Danning tablets for the treatment of multiple gallbladder polyps: Study protocol of multicentre, randomised, open-labelled, controlled trial.

Tian Yang: Writing – review & editing, Writing – original draft, Supervision, Project administration, Investigation, Funding acquisition, Formal analysis, Conceptualization. Ming-Da Wang: Writing – original draft, Supervision, Software, Methodology, Investigation, Data curation, Conceptualization. Gui-Lin Xie: Visualization, Project administration, Methodology, Investigation, Formal analysis, Conceptualization. Xiong-Hua Wang: Software, Resources, Project administration, Methodology, Investigation, Formal analysis. Liu Zheng: Visualization, Validation, Software, Methodology, Data curation, Conceptualization. Li-Min Wang: Visualization, Validation, Supervision, Project administration, Investigation, Funding acquisition, Formal analysis, Conceptualization. Guang-Fa Xiao: Visualization, Validation, Supervision, Software, Resources, Formal analysis, Conceptualization. Yong-Qing Yang: Software, Resources, Methodology, Investigation, Funding acquisition, Data curation, Conceptualization. Chao Li: Validation, Software, Project administration, Methodology, Data curation. Alfred Wei Chieh Kow: Writing – review & editing, Visualization, Validation, Supervision, Software. Feng Shen: Writing – review & editing, Visualization, Validation, Supervision, Project administration, Funding acquisition, Conceptualization.

The Ethics Committee of Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China, approved the present study (approval no. EHBHKY-2022-H038-P001).

This study received funding from Shanghai Hutchison Pharmaceuticals Company. The funders was not involved in the study design, the writing of this article, or the decision to submit it for publication.

The primary aim of this study is to evaluate the efficacy and safety of Danning Tablets in the treatment of MGPs. Specifically, the study seeks to determine whether Danning Tablets, when used alongside standard care, can effectively reduce the size of MGPs and improve related symptoms. Additionally, the study aims to explore the potential impacts of this treatment on overall patient quality of life and satisfaction. Through this research, we intend to provide a comprehensive assessment of Danning Tablets as a viable non-surgical treatment option for patients with MGPs, potentially offering a significant advancement in the management of this condition. This multicentre, randomized, controlled, open-label trial is designed to rigorously evaluate the effectiveness of Danning Tablets in conjunction with standard care for treating MGPs, registered with the trial number NCT05668871 . The study will be conducted in phases over a 6-month period, with participants being randomly assigned to either the intervention group (receiving Danning Tablets plus standard care) or the control group (receiving standard care alone). The open-label nature of the trial acknowledges the practicalities of administering a traditional Chinese medicine intervention. The trial’ s methodology is structured to ensure robust data collection and analysis, providing reliable and scientifically sound results. A detailed flow diagram will be used to illustrate the trial’s structure, including participant recruitment, randomization, follow-up, and data analysis stages ( Fig. 1 ). This diagram will ensure clarity in the trial’s progression and will be an essential tool for both researchers and stakeholders to understand the study’s methodology and progression at a glance. Fig. 1 Flowchart of the implementation of the study protocol. Fig. 1 Flowchart of the implementation of the study protocol. The study is structured as a multicentre, randomised, open-label, controlled trial spanning at least 24 weeks of treatment for patients with MGPs. The trial setting is meticulously planned to ensure a rigorous evaluation of the efficacy and safety of Danning Tablets in treating MGPs. The study will involve multiple follow-up visits for participants at key intervals: baseline (in-person visit), and then follow-ups at the 4th week (telephone), 8th week (telephone), 12th week (in-person), and 24th week (in-person). These follow-up sessions are crucial for assessing the treatment’s impact on the size and symptoms of MGPs and monitoring any potential adverse effects. For the control group, a standard care regimen involving lifestyle intervention will be implemented. This approach serves as a comparator to evaluate the added benefit of Danning Tablets when combined with standard care practices. Using computer-generated randomized blocks, participants will be randomly allocated to either the Intervention group (receiving Danning Tablets) or the control group (receiving standard care) in a 1:1 ratio. Due to the nature of the intervention, blinding of participants and clinicians will not be possible. The study will involve adult patients diagnosed with MGPs. The inclusion and exclusion criteria for the participants are carefully defined to ensure the selection of a homogeneous and appropriate study population. The inclusion and exclusion criteria of this study are defined as follows: (1). Age and Gender: Adults aged 18–75 years, both male and female. (2). Diagnosis: Diagnosed with MGPs (≥2 polyps) based on ultrasound examinations within 2 weeks before enrolment. (3). Polyp Size: Largest polyps measuring between 3 mm and 7 mm in diameter. (4). Symptomatology: Participants with or without symptoms related to GPs, such as ventosity, nausea, anorexia, right upper abdominal pain, and right shoulder radiating pain, etc. (5). Informed Consent: Ability to understand and willingness to sign a written informed consent document. Age and Gender: Adults aged 18–75 years, both male and female. Diagnosis: Diagnosed with MGPs (≥2 polyps) based on ultrasound examinations within 2 weeks before enrolment. Polyp Size: Largest polyps measuring between 3 mm and 7 mm in diameter. Symptomatology: Participants with or without symptoms related to GPs, such as ventosity, nausea, anorexia, right upper abdominal pain, and right shoulder radiating pain, etc. Informed Consent: Ability to understand and willingness to sign a written informed consent document. (1). Clinical diagnosis of gallbladder cancer, and/or gallbladder/bile duct stones, and/or acute cholecystitis. (2). Previous gallbladder/biliary tract surgery, such as gallbladder-preserving cholecystolithotomy, lithotomy by endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC), etc. (3). Thickness of gallbladder wall >6 mm based on ultrasound examinations. (4). Severe comorbid conditions, including active severe infectious or severe primary cardiovascular, cerebrovascular, pulmonary, renal, endocrine, or hematopoietic disease, or with mental disorders and/or behavioural abnormalities. (5). Irregular stool and/or stool evacuation frequency ≥5 times/day within 2 weeks before enrolment. (6). Regularly taking any Chinese patent medicine (including TCM injection) with "soothing liver, cholagogic, clearing heat, dredging intestines" clearly written in the instructions, or regularly taking the TCM decoction with the effect of soothing liver and cholagogic within 4 weeks before enrolment. (7). Currently receiving other pharmacological treatments for MGPs. (8). Regularly taking proton pump inhibitors or H2-receptor antagonists cholinergic receptor antagonists or gastrin receptor antagonists within 4 weeks before enrolment. (9). Pregnancy or lactation: Women who are pregnant, planning to become pregnant, or breastfeeding. (10). Allergies: Participants with known hypersensitivity to any components of Danning Tablets. (11). Poor patient compliance or being unable to cooperate with the investigator. (12). Participation in another trial within 3 months before enrolment. (13). Any other situations not suitable for inclusion. Clinical diagnosis of gallbladder cancer, and/or gallbladder/bile duct stones, and/or acute cholecystitis. Previous gallbladder/biliary tract surgery, such as gallbladder-preserving cholecystolithotomy, lithotomy by endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC), etc. Thickness of gallbladder wall >6 mm based on ultrasound examinations. Severe comorbid conditions, including active severe infectious or severe primary cardiovascular, cerebrovascular, pulmonary, renal, endocrine, or hematopoietic disease, or with mental disorders and/or behavioural abnormalities. Irregular stool and/or stool evacuation frequency ≥5 times/day within 2 weeks before enrolment. Regularly taking any Chinese patent medicine (including TCM injection) with "soothing liver, cholagogic, clearing heat, dredging intestines" clearly written in the instructions, or regularly taking the TCM decoction with the effect of soothing liver and cholagogic within 4 weeks before enrolment. Currently receiving other pharmacological treatments for MGPs. Regularly taking proton pump inhibitors or H2-receptor antagonists cholinergic receptor antagonists or gastrin receptor antagonists within 4 weeks before enrolment. Pregnancy or lactation: Women who are pregnant, planning to become pregnant, or breastfeeding. Allergies: Participants with known hypersensitivity to any components of Danning Tablets. Poor patient compliance or being unable to cooperate with the investigator. Participation in another trial within 3 months before enrolment. Any other situations not suitable for inclusion. These criteria aim to ensure the safety of the participants and the validity of the study results by minimizing confounding factors and variability among participants. The intervention in this clinical trial involves the administration of Danning Tablets, a traditional Chinese medicine product (National Medicine Permit Number Z10910040, produced by Shanghai Hutchinson Pharmaceutical Co., Ltd.). The tablets are film-coated, brownish-black after removing the coating, and have a sweet and bitter taste. Each tablet is 0.36 g, containing ingredients from Radix et Rhizoma Rhei (Da Huang), Rhizoma et Radix Polygoni Cuspidati (Hu Zhang), Pericarpium Citri Reticulatae Viride (Qing Pi), Pericarpium Citri Reticulatae (Chen Pi), Fructus Crataegi (Shan Zha), Radix Curcumae (Yu Jin) and Rhizoma Imperatae (Bai Mao Gen). The administration protocol for the intervention group includes oral intake of Danning Tablets at a dosage of 5 tablets per time, three times daily, taken post meals. Danning Tablets will be provided from baseline (day 1) to week 12 ± 1 after randomization, followed by 12-week lifestyle intervention. Lifestyle intervention includes dietary advice to avoid cold, spicy, sour, and other irritating foods, abstain from smoking and alcohol, and to avoid excessive fatigue and emotional stress. A regular, low-fat, low-calorie diet is recommended, along with a consistent and timely eating schedule. The control group will receive standard care, which encompasses lifestyle intervention similar to the intervention group but without the addition of Danning Tablets from baseline (day 1) to week 24 ± 1 after randomization. This comparison aims to isolate the effect of Danning Tablets when combined with standard care in the treatment of MGPs. The study’s outcomes are strategically outlined to assess both the efficacy and safety of the treatment for MGPs. The primary and secondary outcomes are as follows. Clinical Efficacy at Week 24: The primary measure is the clinical efficacy rate at the 24th week following medication commencement. Efficacy is determined based on the proportion of patients who experience a reduction in the size of the largest polyp or complete polyp resolution, as assessed by ultrasound. A. Cure: Disappearance of polyps upon re-examination. B. Effective: Reduction in the maximum diameter of the largest polyp. C. Ineffective: No change or increase in the maximum diameter of the largest polyp. D. Clinical Efficacy Rate: Defined as the proportion of patients who are cured or show effectiveness (Cure + Effective) over the total number of patients. (1). Symptom Relief Rate: This rate evaluates the improvement in symptoms such as abdominal distension, nausea, anorexia, upper right abdominal pain, and radiating right shoulder pain. Improvement is measured using the Visual Analogue Scale (VAS) scores, with a decrease in score indicating symptom relief. (2). Disease Progression Rate: Assessed by the increase in the size of the largest polyp (≥2 mm in diameter), this rate helps to understand the progression of the condition in the patient population. (3). Incidence of Adverse Events/Reactions: Monitoring and reporting of any adverse events or reactions are crucial for evaluating the safety and tolerability of Danning Tablets. Symptom Relief Rate: This rate evaluates the improvement in symptoms such as abdominal distension, nausea, anorexia, upper right abdominal pain, and radiating right shoulder pain. Improvement is measured using the Visual Analogue Scale (VAS) scores, with a decrease in score indicating symptom relief. Disease Progression Rate: Assessed by the increase in the size of the largest polyp (≥2 mm in diameter), this rate helps to understand the progression of the condition in the patient population. Incidence of Adverse Events/Reactions: Monitoring and reporting of any adverse events or reactions are crucial for evaluating the safety and tolerability of Danning Tablets. These outcomes will provide a comprehensive understanding of the impact of Danning Tablets on MGPs, encompassing both the effectiveness of the treatment and the safety profile for patients. The sample size calculation for this multicentre, randomized, controlled, open-label trial is based on previous literature and assumptions about the efficacy rates of the treatment and control groups. The study aims to evaluate the effectiveness of Danning Tablets in treating MGPs compared to standard care over a 24-week period. Assumptions for the calculation include an estimated efficacy rate of 70% in the treatment group (receiving Danning Tablets) and 40% in the control group (receiving standard care). These estimates are based on the effectiveness of similar interventions reported in prior studies. The superiority margin is set at 0.15, with a type I error rate (α) of 0.05 and a power (1−β) of 0.8, to ensure adequate detection of a clinically meaningful difference between the two groups. Based on these parameters, the calculated sample size for each group is 132 participants. However, to account for an anticipated dropout rate of 20%, which is a common occurrence in clinical trials due to various reasons such as loss to follow-up, adverse events, or withdrawal of consent, the total sample size required for the study is increased to 336 participants. This adjustment ensures that the study maintains statistical power to detect the specified effect size despite potential participant attrition. For this study, participants will be randomly assigned to either the intervention group, receiving Danning Tablets in addition to standard care, or the control group, which will receive standard care alone. The randomization process will utilize a computer-generated random number table to ensure impartial and unbiased allocation of participants into each group. This task will be managed by an independent data coordinating centre to uphold the integrity of allocation concealment. The intervention group will receive oral administration of Danning Tablets, in addition to standard care. The dosage recommended for Danning Tablets is 5 tablets per administration, taken three times daily after meals. In contrast, the control group will adhere to standard care, which encompasses general lifestyle and dietary recommendations without the addition of Danning Tablets. Standard care includes advice on maintaining a healthy diet, avoiding alcohol and tobacco, and managing stress levels. Data will be collected at baseline and 4, 8, 12, and 24 weeks. Each assessment will include ultrasound examinations, symptom evaluations, quality-of-life questionnaires, and safety monitoring. Data will be managed using a secure, electronic data capture system, with access restricted to authorized study personnel. Data integrity will be ensured through regular audits. (1). Data Recording Methods: Data will be recorded meticulously and systematically using standardized forms across all participating centers. This includes clinical assessments, laboratory results, imaging findings, and patient-reported outcomes. (2). Researcher Data Entry Requirements: Researchers are responsible for accurate and complete data entry. They must adhere to the protocol and ensure that all relevant data points are captured in the Case Report Forms (CRFs) or electronic CRFs (e-CRFs). (3). Data collection management: A robust system will be in place for managing data collection, ensuring timely and accurate data capture, and minimizing missing data. (4). CRF/e-CRF Design: CRFs and e-CRFs will be designed to capture all necessary information in a user-friendly format, facilitating accurate and complete data entry. (5). Data Management Plan: The plan will outline procedures for data entry, verification, storage, and handling of data discrepancies. (6). Database Management: A secure, centralized database will be used for data storage, with restricted access to authorized personnel only. (7). Data Verification, Cleaning, and Quality Control: Regular data quality checks will be performed to identify and rectify any inconsistencies or errors in the dataset. (8). Data Review Meetings: Regular meetings will be held to review the data collected, discuss any issues, and ensure ongoing data quality. (9). Database Locking and Unlocking: The database will be locked for analysis at the end of the study, following a final review and cleaning of the data. (10). Visit-Specific Data Collection: ① Visit 1: Screening + Baseline: Data collection at this stage will include demographic information, medical history, diagnosis of MGPs, baseline measurements, and baseline symptom assessment. ② Visit 2 and 3: Telephone Follow-up: These visits will involve telephone interviews to assess ongoing symptoms, treatment adherence, and any adverse events. ③ Visit 4 and 5: In-person Follow-up: These visits will include physical examinations, repeat imaging studies to assess the change in polyp size, and additional laboratory tests as needed. Data Recording Methods: Data will be recorded meticulously and systematically using standardized forms across all participating centers. This includes clinical assessments, laboratory results, imaging findings, and patient-reported outcomes. Researcher Data Entry Requirements: Researchers are responsible for accurate and complete data entry. They must adhere to the protocol and ensure that all relevant data points are captured in the Case Report Forms (CRFs) or electronic CRFs (e-CRFs). Data collection management: A robust system will be in place for managing data collection, ensuring timely and accurate data capture, and minimizing missing data. CRF/e-CRF Design: CRFs and e-CRFs will be designed to capture all necessary information in a user-friendly format, facilitating accurate and complete data entry. Data Management Plan: The plan will outline procedures for data entry, verification, storage, and handling of data discrepancies. Database Management: A secure, centralized database will be used for data storage, with restricted access to authorized personnel only. Data Verification, Cleaning, and Quality Control: Regular data quality checks will be performed to identify and rectify any inconsistencies or errors in the dataset. Data Review Meetings: Regular meetings will be held to review the data collected, discuss any issues, and ensure ongoing data quality. Database Locking and Unlocking: The database will be locked for analysis at the end of the study, following a final review and cleaning of the data. Visit-Specific Data Collection: ① Visit 1: Screening + Baseline: Data collection at this stage will include demographic information, medical history, diagnosis of MGPs, baseline measurements, and baseline symptom assessment. ② Visit 2 and 3: Telephone Follow-up: These visits will involve telephone interviews to assess ongoing symptoms, treatment adherence, and any adverse events. ③ Visit 4 and 5: In-person Follow-up: These visits will include physical examinations, repeat imaging studies to assess the change in polyp size, and additional laboratory tests as needed. Quality control measures include regular training of study staff, calibration of ultrasound equipment, and standardization of data collection procedures across all sites. The trial will adhere to Good Clinical Practice guidelines and local regulatory requirements. The statistical analysis for this randomized controlled trial will be comprehensive and robust, ensuring a thorough evaluation of the efficacy and safety of Danning Tablets in treating MGPs. The analysis will be conducted on an intention-to-treat basis, which includes all randomized participants in the groups to which they were originally assigned, regardless of their adherence to the treatment protocol. This approach enhances the generalizability of the study findings. Continuous variables, such as the size of GPs and quality of life scores, will be compared using independent t -tests or Mann–Whitney U tests, depending on the distribution of the data. Categorical variables, including the incidence of adverse events and treatment response rates, will be analysed using chi-square tests or Fisher’s exact tests, as appropriate. Subgroup analyses will be performed to explore potential differences in treatment effects based on baseline characteristics, such as the initial size of polyps, age, and gender of participants. This will help in identifying any specific patient populations that may benefit more from the treatment. Regression analyses will be utilized to adjust for potential confounders and to explore the relationship between treatment effects and covariates. The significance level will be set at a two-sided p -value of less than 0.05. The study will also employ sensitivity analyses to assess the robustness of the results, especially in handling missing data, which is a common challenge in clinical trials. All statistical analyses will be conducted using established statistical software, ensuring accuracy and reliability of the results. The comprehensive nature of the statistical analysis plan will ensure that the study conclusions are well-supported by the data. Ethical considerations and data dissemination are critical aspects of this study: (1). Ethics Committee and Institutional Review Board (EC/IRB): The study protocol has been reviewed and approved by the Ethics Committee or Institutional Review Board of each participating centre, ensuring compliance with ethical standards in clinical research. (2). Research Ethics: The study will adhere to the highest standards of research ethics, respecting the rights and welfare of all participants. This includes maintaining confidentiality and ensuring informed consent. (3). Research Protocol: The research protocol outlines all aspects of the study, ensuring transparency and adherence to ethical guidelines. (4). Participant Data Protection: Strict measures will be in place to protect the data and privacy of participants, in line with applicable data protection regulations. (5). Ethical and Regulatory Review: Regular reviews will be conducted to ensure ongoing compliance with ethical and regulatory standards. (6). Informed Consent: Participants will be provided with detailed information about the study and written informed consent will be obtained before enrolment. (7). Protocol and Consent Form Amendments: Any changes to the study protocol or consent forms will be documented and approved by the relevant EC/IRB. (8). Confidentiality: Participant confidentiality will be maintained throughout the study, with data being anonymized and securely stored. (9). Quality Control and Assurance: The study will implement stringent quality control and assurance measures to ensure the accuracy and reliability of the data. (10). Data Use and Publication: The findings of the study will be disseminated through peer-reviewed publications and presentations at scientific conferences, contributing to the body of knowledge on the treatment of MGPs with Danning Tablets. Ethics Committee and Institutional Review Board (EC/IRB): The study protocol has been reviewed and approved by the Ethics Committee or Institutional Review Board of each participating centre, ensuring compliance with ethical standards in clinical research. Research Ethics: The study will adhere to the highest standards of research ethics, respecting the rights and welfare of all participants. This includes maintaining confidentiality and ensuring informed consent. Research Protocol: The research protocol outlines all aspects of the study, ensuring transparency and adherence to ethical guidelines. Participant Data Protection: Strict measures will be in place to protect the data and privacy of participants, in line with applicable data protection regulations. Ethical and Regulatory Review: Regular reviews will be conducted to ensure ongoing compliance with ethical and regulatory standards. Informed Consent: Participants will be provided with detailed information about the study and written informed consent will be obtained before enrolment. Protocol and Consent Form Amendments: Any changes to the study protocol or consent forms will be documented and approved by the relevant EC/IRB. Confidentiality: Participant confidentiality will be maintained throughout the study, with data being anonymized and securely stored. Quality Control and Assurance: The study will implement stringent quality control and assurance measures to ensure the accuracy and reliability of the data. Data Use and Publication: The findings of the study will be disseminated through peer-reviewed publications and presentations at scientific conferences, contributing to the body of knowledge on the treatment of MGPs with Danning Tablets. Patients with a history of MGPs will play a crucial role in providing insights and feedback on the study design, particularly regarding the intervention procedures, outcome measures, and the overall feasibility of the study protocol. Their experiences and perspectives will help tailor the study to better meet the needs and concerns of those it aims to benefit. Additionally, public involvement, including patient advocacy groups and community healthcare stakeholders, will be sought to ensure broader community engagement and awareness about the study. This collaboration will aid in disseminating information about the study, recruiting participants, and ensuring the study’s relevance and acceptability to the wider public. Engaging patients and the public in this research process is fundamental to enhancing the study’s validity, ensuring better adherence to the treatment regimen, and improving the overall quality and impact of the research outcomes.

The study protocol will be conducted following The Helsinki Declaration. Written informed consent will be obtained from the participants. The results of the research will be disseminated through peer-reviewed publications. The trial registration number is NCT05668871 .

This study on the efficacy of Danning Tablets for treating MGPs represents a critical step in the evolution of GPs management. It holds the potential not only to improve patient outcomes but also to contribute valuable insights into the integration of traditional Chinese medicine in modern clinical practice. The findings from this study could have far-reaching implications, influencing future research directions, clinical practices, and patient care strategies in the field of gastroenterology and hepatology.

The study on the efficacy of Danning Tablets for the treatment of MGPs presents a significant advancement in the approach to managing a condition that affects a considerable portion of the population, particularly in countries like China [ 13 ]. The discussion of this study’s protocol addresses the rationale, potential implications, challenges, and the broader context of the research. MGPs, while often benign, can cause significant distress and have a potential risk of malignant transformation. The current standard management, involving surgical interventions, presents risks and psychological burdens for patients. Danning Tablets, rooted in traditional Chinese medicine, offer a novel non-surgical approach. Their use in this study is based on their reported efficacy in reducing the size of GPs and improving associated symptoms, backed by their anti-inflammatory and antitumor properties [ 14 ]. This study aims to provide rigorous clinical evidence for these observations. Should the trial demonstrate positive outcomes, it could revolutionize the treatment paradigm for MGPs. A shift towards a non-surgical, pharmacological approach could reduce the need for invasive procedures, minimize associated risks [ 15 ], and improve patient quality of life. Moreover, the study’s findings could open avenues for further research into traditional Chinese medicine formulations, bridging the gap between alternative and conventional medical practices. The open-label design of the study, while practical for a traditional medicine trial, could introduce biases. Measures such as rigorous data collection and analysis protocols are in place to mitigate this. Patient adherence to the treatment regimen is another potential challenge, emphasizing the need for clear patient education and regular follow-up. Additionally, the multifactorial nature of MGPs necessitates a comprehensive approach to treatment, considering lifestyle and dietary factors alongside medication. This study contributes to a growing body of research focusing on integrative medicine. It underscores the importance of exploring diverse treatment modalities, particularly in conditions where conventional treatments have limitations. The study aligns with the broader move towards patient-centred care, emphasizing treatments that align with patients’ preferences and reduce treatment burdens. The outcomes of this study could pave the way for further research into the long-term effects of Danning Tablets, their potential use in other gallbladder conditions, and a deeper exploration of the mechanisms behind their efficacy. Collaborative studies involving different regions and demographics could provide a more comprehensive understanding of the treatment’s effectiveness across diverse populations.

Gallbladder polyps (GPs) are a significant clinical entity due to their global prevalence and potential health implications [ 1 ]. These lesions, which protrude into the gallbladder cavity, vary in incidence, with rates ranging from 4.5% to 8.6% in China to 3.0%–6.0% in other countries [ 2 ]. The demographic most affected includes individuals over 40, particularly those with obesity, high blood lipids, fatty liver, or a history of chronic liver disease [ 3 ]. The symptoms of gallstone pancreatitis can range from being asymptomatic to causing significant discomfort, often aggravated when gallstones are present [ 4 ]. The rise in asymptomatic cases detected is attributed to the increased use of routine ultrasound screenings [ 5 ]. The complexity of GPs’ aetiology involves multiple factors, making their classification into single or multiple ones crucial for effective management [ 4 ]. Pseudo-GPs, encompassing cholesterol polyps, adenomyosis, inflammatory polyps, and proliferative polyps, constitute the majority, with cholesterol polyps being the most common [ 4 ]. True GPs, on the other hand, include benign tumours and early-stage gallbladder cancer [ 4 , 6 ]. The diverse nature and complex aetiology of GPs necessitate a thorough understanding of their epidemiology and potential health risks, setting the stage for targeted research and management strategies. The primary goal in treating GPs is to resolve the condition while minimizing potential complications [ 4 , 7 ]. Surgical interventions, like laparoscopic or open cholecystectomy, are recommended based on specific criteria but entail surgical risks and can impact digestive efficiency. Non-surgical approaches, including lifestyle modifications, medication, and regular monitoring, play a critical role in managing benign polyps and detecting malignancies early [ 7 ]. Continual surveillance, while challenging, offers the advantage of preserving gallbladder function and managing the uncertainty of disease progression. However, as GPs gradually enlarge or increase, it does increase the risk of symptoms and gallbladder cancer, which can increase the psychological burden on patients. In the realm of GPs, multiple gallbladder polyps (MGPs) hold a particular interest. Predominantly composed of cholesterol polyps, MGPs represent a subset of GPs where the risk of malignant transformation is generally low, yet their prevalence and symptomatic impact warrant careful attention [ 8 ]. The potential of these cholesterol polyps to respond positively to lifestyle modifications and pharmacological interventions presents an opportunity for innovative management strategies. The exploration of Traditional Chinese Medicine (TCM) in treating MGPs offers a new perspective. Danning Tablets, a TCM formulation comprising ingredients such as Radix et Rhizoma Rhei (Da Huang) , Rhizoma et Radix Polygoni Cuspidati (Hu Zhang), Pericarpium Citri Reticulatae Viride (Qing Pi), Pericarpium Citri Reticulatae (Chen Pi), Fructus Crataegi (Shan Zha), Radix Curcumae (Yu Jin) and Rhizoma Imperatae (Bai Mao Gen), have demonstrated hepatoprotective and anti-inflammatory effects [ 9 ]. A total of 32 constituents, including 14 anthraquinones and their glucosides, four anthrones, two naphthalene glycosides, two stilbenes and 10 flavonoids were identified [ 10 ]. The hepatoprotective efficacy of Danning tablets was reported in animal models, where the presence of emodin significantly amplifies bile flow impeded by alpha-thiocyanate quinone in rats [ 11 ]. Notably, it intervenes to ameliorate the heightened levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (γ-GTP), and alkaline phosphatase (ALP) activities induced in rat serum by α-naphthylisothiocyanate treatment [ 11 , 12 ]. Furthermore, the tablets exhibit the capacity to rectify aberrant levels of total bilirubin (TBiL), direct bilirubin (DBiL), and total bile acids (TBA). The anti-inflammatory effects are discerned in liver and gallbladder tissues through meticulous pathological and electron microscopy examinations. Danning tablets augment the phagocytic activity with gallbladder inflammation, concurrently elevating the count of dark cells in the bile epithelium. This augmentation serves to enhance the functionality of the gallbladder epithelium, thereby facilitating the restoration of fundamental functions in gallbladder epithelial cells [ 11 , 12 ]. Consequently, this process alleviates the inflammatory response within the gallbladders of affected rats. Previous studies have shown its effectiveness in alleviating gallbladder disease symptoms. For instance, Ding et al. proved that Danning Tablets could alleviate bile stasis induced by α-naphthylisothiocyanate by regulating the expression of transporters and metabolic enzymes [ 9 ]. Given that Danning Tablets could activate the farnesoid X receptor and promote bilirubin elimination through the regulation of the expression of liver and kidney transporters and the link between bilirubin accumulation and GPs, we hypothesize that Danning Tablets may influence GPs, particularly MGPs, by modulating lipid metabolism and reducing inflammation, potentially leading to a decrease in polyp size. This study aims to investigate the efficacy of Danning Tablets, combined with standard care, in treating MGPs. By focusing on this specific group, the research seeks to explore whether this combined treatment approach can effectively reduce the polyp size and improve patient symptoms, thereby contributing to the development of innovative, non-surgical treatment options for MGPs.

Tian Yang, Gui-Lin Xie, Xiong-Hua Wang, Liu Zheng, Li-Min Wang, Guang-Fa Xiao, and Yong-Qing Yang receive consulting fees and grants funding from Shanghai H&H Pharmaceutical Company. Tian Yang is the Executive Editor of the journal but was not involved in the peer review of this article or its editorial decision.The other authors declare no conflicts of interest.

Data available on request from the authors.