the meta-analysis comparing the TCM symptom scores. A total of 5 studies^[15,18–21] involving a total of 476 participants reported changes in TCM symptom scores, of which 2^[18,21] were not analyzed because they had only a single symptom score and no overall TCM symptom score. In the last 3 studies included,^[15,19–21] the heterogeneity test suggested that there was great heterogeneity among the studies (P < .00001, I² = 95%), so a random effects model was used. Results show that there is statistical significance (SMD = −1.88, 95% CI (−3.16, −0.60), P = .004). Sensitivity analysis showed that heterogeneity changed significantly (P = .1, I² = 63%) after exclusion of Zhao’s study.^[15] This suggests that the TCM symptom score of meta-analysis results lacks robustness (Table S5, Supplemental Digital Content, https://links.lww.com/MD/P287). TCM = traditional Chinese medicine.

3.4.5. Occurrence of adverse reaction

A total of 463 participants in 4 studies reported^{[15,16,18,20]} the occurrence of adverse drug reactions, including dizziness, loose stools, rubella, diarrhea, nausea, and vomiting. The adverse drug reactions in the treatment group and the control group were mild and resolved without specific management measures. Three other studies^[14,19,21] reported no adverse effects and were not included in the analysis. The heterogeneity test showed that there was no significant heterogeneity among the studies (P = .97, I² = 0%), and the fixed effect model was used. The results showed that the difference was not statistically significant (OR = 0.51, 95% Cl (0.21, 1.24), P = .14) (Fig. 8), indicating that the combination of TCM and Western medicine did not increase the incidence of adverse reactions.

Figure 8.

Forest plot of the meta-analysis comparing the occurrence of adverse reaction. A total of 463 participants in 4 studies reported^{[15,16,18,20]} the occurrence of adverse drug reactions, including dizziness, loose stools, rubella, diarrhea, nausea, and vomiting. The adverse drug reactions in the treatment group and the control group were mild and resolved without specific management measures. Three other studies^[14,19,21] reported no adverse effects and were not included in the analysis. The heterogeneity test showed that there was no significant heterogeneity among the studies (P = .97, I² = 0%), and the fixed effect model was used. The results showed that the difference was not statistically significant (OR = 0.51, 95% CI (0.21, 1.24), P = .14), indicating that the combination of TCM and Western medicine did not increase the incidence of adverse reactions. TCM = traditional Chinese medicine.

4. Discussion

Due to the studies of a randomized clinical trial methodology quality is poorer, for patients with gallstones, and the effectiveness of TCM treatment is still controversial.^[23] In a previous meta-analysis,^[24] compared with the control group, the treatment of TCM can reduce bile gravel postoperative recurrence rate. In recent years, the number of randomized clinical trials of TCM in the treatment of gallstones has gradually increased. Therefore, this meta-analysis updated the literature, and further studied the combination of TCM and Western medicine in the treatment of gallstones, to explore a safer and more effective treatment method. A total of 8 articles with 912 patients were included in this meta-analysis. The imaging examination, blood analysis, and TCM symptom scores of the gallstone treatment group were better than those of the control group. There was no significant difference in adverse reactions between the treatment group and the control group. Meta-analysis results show that TCM as an adjuvant treatment for gallstones can more effectively dissolve gallstones,^[15,17,18] reduce cholesterol and improve bile acid,^[14,20,21] and effectively relieve symptoms such as right upper abdominal pain, right upper abdominal tenderness, nausea and vomiting, bitter mouth and dry throat, upper abdominal fullness, and abnormal stool.^[15,19,21] The symptoms of dizziness, loose stool, rubella, diarrhea, nausea, and vomiting were observed in a small number of cases treated with TCM combined with Western medicine, and there were no obvious side effects compared with conventional Western medicine.^{[15,16,18,20]} However, due to the quality of the included studies, the stability of the results of TC and TCM symptom scores was a concern, but the results of imaging tests, bile acid levels, and adverse effects were robust. This conclusion can provide a reference for the clinical use of this therapy.

Gallstones are caused by abnormal cholesterol bile acid and phospholipid levels,^[25] cholesterol is the main factor for the formation of gallstones,^[26] and bile acid levels gradually get the attention of scholars, and put forward the forecast as potential biomarkers of metabolites of gallstones.^[27] TCM compounds can improve biliary dynamics, maintain and protect the liver, lower cholesterol, and bilirubin levels, and adjust the role of inflammation, to regulate body function, and treatment of gallstones.^[28]In TCM, gallstones can be classified into “gallbladder distension,” “abdominal pain” and “jaundice.” Its etiology is mainly due to the abnormal function of the liver, the body’s qi machine block, depression, and heat, resulting in liver and gallbladder damp heat, heat back burning body, and biliary tract failure, so that the bile excretion is not smooth, long and fumigation, suffering into stone. Therefore, the treatment of gallstones should be based on the main principles of soothing the liver promoting the gallbladder, and clearing the damp heat.

According to the frequency statistics of Chinese herbs used in the 8 included studies, 34 Chinese herbs were obtained, and 22 herbs were used twice or more (Table 2). The frequencies of rhubarb, Scutellaria baicalensis, Lysimachia sinensis, Curcuma sinensis, and Artemisia sinensis were 6 or more times. The above 6 kinds of TCM soothe the liver and gallbladder, clearing the heat and dampness effect, in line with the principle of TCM treatment of gallstones. Rhei Radix et Rhizoma can regulate liver PPARα and SREBP target genes, PCSK9 and intestinal ABCG8 genes, and improve blood cholesterol transport, liver lipid metabolism, and intestinal cholesterol excretion.^[29] Scutellariae Radix has anti-inflammatory, immunosuppressive, and lipid metabolism regulation effects.^[30] Lysimachiae herba is the main drug for stone removal, and modern pharmacology believes that its active ingredients have the effects of cholelithiasis, anti-inflammatory and antibacterial.^[31] It can improve the clinical symptoms of patients with gallstones by increasing serum cholecystokinin receptor (CCK-A) and vasoactive intestinal peptide (VIP) levels.^[32] Curcumae radix has hepatoprotective, anti-inflammatory, and analgesic effects,^[33] which help to relieve the symptoms of abdominal pain. Wormwood (Artemisia Scopariae Herba) contains east hyoscyamus Niger ketone, capillary protein, chlorogenic acid, and representative bioactive ingredients such as flavonoids, cholagogue function, anti-oxidation, anti-inflammatory effect, which can help prevent cholestasis, treatment of gallstones.^[34]

We conducted a comprehensive literature search on the treatment of gallstones with TCM and standardized the inclusion and exclusion criteria for the literature. The administration of TCM was limited to oral intake, while the control group received Western medicine conservative treatment recommended by consensus as an intervention measure. This approach aimed to eliminate any potential influence from other treatment methods on the study results, ensuring greater authenticity and reliability. By consensus-recommended efficacy evaluation criteria, objective indicators such as imaging examination and blood analysis were adopted as primary outcome measures to enhance objectivity and realism. However, we still encounter the following limitations: (1) the current literature on RCTs of gallstone treatment with surgical intervention combining TCM and Western medicine is scarce and lacks high-quality evidence. The included articles in this study lacked detailed allocation concealment, blinding, and other biases, resulting in a low-quality evaluation of the literature and compromising the reliability and accuracy of the conclusions. 2. Since all the literature meeting our inclusion and exclusion criteria originated from China, with a study population consisting solely of Chinese individuals, there is a lack of relevant treatment literature for other populations which limits generalizability. 3. Due to the limited number of articles that met our inclusion and exclusion criteria, subgroup analysis and bias analysis could not be conducted, potentially introducing some bias into the results of our meta-analysis. 4. Insufficient follow-up reports prevent us from assessing whether combined TCM and Western medicine treatment for gallstones affects recurrence rates.

5. Conclusion

Chinese medicine combined with Western medicine may be better than Western medicine alone in the treatment of gallstones. However, due to the limited quantity and quality of the included literature, more literature on double-blind RCTs with large samples is needed in the later stage to verify this conclusion. To provide a reasonable and effective treatment plan for the clinical treatment of gallstones.

Acknowledgments

Gratitude is extended to Changchun University of Chinese Medicine for facilitating the literature resources for this study.

Author contributions

Software: Tianpei Jiang, Wensi Ouyang.

Supervision: Wenjie Yao.

Validation: Jiantong Dong.

Writing – original draft: Tianpei Jiang.

Writing – review & editing: Tianpei Jiang, Jinna Nie.