Published online Jun 19, 2026. doi: 10.5498/wjp.v16.i6.113229
Revised: November 18, 2025
Accepted: February 2, 2026
Published online: June 19, 2026
Processing time: 247 Days and 1.6 Hours
Conventional treatments for thyroid nodules (TNs), whether based on Western medicine or limited to emotional regulation, diet, and lifestyle adjustments, have shown modest effectiveness.
To evaluate the efficacy of Jianpi Huazhuo Xiaoying Decoction (JPHZXYD), a for
A total of 123 patients with TNs (January 2023 to November 2024) were enrolled and divided into two groups: A control group (n = 60) receiving conventional no
Compared with both baseline measurements and the control group, the observation group showed significant reductions in traditional Chinese medicine symptom scores, pulsatility index, resistance index, thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody levels. Patients in the observation group also experienced greater improvements in anxiety and depression, higher overall treatment effectiveness, and more pronounced reductions in TN diameter, number, and microvascular density, along with greater posttreatment in
JPHZXYD combined with emotional conditioning therapy enhances therapeutic efficacy and alleviates anxiety and depression in patients with TNs.
Core Tip: A total of 123 patients diagnosed with thyroid nodules (TNs) were selected to analyze the clinical effects of Jianpi Huazhuo Xiaoying Decoction combined with emotional conditioning and standardized life interventions (emotional guidance + dietary adjustments + daily routine modifications). The combined treatment alleviated clinical symptoms and negative emotions, improved efficacy, reduced the number and average diameter of TNs, lowered microvascular density, and improved thyroid function. These findings support its use as a valuable therapeutic strategy for managing TNs.
- Citation: Deng J, Zhang C, Xiao YX, Wang L. Jianpi Huazhuo Xiaoying Decoction plus emotional conditioning for thyroid nodule treatment: Impact on treatment outcomes and anxiety/depression. World J Psychiatry 2026; 16(6): 113229
- URL: https://www.wjgnet.com/2220-3206/full/v16/i6/113229.htm
- DOI: https://dx.doi.org/10.5498/wjp.v16.i6.113229
Thyroid nodules (TNs) are abnormal growths confined to the thyroid gland, showing distinct structural characteristics and echogenicities from the surrounding parenchymal tissue[1]. They are a common clinical condition, with a 67% incidence, a female predominance, and a 5% malignancy probability[2,3]. TN occurrence is linked to an irregular diet, sleep disturbances, alcoholism, smoking, physically demanding labor, obesity, and dyslipidemia[4]. Due to the absence of obvious clinical symptoms, only 5% of palpable TNs are clinically detected. Common clinical manifestations include neck lumps, chest tightness/pain, mood disorders, or even breathing difficulties and swallowing disorders[5]. Pathologically, chronic inflammation could induce a systemic inflammatory response by excessively inducing inflammatory factor release, thereby causing non-specific immune reactions that further aggravate TNs and related tumors[6]. Traditional Chinese medicine (TCM) attributes this condition to emotional dysregulation. The pathogenesis mainly involves spleen dysfunction, liver qi stagnation, and phlegm-blood stasis accumulation[7]. Therefore, TCM treatment resorts to spleen function enhancement to eliminate turbidity, phlegm dissipation, and mass resolution when managing TNs[7]. TCM herbal decoctions, independently or integrated with Western medicine, have been repeatedly documented to shrink TNs’ maximum diameters with certain safety profiles[8,9]. The present study applies the TCM formula Jianpi Huazhuo Xiaoying Decoction (JPHZXYD) for the treatment of patients with TNs. This formula comprises Fritillaria thunbergii (Zhe Bei Mu), Sparganium rhizome (San Leng), Curcuma rhizome (E Zhu), Bupleurum root (Chai Hu), Sinapis alba (Bai Jie Zi), Hedyotis diffusa (Bai Hua She She Cao), Rehmannia glutinosa (Sheng Di), Curcuma aromatica (Yu Jin), Atractylodes macrocephala (Bai Zhu), Oyster shell (Mu Li), Pinellia ternata (Ban Xia), Sargassum (Hai Zao), Pumice (Hai Fu Shi), Prunella vulgaris (Xia Ku Cao), and Astragalus membranaceus (Huang Qi). When prepared as a decoction, JPHZXYD can eliminate goiter, disperse nodules, resolve turbidity, and tonify the spleen[10].
Conventional treatments for TNs, whether involving Western medical interventions or limited to psychological, dietary, and lifestyle adjustments, remain relatively ineffective. To enhance treatment efficacy, this study applies a TCM perspective to compare JPHZXYD combined with emotional conditioning therapy against lifestyle interventions (dietary, emotional, and routine adjustments) alone. Given the scarcity of prior research, this study may help expand the application of JPHZXYD in TN management.
Eligibility criteria: Participants met the diagnostic criteria for TNs according to Western medical guidelines[11] and had at least one solid, cystic, or mixed (partially cystic) nodule confirmed by thyroid ultrasonography. All nodules were benign, as verified by fine-needle aspiration biopsy for those with suspicious malignant features. Eligible participants were adults aged 18 years or older who exhibited the TCM pattern of “phlegm-dampness with blood stasis syndrome”. Primary manifestations included palpable, firm neck nodules; limb heaviness or fatigue; and chest tightness or stabbing pain[12]. Secondary signs included neck swelling, occasional suffocation or stinging sensations, limb aching or distension, and dark-purple menstrual flow with blood clots. The tongue was dark with a sticky coating, and the pulse was stringy and slippery. Complete clinical records were required for inclusion.
Exclusion criteria: Patients were excluded if they had severe thyroiditis, metastatic thyroid cancer, or thyroid dysfunction; were pregnant or breastfeeding; had constipation secondary to organic lesions; exhibited intolerance to herbal medicine; required surgery due to tracheal compression or hoarseness; or had communication disorders resulting from psychiatric or cognitive conditions. A total of 123 eligible patients with TN were enrolled from Sichuan Provincial People’s Hospital between January 2023 and November 2024. Grouping was performed based on the different actual treatment plans received: A control group (n = 60; receiving lifestyle adjustments, like emotional regulation, dietary guidance, and daily routine management), and an observation group (n = 63; additionally administered JPHZXYD plus emotional conditioning). No significant baseline discrepancies were observed (P > 0.05), validating comparability of the study groups. Figure 1 presents the flowchart for patient screening based on the inclusion and exclusion requirements. This retrospective, nonrandomized controlled study strictly adhered to the Transparent Reporting of Evaluations with Nonrandomized Designs reporting guidelines.
Controls were intervened by a 28-day standardized lifestyle intervention protocol. This plan was jointly developed by endocrinologists, TCM practitioners, and nutritionists, from the aspects of emotional regulation, dietary guidance, and daily routine management. Through means such as distributing health education brochures and implementing regular follow-ups, patient compliance was reinforced.
Emotional regulation: A group health lecture was held once a week, lasting for 30 minutes each time. During these sessions, patients were informed about the basic knowledge of TNs, their benign nature, and generally favorable prognosis, thus reducing their anxiety and fear. They were encouraged to perform progressive muscle relaxation training or abdominal breathing exercises (15 minutes each, morning and evening). Guidance on attention diversion through listening to music, reading, socializing, etc., was provided to patients to help them maintain a cheerful mood.
Dietary guidance: Iodized salt was clearly advised, and selenium-rich foods (e.g., mushrooms, eggs, and lean meat) were encouraged, while high-iodine seafood (e.g., kelp, seaweed, and nori) was avoided, so as to support thyroid function. Following the “invigorating spleen for eliminating dampness and softening hardness for dispersing nodules” principle, patients were recommended to increase the intake of yams, Semen Coicis, white radish, and the like, while avoiding foods that are greasy, sweet, richly flavored, raw, cold, spicy, or stimulating.
Daily routine and exercise intervention: A personalized schedule was set for the patients, strictly requiring them to go to bed before 23:00 every night to ensure 7-8 hours of adequate sleep each day. They were instructed to engage in 3-5 sessions of moderate-intensity aerobic exercise (brisk walking, Tai Chi, Baduanjin, etc.) each week, for 30 minutes to 40 minutes per session. During the exercise, the heart rate was supposed to be (170 - age) beats per minute or slightly higher, with sweating slightly and not feeling tired as the criteria.
Besides the above interventions, patients in the observation group were administered JPHZXYD. The prescription included the following ingredients: Fritillaria thunbergii (10 g), Sparganium rhizome (10 g), Curcuma rhizome (15 g), Bupleurum root (15 g), Sinapis alba (9 g), Hedyotis diffusa (20 g), Rehmannia glutinosa (20 g), Curcuma aromatica (20 g), Atractylodes macrocephala (20 g), Oyster shell (20 g), Pinellia ternata (15 g), Sargassum (30 g), Pumice (30 g), Prunella vulgaris (20 g), and Astragalus membranaceus granules (40 g). A dose was boiled per day, to be taken in the morning and evening. A 28-day treatment course was implemented.
TCM syndrome score[13]: All participants underwent pre- and post-treatment TCM syndrome scoring regarding mass size, chest tightness or pain, and emotional irregularities. Each item scores 0-4, with worsening conditions indicated by elevated scores.
Anxiety and depression[14]: The evaluation was made pre- and post-treatment using the Self-Rating Anxiety (SAS) and Depression Scale (SDS). Each tool contains 20 items rated on a 4-point scale, with the standard score obtained by multiplying the total rough score by 1.25 and taking the integer part. Standard scores below 50 and 53 indicated anxiety and depression, respectively, with higher scores reflecting greater severity
Treatment effectiveness[15]: A treatment outcome was considered markedly effective if the patient achieved complete symptom resolution with a reduction in TN size exceeding two-thirds. An outcome was considered effective if there was significant symptom improvement with a reduction in TN size of between one-third and two-thirds. An outcome was considered ineffective if no improvement in symptoms or TN size was observed after treatment.
TN parameters and hemodynamics: A four-dimensional color Doppler ultrasound system was used to assess TN number, maximum diameter, microvascular density, and hemodynamic indices, including the pulsatility index (PI) and resistance index (RI), before and after treatment.
Thyroid function tests: Venous blood samples (5 mL) were collected at baseline and after treatment. Serum was separated by centrifugation and analyzed for free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels using automated immunoassays.
Thyroid autoantibodies: Thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were measured using Abbott’s chemiluminescent microparticle immunoassay method. To ensure objectivity, this study employed a blinded design for both the outcome evaluators and data analysts, who were kept unaware of group assignments to minimize measurement and confirmation biases.
All statistical analyses were performed using SPSS version 27.0. Categorical variables are presented as n (%), and continuous variables are presented as the mean ± SD (normally distributed) or the median (interquartile range; non-normally distributed). Categorical data were compared using the χ2 test, and continuous data were analyzed using the independent-samples t-test (between groups) and the paired t-test (within groups, before and after treatment) when a normal distribution was followed; the comparison for those violating the normality assumption was made using the Mann-Whitney U test. A P value < 0.05 was considered statistically significant. To evaluate the adequacy of the sample size, a post hoc power analysis was conducted using the primary efficacy outcome (total treatment effectiveness rate). The effective rate was 70.00% in the control group and 87.30% in the observation group. With α = 0.05 (two-tailed), PASS software was used to calculate the statistical power for comparing two independent proportions. The power (1 - β) under the current sample size was indicated to be > 90%; this suggests the capacity of the current sample size to detect an inter-group difference of approximately 17.3% in efficacy with a high degree of confidence, supporting the reliability of the statistical conclusions.
The study cohorts were comparable in female proportion, age, disease duration, tobacco/alcohol use history, and family medical history (P > 0.05; Table 1).
| Indicator | Control group (n = 60) | Observation group (n = 63) | χ2/t/Z | P value |
| Female count | 42 (70.00) | 38 (60.32) | 1.267 | 0.260 |
| Age (years) | 44.53 ± 8.74 | 46.40 ± 8.80 | 1.182 | 0.240 |
| Illness duration (months) | 10.00 (7.25, 12.00) | 10.00 (9.00, 12.00) | -1.246 | 0.213 |
| Smoking history | 22 (36.67) | 30 (47.62) | 1.511 | 0.219 |
| Alcoholism history | 18 (30.00) | 15 (23.81) | 0.600 | 0.439 |
| Familial medical history | 6 (10.00) | 5 (7.94) | 0.161 | 0.689 |
This study used TCM syndrome scores to detect changes in mass dimensions, chest oppression/pain, and mood irregularities. In the two groups, baseline scores were equivalent across domains (P > 0.05). The intervention caused marked score reductions across the cohorts, with the treatment used in the observation group leading to greater improvements (P < 0.05; Table 2).
| Indicator | Control group (n = 60) | Observation group (n = 63) | Z | P value |
| Mass dimension | ||||
| Pre-treatment | 4.00 (3.00, 4.00) | 3.00 (3.00, 4.00) | -1.267 | 0.205 |
| Post-treatment | 1.00 (1.00, 2.00)a | 1.00 (0.00, 1.00)b | -4.546 | < 0.001 |
| Chest oppression/pain | ||||
| Pre-treatment | 3.00 (3.00, 4.00) | 3.00 (3.00, 4.00) | -1.117 | 0.264 |
| Post-treatment | 2.00 (2.00, 3.00)a | 1.00 (0.00, 2.00)b | -6.582 | < 0.001 |
| Mood irregularities | ||||
| Pre-treatment | 3.00 (3.00, 4.00) | 3.00 (3.00, 4.00) | -1.093 | 0.274 |
| Post-treatment | 2.00 (1.00, 2.00)a | 1.00 (0.00, 1.00)b | -5.275 | < 0.001 |
Changes in anxiety (SAS) and depression (SDS) pre- and post-treatment were identified. Baseline scores differed insignificantly between groups (P > 0.05). Following the treatment, this study identified marked SAS and SDS score reductions across groups, with lower scores in the observation group vs controls (P < 0.05; Table 3).
Significantly greater effective cases and a higher total effectiveness rate were found in the observation group compared to controls (P < 0.05; Table 4).
| Indicator | Control group (n = 60) | Observation group (n = 63) | χ2 | P value |
| Markedly effective | 22 (36.67) | 30 (47.62) | ||
| Effective | 20 (33.33) | 25 (39.68) | ||
| Ineffective | 18 (30.00) | 8 (12.70) | ||
| Overall effectiveness | 42 (70.00) | 55 (87.30) | 5.519 | 0.019 |
TN parameters: Compared to controls, the observation group had fewer TNs, smaller average TN diameters, and lower microvessel densities (P < 0.05; Table 5).
| Indicator | Control group (n = 60) | Observation group (n = 63) | t/Z | P value |
| Number of nodules | 1.00 (1.00, 2.00) | 1.00 (1.00, 1.00) | -3.636 | < 0.001 |
| Average nodule diameter | 14.78 ± 3.22 | 8.65 ± 2.46 | 11.899 | < 0.001 |
| Microvascular density | 46.57 ± 8.46 | 37.83 ± 5.76 | 6.726 | < 0.001 |
PI and RI: The two groups were similar in PI and RI before treatment initiation (P > 0.05). Significant PI and RI reductions occurred in both groups post-intervention, particularly in the observation group (P < 0.05; Figure 2).
Thyroid function analysis: FT3, FT4, and TSH measurements were conducted to assess thyroid function. No significant intergroup differences were found at baseline (P > 0.05). In the control group, FT3 changed little after therapy (P > 0.05), whereas FT4 increased and TSH decreased (P < 0.05). An obvious post-treatment rise in FT3 and FT4 was noted in the observation group, accompanied by a reduction in TSH. The inter-group comparison showed lower TSH levels, as well as higher FT3 and FT4 levels, in the observation group vs controls after treatment (P < 0.05; Figure 3).
Thyroid autoantibodies: TPOAb and TgAb levels were determined to understand patients’ thyroid autoantibody levels. Baseline values were comparable (P > 0.05). Both antibodies decreased post-treatment (P < 0.05), with the observation group exhibiting lower posttreatment levels than controls (P < 0.05; Figure 4).
TCM holds that TN formation is driven by qi stagnation, phlegm accumulation, and blood stasis. Patients exhibit varied manifestations at different stages of their illness. In the early stage, they mostly present with phlegm congestion and qi stagnation. During the middle stage, phlegm-dampness and blood stasis obstruction are dominant. The intertwining phlegm and stasis is the major later-stage presentation[16]. Emotional conditioning is therefore crucial. Helping patients build a positive, optimistic, and relaxed mindset is conducive to relieving excessive life pressures, thereby aiding in soothing the liver and regulating qi to reverse disease progression[17]. For efficacy enhancement, this study supplemented JPHZXYD for intervention. In this formula, Astragalus membranaceus and Atractylodes macrocephala exert spleen-tonifying and qi-boosting activities to promote dampness transformation and phlegm-turbidity alleviation[18]. The intermingled phlegm and stasis are resolved by the combined use of Fritillaria thunbergii, Sargassum, Oyster shell, and Pumice, which possess phlegm-resolving and mass-softening actions[19]. Sparganium rhizome and Curcuma rhizome, being able to reverse blood stagnation and improve circulation, promote nodule dispersion[20]. Through liver qi flow regulation, Bupleurum root and Curcuma aromatica help prevent liver qi stagnation from exacerbating phlegm coagulation[21]. Sinapis alba and Pinellia ternata warm the body and resolve cold phlegm[22]. Hedyotis diffusa and Prunella vulgaris are helpful for clearing heat, detoxifying, and reducing swelling[23]. While being able to nourish yin and cool the blood, dried Rehmannia Root also possesses the function of counteracting potential yin damages caused by warm-natured herbs (e.g., Sinapis alba and Pinellia ternata)[24]. These ingredients are complementary in their effects, jointly playing the role of blood activation, turbidity elimination, body resistance enhancement, and pathogen factor removal. Importantly, this study attaches critical importance to standardizing and controlling the quality of TCM compound formulations. As such, the consistency and reliability of the intervention can be ensured, allowing for accurate interpretation of results and future clinical transformation. We further conducted in-depth research on the therapeutic mechanism of JPHZXYD in TN treatment. Astragalus polysaccharide, a key Astragalus membranaceus component, is highly immunomodulatory. Astragalus polysaccharide can modulate immune function across central and peripheral immune organs, including the bone marrow, thymus, lymph nodes, spleen, and mucosal tissues, by enhancing the activity of macrophages, natural killer cells, dendritic cells, T and B lymphocytes, and microglia, as well as by inducing the expression of various cytokines and chemokines[25]. In animal studies, Atractylodes macrocephala polysaccharide has been shown to reduce inflammatory damage and oxidative stress by regulating the Toll-like receptor 4-myeloid differentiation primary response protein 88-nuclear factor κB signaling pathway. Since inflammation and oxidative stress are key mediators in TN pathogenesis, these effects may underlie the therapeutic benefit of Atractylodes macrocephala in TN management[26-28]. Previous studies have also demonstrated that adjunctive treatment of TNs with Prunella vulgaris extract not only improves clinical outcomes and reduces nodule size but also helps prevent adverse reactions. The mechanism of action is thought to involve antiproliferative, antioxidant, and immunomodulatory effects[29,30].
This study demonstrates that JPHZXYD effectively reduces TN size; alleviates symptoms such as chest oppression, pain, and mood disturbances; mitigates anxiety and depression; and improves overall treatment efficacy. Astragalus membranaceus, a key component of JPHZXYD, has been reported to exert anticancer effects in thyroid cancer by reducing oxidative stress[31], which may partially explain the observed therapeutic benefits in TN management[31]. When assessing TN parameters, JPHZXYD was found to statistically reduce nodule counts, average nodule diameters, and microvascular densities, suggesting its potential utility in inhibiting TN progression. TN cases who received JPHZXYD also displayed lower PI and RI values than their counterparts who received the lifestyle intervention. PI and RI are potential predictors of disease progression, as their elevated levels are associated with thyroid carcinoma and adverse outcomes[32]. Furthermore, JPHZXYD was found to enhance thyroid function in TN cases, elevating FT3 and FT4, decreasing TSH, and reducing thyroid autoantibodies (TPOAb and TgAb), dynamics in line with the results reported by Sun et al[33]. Notably, although FT3 and FT4 rose evidently from baseline in the observation group after JPHZXYD treatment, higher than the control group values, their means (FT3: 5.6 pmol/L; FT4: 17.5 pmol/L) remained well within the normal clinical reference ranges of our laboratory (FT3: 3.1 pmol/L to 6.8 pmol/L; FT4: 12 pmol/L to 22 pmol/L). The observed elevation, rather than inducing pathological hyperactivity, is essentially a thyroid function optimization within the normal range. This regulatory effect may improve overall patient health and help establish a stable endocrine environment that inhibits nodule growth. Previous research has shown that the large-head rhizome of Atractylodes macrocephala and its bioactive compounds can ameliorate hypothyroidism by enhancing metabolic and energy processes[34], which may partially explain the mechanism by which JPHZXYD improves thyroid function in patients with TN. Additionally, Xu et al[35] reported a positive association between elevated TPOAb and TgAb levels and increased TN risk among coastal Chinese adults. In this study, JPHZXYD exhibited lower TgAb levels, suggesting the preventive and therapeutic efficacy of the decoction.
This study has several limitations: First, the 28-day intervention period may be insufficient to fully evaluate changes in TN size and the long-term stability of emotional outcomes. Future studies should include extended follow-up; second, the single-center design with a modest sample size (n = 123) limits generalizability, and larger, multicenter randomized controlled trials are warranted to strengthen the findings; and finally, no mechanistic basic research was conducted. Future studies should incorporate in vitro and in vivo experiments to explore the underlying mechanisms of JPHZXYD in TN management.
This study reveals meaningful clinical improvements in TN patients following JPHZXYD plus emotional conditioning therapy. This protocol mitigates symptoms and psychological distress, enhances overall effectiveness, lowers TN number, diameter, and vascularity, as well as PI, RI, TPoAb, and TgAb levels, and improves thyroid function, justifying its routine clinical implementation.
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