A retrospective cohort study of tamoxifen versus surgical treatment for ER-positive gynecomastia.

BACKGROUND: Gynecomastia is a common condition in clinical practice. The present study aimed to review the clinical data of ER-positive gynecomastia patients treated by tamoxifen (TAM) versus surgery and discussed the clinical effects of the two treatment strategies. METHOD: We retrospectively collected the clinical indicators of patients with unilateral or bilateral gynecomastia who received treatment at our hospital between April 2018 and December 2021. Depending on the treatment received, the patients were divided into TAM and surgery groups. RESULT: A total of 170 patients were recruited, including 91 patients in TAM group and 79 patients in surgery group. The age of the patients differed significantly between the TAM and surgery groups (P < 0.01). The estrogen level was closer in patients with stable and progressive disease, but significantly different in patients of glandular shrinkage in TAM group (P < 0.01). The proportion of patients achieving stable disease was higher among those with clinical grade 1-2. Among patients classified as clinical grade 3, the proportion of patients achieving glandular shrinkage of the breast was higher after TAM treatment (P < 0.05). The age and length of hospital stay were significantly different in patients undergoing open surgery than minimally invasive rotary cutting surgery and mammoscopic-assisted glandular resection (P < 0.01). Patients had significantly different complications including mild postoperative pain, hematoma, nipple necrosis, nipple paresthesias and effusions among the surgery subgroups (all P < 0.05). The estrogen level and the type of surgery were significantly different between the surgical recurrence and non-recurrence subgroups (P < 0.05). The difference in the thickness of glandular tissues upon the color Doppler ultrasound also reached a statistical significance between the two groups (P = 0.050). An elevated estrogen level was a factor leading to TAM failure. Among surgical patients, the thickness of glandular tissues, estrogen level, and type of surgery performed were risk factors for postoperative recurrence (all P < 0.05). CONCLUSION: Both treatment strategies can effectively treat gynecomastia, but different treatment methods can benefit different patients. TAM treatment is more beneficial than surgery for patients who cannot tolerate surgery, have a low estrogen level, and are clinical grade 1-2. Surgery treatment is better than TAM for patients of clinical grade 3. Different surgery options may lead to different complications. Patients with a greater glandular tissue thickness and a higher estrogen level were shown to have a higher risk of recurrence.

A comparative study of the efficacy of tamoxifen and Chinese patented medicine (Pingxiao capsules) in gynecomastia: A retrospective cohort study.

To compare the clinical efficacy of tamoxifen and Chinese patented medicine (Pingxiao capsules) in patients with gynecomastia and discuss the safety of the two treatments. We retrospectively analysed the clinical data of 388 male patients with gynecomastia who were treated in the Outpatient Clinic of our hospital between January 2010 and December 2020. There were 103 patients in the tamoxifen (TAM) group and 103 patients in the Chinese patented medicine group. There were 182 patients in the observation group (non-medication group; age range, 11-75 years; average age, 33.1 years). The natural outcomes were compared between the observation and two medication groups under the same conditions. Disease progression was compared between the observation and two medication groups over the same treatment duration to confirm the efficacy of the medication treatments. Patients with clinical grade 2 gynecomastia accounted for the highest proportion of patients in the TAM group. The percentage of patients with clinical grade 2 gynecomastia was comparable in the Chinese patented medicine and observation groups. The percentage of patients with clinical grades 1 and 3 gynecomastia was the lowest in the TAM group and comparable among the three groups (p = 0.014). The TAM group had the largest number of patients achieving breast shrinkage, and therefore had the best efficacy (p = 0.000). Among the three groups, the surgery rate was the highest in the observation group (p = 0.000). Patients with the greatest glandular tissue thickness achieved better outcomes after medication treatment (p = 0.000). Patients with a higher clinical grade also had a higher surgery rate (p = 0.000). Some patients from the TAM and Chinese patented medicine groups had side effects. TAM results in better outcomes than Chinese patented medicine in gynecomastia patients. The surgery rate is the highest in the observation group. In addition, among some patients with a greater glandular tissue thickness, the higher the clinical grade is, the higher the surgery rate is. Both TAM and Chinese patented medicine cause some side effects and should be used with caution along with continuous follow-up evaluation of patients receiving either treatment.

Gastric Mammalian Target of Rapamycin Signaling Contributes to Inhibition of Ghrelin Expression Induced by Roux-En-Y Gastric Bypass.

BACKGROUND/AIMS: Roux-en-Y Gastric Bypass, RYGB, is the most effective strategy to control body weight in morbid obesity. RYGB leads to rapid improvement of glycemic status and weight loss, which are largely attributed to the alteration of gastrointestinal hormones including ghrelin. The current study examined potential mechanisms of altered ghrelin synthesis after RYGB. METHODS: Gastric mammalian target of rapamycin (mTOR) signaling, ghrelin synthesis and secretion were determined in lean or obese male mice with or without RYGB operation, as well as in obese patients pre- and post-RYGB surgery. Ghrelin expression and mTOR signaling were investigated by western blotting and immunohistochemistry. Ghrelin mRNA levels were detected by real-time PCR. Plasma ghrelin was measured by enzyme immunoassay. RESULTS: mTOR activity in the gastric fundus was significantly lower than in the forestomachs. Both of them were decreased after 24h fasting. A significant negative correlation was found between gastric levels of phospho-S6 (phospho-S6 ribosomal protein) and proghrelin during changes of energy status. mTOR activity was activated, whereas ghrelin expression was inhibited by Roux-en-Y Gastric Bypass in both rodents and human beings. Increment of ghrelin synthesis and decline of mTOR signaling induced by rapamycin were significantly reversed by RYGB in both lean and obese mice. Administration of Ad-S6K1 (adenovirus-mediated p70 ribosomal protein subunit 6 kinase 1) from tail vein suppressed the expression of ghrelin in RYGB-operated mice relative to control animals. CONCLUSION: mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of ghrelin after Roux-en-Y Gastric Bypass.

Endoscopic thyroidectomy via areola approach: summary of 1,250 cases in a single institution.

BACKGROUND: The aim of this study was to evaluate the effect and cosmetic results of endoscopic thyroidectomy (ETE) via the areola approach for patients with thyroid diseases. METHODS: A total of 1,250 patients with thyroid diseases underwent ETE via the areola approach between April 2005 and January 2011. Of these, 898 were benign goiters, 260 were Graves' disease, 28 were secondary hyperthyroidism, and 64 were papillary carcinomas. RESULTS: The surgery was successfully completed in 1,249 cases, and 1 case was converted to open surgery. The mean operation time, estimated blood loss, and hospital stay after surgery for patients with a goiter, hyperthyroidism, and papillary carcinoma were 94.4 min, 15.2 ml, 5.0 days, 97.9 min, 16.1 ml, 5.5 days, and 134.3 min, 18.6 ml, 6.4 days, respectively. Complications included 4 cases of postoperative bleeding, 1 case of transection of the recurrent laryngeal nerve (RLN) on one side, 7 cases of temporary RLN injury, 34 cases of transient hypocalcemia, 5 cases of skin bruising on the chest wall, and 1 case of subcutaneous infection in the neck. At 4.6-year (2.5-8 years) follow-up of 1,185 (94.8 %) patients, 3 patients with Graves' disease had recurrence of hyperthyroidism, and 4 patients with nodular goiter had recurrence of small nodules. Four patients had discomfort on swallowing, 4 patients had an abnormal sensation of skin traction on the neck and the chest, and 1 patient with scar diathesis had mild scar hyperplasia. A total of 876 patients were satisfied, 4 equivocal, and 0 unsatisfied with the cosmetic results. CONCLUSION: ETE via the areola approach for patients with benign goiters, Graves' disease, secondary hyperthyroidism, and papillary carcinomas without metastasis to lateral cervical lymph nodes is an effective and safe procedure with excellent cosmetic results.

Long-term effects of laparoscopic sleeve gastrectomy versus roux-en-Y gastric bypass for the treatment of Chinese type 2 diabetes mellitus patients with body mass index 28-35 kg/m(2).

BACKGROUND: To compare long term effects of two bariatric procedures for Chinese type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) of 28-35 kg/m(2). METHODS: Sixty four T2DM patients with Glycated hemoglobin A1c (HbA1c) ≧ 7.0 % were randomly assigned to receive laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedure. Weight, percentage of excess weight loss (%EWL), BMI, waist circumference, HbA1c, fasting blood glucose (FBG), and C-peptide were measured. Serum lipid levels were also measured during three-year postoperative follow-up visits. RESULTS: Fifty five patients completed the 36-month follow-up. Both groups had similar baseline anthropometric and biochemical measures. At the end point, 22 patients (78.6 %) in SG group and 23 patients (85.2 %) in RYGB group achieved complete remission of diabetes mellitus with HbA1c < 6.0 % (P = 0.525) and without taking diabetic medications, and 25 patients in each group (89.3 % vs. 92.6 %) gained successful treatment of diabetes with HbA1c≦6.5 % (P = 0.100). Change in HbA1c, FBG and C peptide were comparable in the two groups. The RYGB group had significantly greater weight loss than the SG group [percentage of total weight loss (%TWL) of 31.0 % vs. 27.1 % (P = 0.049), %EWL of 92.3 % vs. 81.9 % (P = 0.003), and change in BMI of 11.0 vs. 9.1 kg/m(2)(P = 0.017), respectively]. Serum lipids in each group were also greatly improved. CONCLUSION: In this three-year study, SG had similar positive effects on diabetes and dyslipidemia compared to RYGB in Chinese T2DM patients with BMI of 28-35 kg/m(2). Longer term follow-ups and larger sample studies are needed to confirm these outcomes, however.

Gastric mechanosensitive channel Piezo1 regulates ghrelin production and food intake.

Ghrelin, produced mainly by gastric X/A-like cells, triggers a hunger signal to the central nervous system to stimulate appetite. It remains unclear whether X/A-like cells sense gastric distention and thus regulate ghrelin production. Here we show that PIEZO1 expression in X/A-like cells decreases in patients with obesity when compared to controls, whereas it increases after sleeve gastrectomy. Male and female mice with specific loss of Piezo1 in X/A-like cells exhibit hyperghrelinaemia and hyperphagia and are more susceptible to overweight. These phenotypes are associated with impairment of the gastric CaMKKII/CaMKIV-mTOR signalling pathway. Activation of PIEZO1 by Yoda1 or gastric bead implantation inhibits ghrelin production, decreases energy intake and induces weight loss in mice. Inhibition of ghrelin production by Piezo1 through the CaMKKII/CaMKIV-mTOR pathway can be recapitulated in a ghrelin-producing cell line mHypoE-42. Our study reveals a mechanical regulation of ghrelin production and appetite by PIEZO1 of X/A-like cells, which suggests a promising target for anti-obesity therapy.

Interleukin-27 decreases ghrelin production through signal transducer and activator of transcription 3-mechanistic target of rapamycin signaling.

Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Here we investigated that signal transducer and activator of transcription 3 (STAT3)-mechanistic target of rapamycin (mTOR) signaling mediates the suppression of ghrelin induced by IL-27. Co-localization of interleukin 27 receptor subunit alpha (WSX-1) and ghrelin was observed in mouse and human gastric mucosa. Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57BL/6J mice and high-fat diet-induced-obese mice. IL-27 inhibited the production of ghrelin in mHypoE-N42 cells. Inhibition of mTOR activity induced by mTOR siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells. Stat 3 siRNA also abolished the inhibitory effect of IL-27 on ghrelin. IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells. In conclusion, IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.

Stat3-mTOR signaling mediates the stimulation of GLP-1 production induced by IL-27.

GLP-1 is a potent glucose-dependent insulinotropic hormone derived from intestinal L cells. Inflammatory Interleukin-27 (IL-27), a pleiotropic two-chain cytokine, is composed of EBI3 and IL-27 p28 subunits. IL-27 has a protective effect on pancreatic ß-cell function. The relationship between IL-27 and GLP-1 is still unexplored. Here we showed interleukin-27-stimulated GLP-1 production via the Stat3-mTOR-dependent mechanism. Interleukin 27 receptor subunit alpha (IL-27 Rα) was detected in ileum and STC-1 cells. Co-localization of EBI3 and GLP-1 was observed not only in mouse ileums but also in human ileums and colons. Third-ventricular infusion of IL-27 increased ileal and plasma GLP-1 in both lean C57BL/6J mice and diet-induced obese and diabetic mice. These changes were associated with a significant increase in Stat3-mTOR activity. Treatment of STC-1 cells with IL-27 contributed to the increments of Stat3-mTOR signaling and GLP-1. Interference of mTOR activity by mTOR siRNA or rapamycin abolished the stimulation of GLP-1 production induced by IL-27 in STC-1 cells. Stat3 siRNA also blocked the stimulus effect of IL-27 on GLP-1. IL-27 increased the interaction of mTOR and Stat3 in STC-1 cells. Our results identify Stat3-mTOR as a critical signaling pathway for the stimulation of GLP-1 induced by IL-27.

Hepatic mTOR-AKT2-Insig2 signaling pathway contributes to the improvement of hepatic steatosis after Roux-en-Y Gastric Bypass in mice.

Roux-en-Y Gastric Bypass (RYGB) remains one of the most effective options in treatment of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are not clear yet. Here, we evaluated the relationship among hepatic mechanistic target of rapamycin (mTOR)-AKT2-insulin-induced gene 2 (Insig2) signaling, lipogenic transcription factors and lipid synthesis enzymes in obese mice with or without RYGB operation. Hepatic mTOR activity and Insig2a were stimulated, while AKT2, sterol response element-binding protein 1c (SREBP1c), peroxisome proliferator-activated receptor γ (PPARγ), lipogenic genes such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were decreased by Roux-en-Y Gastric Bypass in both DMSO and rapamycin treated diet-induced obese (DIO) mice. Increment of hepatic lipogenesis and decline of mTOR signaling induced by rapamycin were significantly reversed by RYGB in DIO mice. RYGB significantly improved high-fat diet- and rapamycin- induced hepatic steatosis by suppression of de novo lipogenesis. Administration of adenovirus-mediated p70 ribosomal protein subunit 6 kinase 1 (Ad-S6K1) from tail vein improved hepatic steatosis. Infusion of Ad-S6K1 suppressed AKT2, SREBP1c, PPARγ, and lipogenesis-related genes while stimulating Insig2a in DIO mice. Ad-S6K1 decreased oleic acid-induced lipid deposition in primary mouse hepatocytes. Our results suggest that mTOR-AKT2-Insig2 signaling pathway contributes to the improvement effect of RYGB on hepatic steatosis induced by high-fat diet.

Takeda G Protein-Coupled Receptor 5-Mechanistic Target of Rapamycin Complex 1 Signaling Contributes to the Increment of Glucagon-Like Peptide-1 Production after Roux-en-Y Gastric Bypass.

BACKGROUND: The mechanism by which Roux-en-Y Gastric Bypass (RYGB) increases the secretion of glucagon-like peptide-1 (GLP-1) remains incompletely defined. Here we investigated whether TGR5-mTORC1 signaling mediates the RYGB-induced alteration in GLP-1 production in mice and human beings. METHODS: Circulating bile acids, TGR5-mTORC1 signaling, GLP-1 synthesis and secretion were determined in lean or obese male C57BL/6 mice with or without RYGB operation, as well as in normal glycemic subjects, obese patients with type 2 diabetes before and after RYGB. RESULTS: Positive relationships were observed among circulating bile acids, ileal mechanistic target of rapamycin complex 1 (mTORC1) signaling and GLP-1 during changes in energy status in the present study. RYGB increased circulating bile acids, ileal Takeda G protein-coupled receptor 5 (TGR5) and mTORC1 signaling activity, as well as GLP-1 production in both mice and human subjects. Inhibition of ileal mTORC1 signaling by rapamycin significantly attenuated the stimulation of bile acid secretion, TGR5 expression and GLP-1 synthesis induced by RYGB in lean and diet-induced obese mice. GLP-1 production and ileal TGR5-mTORC1 signaling were positively correlated with plasma deoxycholic acid (DCA) in mice. Treatment of STC-1 cells with DCA stimulated the production of GLP-1. This effect was associated with a significant enhancement of TGR5-mTORC1 signaling. siRNA knockdown of mTORC1 or TGR5 abolished the enhancement of GLP-1 synthesis induced by DCA. DCA increased interaction between mTOR-regulatory-associated protein of mechanistic target of rapamycin (Raptor) and TGR5 in STC-1 cells. INTERPRETATION: Deoxycholic acid-TGR5-mTORC1 signaling contributes to the up-regulation of GLP-1 production after RYGB.

AMPK-dependent regulation of GLP1 expression in L-like cells.

This study examined whether AMPK, an evolutionarily conserved sensor of cellular energy status, determines the production of glucagon-like peptide-1 (GLP1). A negative relation existed between phosphorylation of AMPKα and the expression and secretion of GLP1 during changes in energy status in STC-1 cells, an L-like cell line. High concentration of glucose (25 mmol/L) decreased AMPKα phosphorylation, whereas it stimulated the expression and secretion of GLP1 relative to 5.6 mmol/L glucose. Serum starvation upregulated AMPKα phosphorylation, whereas it reduced GLP1 production significantly. Stimulation of AMPK phosphorylation by AICAR and overexpression of wild-type AMPKα1, constitutively active AMPKα1 plasmids, or AMPKα1 lentivirus particles suppressed proglucagon mRNA and protein contents in STC-1 cells. Inactivation of AMPK by Compound C, AMPKα1 siRNA or kinase-inactive AMPKα1 mutant increased the expression and secretion of GLP1. Our results suggest that AMPKα1 may link energy supply with the production of GLP1 in L-like cells.

Complete Endoscopic Thyroidectomy via Oral Vestibular Approach Versus Areola Approach for Treatment of Thyroid Diseases.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES(®); American Society for Gastrointestinal Endoscopy [Oak Brook, IL] and Society of American Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]) is gaining interest because it allows operations without skin incisions. The aim of this study was to evaluate the feasibility, safety, and cosmetic results of endoscopic thyroidectomy via the oral vestibular approach (ETOVA) compared with endoscopic thyroidectomy via the areola approach (ETAA) in patients with thyroid diseases. MATERIALS AND METHODS: Eighty-two patients with thyroid diseases were randomized to receive either ETOVA (n=41) or ETAA (n=41). Perioperative and follow-up data were assessed. RESULTS: The surgery was completed in all cases, and all patients were followed up for at least 1 year. There were no differences between the two groups in operation time, blood loss, or postoperative hospital stay. Respective pain scores were 1.7 versus 2.1 and 0.6 versus 0.8 on Days 1 and 3, respectively, postoperatively. The white blood cell counts and C-reactive protein levels were not significantly different between the two groups. Complications were the same in both groups. Oral incision scars were invisible in the ETOVA group. Rates of skin traction sensation on the surgical field were lower in the ETOVA group than in the ETAA group at 3 and 6 months postoperatively (53.7% versus 80.5% and 24.4% versus 46.3%, respectively). The respective satisfaction score was 9.61 versus 9.22 (P=.021). No recurrent cases were observed in the study. CONCLUSIONS: Both the ETOVA and the ETAA procedures are feasible for thyroid diseases. The ETOVA eliminated skin incision scars and gained better cosmetic results in the short-term follow-ups, and the trauma was the same between the two approaches. However, more cases and longer-term follow-ups are needed for confirmation.

Thyroidectomy: a novel endoscopic oral vestibular approach.

BACKGROUND: To date, no report has discussed endoscopic thyroidectomy using the oral vestibular approach (ETOVA). The objective of this study was to evaluate the feasibility, safety, efficacy, and cosmetic results of endoscopic thyroidectomy involving this surgical approach. METHODS: Twenty-four patients with benign thyroid nodules were randomized into the ETOVA (n = 12) and the endoscopic thyroidectomy by areola approach (ETAA) groups (n = 12). Therapeutic effects were assessed at follow-up by physical examination. All patients were followed to evaluate thyroid function and scar formation from endoscopic treatment. RESULTS: Complete resection of all the lesions was performed endoscopically, and no conversion to open surgery was needed. There was no difference between the 2 groups with respect to surgical time (60.4 vs 59.6 min), blood loss (10.8 vs 13.8 mL), postoperative hospital stay (4.9 vs 4.6 d), or cost of surgery (17.6 vs 17.4 thousand yuan). Patients who underwent the areola approach had 3 scars, 10 × 2 mm, 5 × 1 mm, and 5 × 1 mm in size, all of which were visible at the 6-month follow-up. Patients in the ETOVA group did not have any scars. Follow-up showed a significant difference (P = .019) in the satisfaction score between the ETOVA (2.33 ± 0.65) and the ETAA group (1.58 ± 0.79). Imaging showed that all patients had complete resection and no residual disease. Severe complications such as subcutaneous accumulation of blood and fluid, superior or recurrent laryngeal nerve injury, and parathyroid dysfunction were not observed. CONCLUSION: ETOVA was found to be safe and feasible and did not leave any scars; however, large-scale, randomized clinical trials are necessary for confirmation.

[Precise laparoscopic Roux-en-Y gastric bypass in the treatment of 140 patients with obesity and metabolic diseases].

OBJECTIVE: To investigate the efficacy and safety of precise laparoscopic Roux-en-Y gastric bypass(LRYGB) in the treatment of obesity and metabolic diseases. METHODS: Clinical and follow-up data of obese patients underwent precise LRYGB in our department between June 2011 and April 2013 were analyzed retrospectively. RESULTS: A total of 140 obese patients were included in this study. All the precise LRYGB procedures were successfully performed with no conversion to open surgery or perioperative death. Average operation time was (138.0±21.3) min, postoperative hospital stay was (5.2±1.2) d. No severe complications was observed. The percentages of excess weight loss in 1, 3, 6, and 12 month after operation were (26.4±8.6)%, (53.3±6.7)%, (75.3±7.9)%, (78.5±8.5)%, respectively. The improvement rates of fatty liver, hyperlipidemia, hypertension and type 2 diabetes mellitus were 84.6%(33/39), 92.3%(12/13), 77.3%(17/22) and 82.4%(14/17). CONCLUSIONS: Precise LRYGB is a modified and optimized traditional surgical technique which does not significantly increase the operative time. It is safe and feasible. The postoperative weight loss effect is significant and it can effectively improve the related co-morbidities.

[Standardize and pragmatism- the key to promote the healthy development of obesity and metabolic surgery in China].

After more than half a century of development, obesity and metabolic surgery in western countries has become a complete surgical specialties, but the introduction of obesity and metabolic surgery was only 10 years old in China. The surgical treatment of obesity and related metabolic diseases, especially obesity of type 2 diabetes has been recognized and acknowledgd by the majority of surgical colleagues and patients as a new direction of development. The current trend of obesity and metabolic surgery is favorable, but there are many problems in the development of obesity and metabolic surgery in China, for example, the surgery nomenclature is not standardized, surgical indications are loosened, the surgical procedure is modified arbitrarily, the evaluation criteria is confusing, the postoperative follow-up protocol is not unified, etc. These problems require the majority of surgical colleagues to work together to make the standards scientifically a nd objectively in accordance with the actual situatioin of our country, so as to promote the healthy development of obesity and metabolic surgery in China.

Thinking path and method for establishing the disease/Chinese medicine syndrome conjugated pattern of a mammary hyperplasia animal model.

Mammary hyperplasia (MHP) is the most commonly encountered mammary disease in women at the child-bearing stage. Especially, atypical hyperplasia which belongs to the precancerous category, is the disease for class I prevention of breast cancer. Therefore, advancing the clinical efficacy of MHP treatment is of critical importance. Chinese medicine (CM) and drugs show a peculiar effect in this field; the clinical or experimental researches concerning MHP treatment by CM compounds or patent drugs have been increasing gradually in recent years, but the thinking paths and methods for establishing the MHP animal model are divergent. Particularly, the disease/CM syndrome conjugated model (D/S model) has rarely been studied. For this reason, the pathogenetic mechanism, the establishment of an animal disease model, as well as the thinking paths and methods for establishing the D/S model of MHP are discussed and summarized preliminarily in this paper by the authors. This could provide a new way of thinking and method for creating the MHP model in modern medicine.