1.Mechanism Study of Yinchenhao Tang Regulating Fas/Caspase-8/Caspase-3 Signaling Pathway to Improve Cholestatic Liver Injury
Zhengwang ZHU ; Linlin WANG ; Jinghan ZHAO ; Linjing SHE ; Yinpei TANG ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):39-46
ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 (Fas)/cysteine protease-8 (Caspase-8)/cysteine protease-3 (Caspase-3) signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury (CLI). MethodsAmong 48 Wistar rats,12 rats were randomly selected as the blank group,and the other rats were administered alpha-naphthalene isothiocyanate (ANIT) by gavage to induce a CLI model. The modeling rats were randomly divided into the model group, the ursodeoxycholic acid group(0.1 g·kg-1) and the Yinchenhao Tang group(9.23 g·kg-1),with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma-glutamyl transpeptidase (γ-GT),total bilirubin (TBil) and total bile acid (TBA) in serum were detected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin (HE) staining. The protein and mRNA expressions of Fas,Caspase-8,Caspase-3,B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with those in the blank group,the levels of ALT,AST,ALP,γ-GT,TBA and TBil in serum of the model group were significantly increased (P<0.01). The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased (P<0.01). The arrangement of hepatocytes was disordered,and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly increased(P<0.05,P<0.01),while the protein and mRNA expressions of Bcl-2 were significantly decreased (P<0.05,P<0.01). Compared with those in the model group,the levels of ALP,γ-GT,TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased(P<0.05,P<0.01). The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased (P<0.05,P<0.01),while the mRNA expression of Bcl-2 was significantly increased (P<0.05,). The levels of ALT,AST,γ-GT,TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased (P<0.01). The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased (P<0.05,P<0.01). The protein expression of Fas and Bax and the mRNA expression of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased (P<0.05,P<0.01),while the protein and mRNA expression of Bcl-2 were significantly increased (P<0.05,P<0.01). Hepatocyte injury,inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI,and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.
2.Mechanism of Yinchenhao Tang in Improving Cholestatic Liver Injury by Inhibiting TLR4/MyD88/NF-κB Signaling Pathway Through FXR
Zhengwang ZHU ; Yang YANG ; Jinghan ZHAO ; Linlin WANG ; Yinpei TANG ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):47-54
ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury (CLI) by inhibiting toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) pathway via regulating farnesol X receptor (FXR). MethodsA total of 40 Wistar male rats were randomly selected, with 10 as a blank group,and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate (ANIT). After modeling,they were randomly divided into the model group, the ursodeoxycholic acid (0.1 g·kg-1) group and the Yinchenhao Tang (9.23 g·kg-1) group,with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),γ-glutamyl transpeptidase (γ-GT),total bile acid (TBA),total bilirubin (TBil) and direct bilirubin (DBil) levels in serum were detected. Tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),and interleukin-6 (IL-6) levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR,TLR4,MyD88,NF-κB,F4/80,TNF-α,IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR,TLR4,MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin (HE) staining. ResultsCompared with those in the blank group,ALT,AST,ALP,γ-GT,TBA,TBil and DBil levels in serum of rats in the model group were significantly increased (P<0.01). The levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were significantly increased (P<0.01),and the mRNA and protein expressions of FXR in liver tissue were decreased (P<0.01). The mRNA and protein expressions of TLR4,MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased (P<0.05,P<0.01). Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group,ALT,ALP,γ-GT,TBA,TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased (P<0.05,P<0.01),and the levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were obviously decreased (P<0.05,P<0.01). The mRNA and protein expressions of TLR4,MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased (P<0.05,P<0.01). ALT,AST,ALP,γ-GT,TBA,TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased (P<0.05,P<0.01),and the levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were obviously decreased (P<0.01). The mRNA and protein expressions of FXR in liver tissue were significantly increased,and the mRNA expressions of TLR4,MyD88,NF-κB,and F4/80, as well as the protein expressions of TLR4 and NF-κB were obviously decreased (P<0.05,P<0.01). The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI,and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.
3.Yinchenhao Tang Regulates Pyroptosis to Intervene in Cholestatic Liver Injury
Linlin WANG ; Zhengwang ZHU ; Jinghan ZHAO ; Ruixue MA ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):55-62
ObjectiveTo explore the mechanism by which Yinchenhao Tang intervenes in α-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury by regulating the Takeda G-protein-coupled receptor 5(TGR5)/NOD-like receptor protein 3(NLRP3)/cysteine aspartate-specific protease-1 (Caspase-1) pyroptosis signaling pathway. MethodsForty male Wistar rats were randomly assigned into blank, model, ursodeoxycholic acid, and Yinchenhao Tang groups. Except the blank group, other groups were treated with ANIT dissolved in olive oil for the modeling of cholestatic liver injury. Ursodeoxycholic acid (0.1 g·kg-1) and Yinchenhao Tang (9.23 g·kg-1) were administered by gavage. The blank group and the model group were administrated with the same amount of pure water, once a day for 3 days. The blood and liver tissue samples were collected, and the serum levels of liver function indicators were measured by an automatic biochemical analyzer. Hematoxylin-eosin staining was employed to observe the pathological changes of the liver. The levels of interleukin (IL)-1β and IL-18 in the liver tissue were determined by ELISA. The mRNA levels of IL-1β, IL-18, TGR5, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and GSDMD in the liver tissue were assessed by Real-time PCR. The protein levels of TGR5, NLRP3, ASC, Caspase-1, and GSDMD in the liver tissue were determined by Western blot. ResultsCompared with the blank group, the model group showed elevated levels of alanine amino-transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), total bile acid (TBA), and total bilirubin (TBil) in the serum (P<0.01), inflammatory cell infiltration, hepatocyte swelling, and bile duct epithelial cell proliferation in the liver, raised levels of IL-1β and IL-18 in the liver tissue (P<0.01), down-regulated mRNA and protein levels of TGR5 (P<0.01), up-regulated mRNA levels of IL-18 (P<0.01), ASC (P<0.01), Caspase-1 (P<0.01), GSDMD (P<0.01), IL-1β (P<0.05), and NLRP3 (P<0.05), and up-regulated protein levels of NLRP3 (P<0.01), ASC (P<0.01), Caspase-1 (P<0.01), and GSDMD (P<0.05). Compared with the model group, the ursodeoxycholic acid group showed declined levels of AST (P<0.01), TBA (P<0.01), TBil (P<0.01), and ALT (P<0.05) in the serum, lowered levels of IL-1β and IL-18 in the liver tissue (P<0.01), down-regulated mRNA levels of NLRP3 (P<0.01), Caspase-1 (P<0.01), GSDMD (P<0.01), IL-1β (P<0.05), IL-18 (P<0.05), and ASC (P<0.05), up-regulated mRNA and protein levels of TGR5 (P<0.05), and down-regulated protein levels of NLRP3, ASC, Caspase-1, and GSDMD (P<0.05). Compared with the model group, the Yinchenhao Tang group showed lowered levels of ALT, AST, ALP, TBA, and TBil in the serum (P<0.01), declined levels of IL-1β and IL-18 in the liver tissue (P<0.01), down-regulated mRNA levels of IL-1β (P<0.01), NLRP3 (P<0.01), ASC (P<0.01), Caspase-1 (P<0.01), GSDMD (P<0.01), and IL-18 (P<0.05), up-regulated mRNA and protein levels of TGR5 (P<0.01), and down-regulated protein levels of Caspase-1 and GSDMD (P<0.05). The liver tissue of the administration groups showed reduced infiltration of inflammatory cells, reduced swelling of hepatocytes, and alleviated proliferation of bile duct epithelial cells. ConclusionYinchenhao Tang can ameliorate ANIT-induced cholestatic liver injury by regulating the hepatocyte pyroptosis mediated by the TGR5/NLRP3/Caspase-1 signaling pathway.
4.Intervention Effect and Regulation Mechanism of Yinchenhao Tang on Cholestatic Liver Injury
Linlin WANG ; Zhengwang ZHU ; Jinghan ZHAO ; Ruixue MA ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):71-80
Cholestatic liver injury refers to the bile production, secretion, and excretion disorder caused by various reasons. It induces liver injury, metabolic disorders, and dysfunction of the hepatobiliary system, which can further develop into liver fibrosis, cirrhosis, liver failure, and even death. At present, the preferred drug for clinical treatment is ursodeoxycholic acid, which, however, induces adverse reactions and is intolerant in some patients. Yinchenhao Tang is a representative prescription of traditional Chinese medicine for the treatment of jaundice due to Yang jaundice. It has the effects of clearing heat, eliminating dampness, and removing jaundice and has shown good therapeutic effect in long-term clinical application. Modern pharmacological studies have found that this prescription has anti-inflammatory, anti-oxidation, bile acid balance-regulating, hepatocyte apoptosis-inhibiting and other liver-protecting effects. This paper reviews the relevant clinical and animal experimental studies on Yinchenhao Tang in the treatment of cholestatic liver injury in recent years. Yinchenhao Tang can intervene in the progression of cholestatic liver injury by regulating bile acid metabolism and excretion, reducing inflammatory response, inhibiting oxidative stress, alleviating endoplasmic reticulum stress, inhibiting hepatocyte apoptosis, and protecting intestinal mucosal barrier. This paper systematically expounds the molecular mechanisms by which Yinchenhao Tang regulates cholestatic liver injury that are confirmed by current research, aiming to provide reference for the clinical application and in-depth study of Yinchenhao Tang.
5.Solitary Progression to Bone: A Rare Manifestation of Adrenocortical Carcinoma
Mohd Fyzal Bahrudin ; Jia Miao Tan ; Chin Voon Tong
Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):31-32
Introduction:
Adrenocortical carcinoma (ACC) is a rare and aggressive
malignancy with a predilection for metastasis to the liver,
lungs, and lymph nodes. Bone involvement is less common
and typically occurs alongside widespread disease.
Isolated skeletal progression without visceral involvement
is unusual and not well characterized.
Case:
A 60-year-old female underwent left adrenalectomy in
2019 for an incidentally detected adrenal mass, which
was reported as a benign adrenal cortical adenoma (Ki67 <3%). In 2022, she presented with persistent low
back pain. Imaging demonstrated fluorodeoxyglucoseavid lesions involving the T12 vertebra and right
ilium, without evidence of local recurrence or visceral
metastases. Histopathological evaluation of a bone biopsy
initially suggested a neuroendocrine neoplasm based
on synaptophysin positivity. Following multiple expert
reviews and integration of clinical, radiological, and
immunohistochemical findings, a consensus diagnosis of
metastatic ACC was established.
She received palliative radiotherapy to symptomatic
skeletal sites and subsequently completed six cycles of
etoposide, doxorubicin, and cisplatin chemotherapy in
2023, achieving disease stabilization. Surveillance imaging
in May 2025 demonstrated progression confined to the
axial and appendicular skeleton, with no involvement of
the adrenal bed or visceral organs. Mitotane therapy was
initiated in December 2025. Ongoing management focuses
on systemic disease control, symptom palliation, and
multidisciplinary supportive care.
Conclusion
This case illustrates an uncommon pattern of ACC
progression characterized by bone-dominant metastases
in the absence of visceral disease. It also highlights the
importance of reconsidering the initial histopathological
diagnosis when clinical behavior is discordant. Vigilance
for atypical metastatic patterns is warranted, even years
after resection of an adrenal lesion initially classified as
benign.
Adrenocortical Carcinoma
6.Tuihuang Mixture improves α‑naphthylisothiocyanate-induced cholestasis in rats by inhibiting NLRP3 inflammasomes via regulating farnesoid X receptor.
Zhengwang ZHU ; Linlin WANG ; Jinghan ZHAO ; Ruixue MA ; Yuchun YU ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Journal of Southern Medical University 2025;45(4):718-724
OBJECTIVES:
To study the therapeutic mechanism of Tuihuang Mixture against cholestasis.
METHODS:
Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining.
RESULTS:
The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models.
CONCLUSIONS
Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals
;
NLR Family, Pyrin Domain-Containing 3 Protein
;
Rats
;
Receptors, Cytoplasmic and Nuclear/metabolism*
;
Cholestasis/drug therapy*
;
Rats, Wistar
;
Inflammasomes/metabolism*
;
1-Naphthylisothiocyanate
;
Drugs, Chinese Herbal/therapeutic use*
;
Male
;
Interleukin-18/metabolism*
;
Caspase 1/metabolism*
;
Interleukin-1beta/metabolism*
;
Liver/metabolism*
7.Senescent Nociceptors: A Novel Therapeutic Target for Chronic Pain Treatment.
Shi-Yu SUN ; Xiu-Hua MIAO ; Guo-Kun ZHOU ; Tong LIU
Neuroscience Bulletin 2025;41(12):2322-2325
8.Prevalence and risk factors of training-related abdominal injuries: A multicenter survey study.
Chuan PANG ; Wen-Quan LIANG ; Gan ZHANG ; Ting-Ting LU ; Yun-He GAO ; Xin MIAO ; Zhi-Da CHEN ; Yi LIU ; Wen-Tong XU ; Hong-Qing XI
Chinese Journal of Traumatology 2025;28(4):301-306
PURPOSE:
This study aims to identify the prevalence and risk factors of military training-related abdominal injuries and help plan and conduct training properly.
METHODS:
This questionnaire survey study was conducted from October 2021 to May 2022 among military personnel from 6 military units and 8 military medical centers and participants' medical records were consulted to identify the training-related abdominal injuries. All the military personnel who ever participated in military training were included. Those who refused to participate in this study or provided an incomplete questionnaire were excluded. The questionnaire collected demographic information, type of abdominal injury, frequency, training subjects, triggers, treatment, and training disturbance. Chi-square test and t-test were used to compare baseline information. Univariate and multivariate regression analyses were used to explore the risk factors associated with military training-related abdominal injuries.
RESULTS:
A total of 3058 participants were involved in this study, among which 1797 (58.8%) had suffered training-related abdominal injuries (the mean age was 24.3 years and the service time was 5.6 years), while 1261 (41.2%) had no training-related abdominal injuries (the mean age was 23.1 years and the service time was 4.3 years). There were 546 injured patients (30.4%) suspended the training and 84 (4.6%) needed to be referred to higher-level hospitals. The most common triggers included inadequate warm-up, fatigue, and intense training. The training subjects with the most abdominal injuries were long-distance running (589, 32.8%). Civil servants had the highest rate of abdominal trauma (17.1%). Age ≥ 25 years, military service ≥ 3 years, poor sleep status, and previous abdominal history were independent risk factors for training-related abdominal injury.
CONCLUSION
More than half of the military personnel have suffered military training-related abdominal injuries. Inadequate warm-up, fatigue, and high training intensity are the most common inducing factors. Scientific and proper training should be conducted according to the factors causing abdominal injuries.
Humans
;
Military Personnel
;
Risk Factors
;
Prevalence
;
Male
;
Abdominal Injuries/etiology*
;
Female
;
Adult
;
Surveys and Questionnaires
;
Young Adult
9.Expert Consensus on Perioperative Nursing Care for Follicular Unit Extraction(2025)
Chunhua ZHANG ; Weiwei BIAN ; Congmin WANG ; Lin SHEN ; Yong MIAO ; Na LIU ; Shan JIA ; Junhong AN ; Hongxia WANG ; Dongmei ZHANG
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1606-1613
To promote the standardization and normalization of perioperative care for follicular unit extraction(FUE) hair transplantation, ensure treatment efficacy, and align with advancements in the specialty, the Nursing Branch of the Chinese Association of Plastic and Aesthetics organized a panel of domestic experts. By integrating evidence-based medicine with clinical practice experience, and following thorough discussions, these experts developed the Clinical Practice
10.The regulatory role and mechanism of microRNA in cholestasis
Linlin WANG ; Zhengwang ZHU ; Jinghan ZHAO ; Ruixue MA ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Journal of Clinical Hepatology 2025;41(10):2187-2194
As a type of endogenous small non-coding RNA, microRNA (miRNA) can regulate gene expression and thereby intervene against the development and progression of cardiovascular diseases, neurodegenerative diseases, metabolic diseases, and autoimmune diseases. The pathogenesis of cholestasis is complex and is mainly associated with the metabolism and transport of bile acids, oxidative stress, inflammatory response, and intestinal flora. Currently, ursodeoxycholic acid is the preferred drug for the clinical treatment of cholestasis, but it may cause adverse reactions and exhibit poor efficacy in some patients. Studies have shown that miRNA can intervene in the disease process of cholestasis through multiple mechanisms such as regulating bile acid metabolism and transport, alleviating oxidative stress, inhibiting inflammatory response, improving cholangiocyte proliferation, and regulating intestinal flora. It can be used as a new biomarker and action target for cholestasis, with high research potential and value. Therefore, this article summarizes the role and mechanisms of miRNA in regulating cholestasis in recent years, in order to provide a reference for further research on the prevention and treatment of cholestasis by targeting miRNA.


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