1.Mechanism of Shenfu Xiongze Prescription in Regulating Autophagy Level to Intervene in Myocardial Remodeling in Rats via AMPK/mTOR Signaling Pathway
Xueqing WANG ; Wei ZHONG ; Liangliang PAN ; Caihong LI ; Man HAN ; Xiaowei YANG ; Yuanwang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):136-144
ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline (ISO) was established. Rats were divided into the blank group,the model group,the low-,medium-, and high-dose groups of Shenfu Xiongze prescription,and the captopril group, 6 rats in each group. Except for the blank group,the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg-1 ISO for 3 consecutive weeks. At the same time of modeling, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution (8.4,16.8,and 33.6 g·kg-1),and the captopril group was administered captopril solution (25 mg·kg-1). As for the blank group and the model group, the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function,and the heart weight index was detected. Masson staining and hematoxylin-eosin (HE) staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 (IL-6) and B-type natriuretic peptide (BNP) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of type Ⅰ collagen (Collagen Ⅰ),type Ⅲ collagen (Collagen Ⅲ),and microtubule-associated protein 1 light chain 3 (LC3) proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ,Collagen Ⅲ,α-smooth muscle actin (α-SMA),LC3,yeast Atg6 homolog protein (Beclin-1),AMPK,and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction (real-time PCR). The protein expression of Collagen Ⅰ,α-SMA,transforming growth factor-β1 (TGF-β1),LC3,Beclin-1,p62, phosphorylation(p)-AMPK,p-mTOR,AMPK,and mTOR was detected by Western blot. ResultsCompared with the normal group,rats in the model group exhibited significantly decreased values of ejection fraction (EF) and left ventricular fractional shortening (FS) (P<0.01), significantly increased values of left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVIDs) (P<0.01). Additionally, the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue, significantly elevated levels of serum IL-6 and BNP (P<0.01), significantly increased mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,and mTOR (P<0.01),and markedly decreased mRNA and protein levels of LC3,Beclin-1,and AMPK (P<0.05,P<0.01). Compared with the model group, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values (P<0.01) and lowered LVIDd and LVIDs (P<0.05). In these groups, the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP (P<0.01), significantly reduced protein expression of Collagen Ⅰ, α-SMA, TGF-β1, p62, and p-mTOR (P<0.01), significantly decreased mRNA expression of Collagen Ⅰ, Collagen Ⅲ, α-SMA, and mTOR (P<0.01), and significantly increased mRNA and protein levels of LC3, Beclin-1, and AMPK (P<0.05,P<0.01). ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level,enhance cardiac function,and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.
2.Efficacy and safety of sequential or combined therapy with tenofovir alafenamide fumarate in entecavir-treated patients with low-level viremia
Yijing ZHANG ; Lingying HUANG ; Bowu CHEN ; Wanchun ZHU ; Man LI ; Jie SHEN ; Yueqiu GAO
Journal of Clinical Hepatology 2026;42(1):66-73
ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate (TAF) therapy versus the regimen of entecavir (ETV) combined with TAF in chronic hepatitis B (CHB) patients experiencing low-level viremia (LLV) after ETV therapy, as well as their impact on virologic response, liver and renal function, and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled, and according to the treatment regimen, they were divided into TAF group (180 patients receiving sequential TAF therapy) and combined group (37 patients receiving ETV+TAF therapy). The propensity score matching (PSM) method was used to match the patients at a ratio of 1∶1, and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA (HBV DNA) clearance rate, hepatitis B envelope antigen (HBeAg) clearance rate, liver and renal function parameters (liver stiffness measurement [LSM], platelet count [PLT], aspartate aminotransferase [AST], alanine aminotransferase [ALT], and creatinine [Cr]), blood lipid levels (total cholesterol [TC], triglyceride [TG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]), and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the paired t-test was used for comparison within each group; the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment, compared with the TAF group, the combined group had significantly higher HBV DNA clearance rate (86.49% vs 59.46%, χ²=6.852, P=0.009) and HBeAg clearance rate (59.46% vs 35.14%, χ²=4.391, P=0.036). After treatment, compared with the TAF group, the combined group had significantly lower levels of LSM (7.01±1.50 kPa vs 7.90±1.68 kPa, t=2.404, P=0.019), AST (18.02±2.28 U/L vs 21.12±2.85 U/L, t=5.166, P<0.001), and ALT (19.85±3.86 U/L vs 22.00±3.90 U/L, t=2.383, P=0.020) and significantly higher levels of PLT [(218.35±42.60)×109/L vs (192.82±44.13)×109/L, t=2.532, P=0.014] and Cr (70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L, t=2.253, P=0.027). After treatment, there was a slight increase in the level of TC in both the TAF group (5.60±0.89 mmol/L vs 5.18±0.85 mmol/L, t=2.076, P=0.041) and the combined group (5.45±0.80 mmol/L vs 5.02±0.83 mmol/L, t=2.269, P=0.026). There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group (21.62% vs 18.92%, χ²=0.084, P=0.772). ConclusionFor ETV-treated CHB patients experiencing LLV, compared with sequential TAF therapy, the ETV+TAF combined therapy can effectively increase virologic response rate, alleviate liver fibrosis, and improve liver function, whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC, which should be taken seriously in clinical practice.
3.High Expression of INF2 Predicts Poor Prognosis and Promotes Hepatocellular Carcinoma Progression
Hai-Biao WANG ; Man LIN ; Fu-Sang YE ; Jia-Xin SHI ; Hong LI ; Meng YE ; Jie WANG
Progress in Biochemistry and Biophysics 2025;52(1):194-208
ObjectiveINF2 is a member of the formins family. Abnormal expression and regulation of INF2 have been associated with the progression of various tumors, but the expression and role of INF2 in hepatocellular carcinoma (HCC) remain unclear. HCC is a highly lethal malignant tumor. Given the limitations of traditional treatments, this study explored the expression level, clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets. MethodsIn this study, we used public databases to analyze the expression of INF2 in pan-cancer and HCC, as well as the impact of INF2 expression levels on HCC prognosis. Quantitative real time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues. The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples. Subsequently, the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments. Finally, the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments. ResultsINF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival, liver cirrhosis and pathological differentiation of HCC patients. The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC. In vivo and in vitro HCC models, upregulated expression of INF2 triggers the proliferation and migration of the HCC cell, while knockdown of INF2 could counteract this effect. INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression, thus promoting tumor progression. ConclusionINF2 is highly expressed in HCC and is associated with poor prognosis. High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression, and targeting INF2 may be beneficial for HCC patients with high expression of INF2.
4.Prognostic evaluation of liver transplantation for acute-on-chronic liver failure
Man LAI ; Manman XU ; Xin WANG ; Guangming LI ; Yu CHEN
Organ Transplantation 2025;16(3):482-488
Acute-on-chronic liver failure (ACLF) is an acute deterioration of liver function occurring on the basis of chronic liver disease, accompanied by failure of the liver and extrahepatic organs, and is associated with a high short-term mortality rate. Liver transplantation is the only curative treatment for patients with ACLF. However, the shortage of donor livers and limitations of the organ allocation system mean that only a minority of patients can receive transplants. The current organ allocation system based on the model for end-stage liver disease (MELD) score may underestimate the urgency of liver transplantation for ACLF patients. Therefore, it is urgent to develop better assessment tools to determine which ACLF patients are most likely to benefit from liver transplantation. This article reviews the current mainstream definitions of ACLF, the selection of candidates for liver transplantation in ACLF, and the prognostic scoring systems for liver transplantation in ACLF, both domestically and internationally, in order to provide a reference for the prognostic assessment of liver transplantation in ACLF patients.
5.Action research on medical social workers building a doctor-patient community from the interdisciplinary perspective: taking the medical social workers’ service in department of pediatric neurosurgery at Beijing × hospital as an example
Jin DU ; Huiyi YAO ; Zuobing LI ; Man LI
Chinese Medical Ethics 2025;38(5):602-611
With the transformation in modern medical models and the increasingly diversified needs of patients, building a harmonious and mutually trusting doctor-patient community relationship has become the key to improving the quality of medical services, enhancing patients’ sense of access to medical care, and promoting medical effects. Medical social worker is an indispensable member of the medical team, whose interdisciplinary background knowledge and professional skills provide unique advantages for building a harmonious doctor-patient community relationship. However, the current subjects of research on the doctor-patient community are still limited to the medical staff and patients, and there is a lack of relevant research that uses interdisciplinary thinking and tools to explore the path of building a doctor-patient community. Therefore, under the guidance of the spiral research idea of action research method, by sorting out the action paths of medical social workers in carrying out pediatric neurosurgery specialist services in the past five years, three analytical tools from management, namely the strategic decision-making process model, the organization- stakeholder fit model, and the value proposition canvas, were used to solve the problems and dilemmas in the different stages of building a doctor-patient community. On these foundations, practical knowledge was produced, providing valuable experience and methods for medical social workers to build a doctor-patient community.
6.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
7.Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0
Di WU ; Jia-Horng KAO ; Teerha PIRATVISUTH ; Xiaojing WANG ; Patrick T.F. KENNEDY ; Motoyuki OTSUKA ; Sang Hoon AHN ; Yasuhito TANAKA ; Guiqiang WANG ; Zhenghong YUAN ; Wenhui LI ; Young-Suk LIM ; Junqi NIU ; Fengmin LU ; Wenhong ZHANG ; Zhiliang GAO ; Apichat KAEWDECH ; Meifang HAN ; Weiming YAN ; Hong REN ; Peng HU ; Sainan SHU ; Paul Yien KWO ; Fu-sheng WANG ; Man-Fung YUEN ; Qin NING
Clinical and Molecular Hepatology 2025;31(Suppl):S134-S164
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
8.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
9.Update on the treatment navigation for functional cure of chronic hepatitis B: Expert consensus 2.0
Di WU ; Jia-Horng KAO ; Teerha PIRATVISUTH ; Xiaojing WANG ; Patrick T.F. KENNEDY ; Motoyuki OTSUKA ; Sang Hoon AHN ; Yasuhito TANAKA ; Guiqiang WANG ; Zhenghong YUAN ; Wenhui LI ; Young-Suk LIM ; Junqi NIU ; Fengmin LU ; Wenhong ZHANG ; Zhiliang GAO ; Apichat KAEWDECH ; Meifang HAN ; Weiming YAN ; Hong REN ; Peng HU ; Sainan SHU ; Paul Yien KWO ; Fu-sheng WANG ; Man-Fung YUEN ; Qin NING
Clinical and Molecular Hepatology 2025;31(Suppl):S134-S164
As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.
10.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

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