1.Molecular Mechanism of Liuwei Dihuangwan Regulating GPNMB Expression and Enhancing Autophagy in Prevention and Treatment of Alzheimer's Disease
Yuxi LIU ; Zhongkang ZHU ; Songnan WANG ; Jiali LIU ; Ye YIN ; Jiarui MIAO ; Shunuo HE ; Danyu ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):1-10
ObjectiveThis study aims to investigate the effect of Liuwei Dihuangwan on the autophagy function in the hippocampus of senescence-accelerated mouse prone 8 (SAMP8) by regulating the expression of glycoprotein non-metastatic melanoma protein B (GPNMB). Furthermore, it is designed to explore the mechanism of the method of tonifying the kidneys and replenishing essence in the treatment of Alzheimer's disease (AD). MethodsIn experiment 1, 24 5-month-old SAMP8 mice were randomly and equally divided into the model group, and the low-, middle- and high-dose(0.59,1.18,2.36 g·kg-1) Liuwei Dihuangwan groups. At the same time, six 5-month-old senescence accelerated mouse resistant 1 (SAMR1) mice were used as the control group. The learning and memory ability was evaluated through novel object recognition experiment. Serum cortisol (Cort), adrenocorticotropic hormone (ACTH) and urine 17-hydroxycorticosteroid (17-OHCS) levels were detected by enzyme-linked immunosorbent assay (ELISA). The ultrastructure of hippocampal neurons was observed by transmission electron microscope (TEM), and the expression levels of hippocampal GPNMB, a disintegrin and metalloproteinase 10 (ADAM10) and autophagy-related proteins were detected by Western blot. In experiment 2, 18 SAMP8 mice were randomly and equally divided into the model group, vector control group (Vector), and GPNMB overexpression group (GPNMBOE). Lentiviral vectors were stereotactically injected into the brain (2 μL per side in the GPNMBOE group). Western blot was used to detect the expression of the above target proteins in the hippocampus; In Experiment 3, 24 SAMP8 mice were randomly and equally divided into the model group, Liuwei Dihuangwan group, Liuwei Dihuangwan+negative control (NC) group, and Liuwei Dihuangwan+GPNMB silencing group (shGPNMB). Before drug treatment, the Liuwei Dihuangwan+NC group and the Liuwei Dihuangwan+shGPNMB group were injected with negative control and GPNMB silencing lentivirus, respectively. Western blot was used to detect the expression of the above target proteins in the hippocampus. ResultsThe novel object discrimination index of mice in the model group was significantly lower than that of mice in the control group (P<0.01). The novel object discrimination index of mice in the medium- and high-dose Liuwei Dihuangwan groups was significantly higher than that of mice in the model group (P<0.01). Aggregated autolysosomes were observed in the normal hippocampus tissue by TEM. In the model group, mitochondria were dominant, and no typical characteristic autophagosomes were observed. In the low- and medium-dose Liuwei Dihuangwan groups, a small number of autolysosomes and autophagosomes with double-membrane structures were observed. In the high-dose Liuwei Dihuangwan group, the number of autophagosomes and autolysosomes was greater than that in the low- and medium-dose groups. The results of ELISA and Western blot showed that compared with the control group, the levels of serum Cort, ACTH, and urine 17-OHCS in the model group were substantially increased, while the expression of hippocampal ADAM10, Beclin1, and microtubule associated-protein light chain 3-Ⅱ/Ⅰ (LC3 Ⅱ/Ⅰ) was significantly decreased. The expression of GPNMB and ubiquitin binding protein p62 was significantly increased (P<0.05, P<0.01). Compared with the model group, the serum Cort and ACTH levels in the low-, medium-, and high-dose Liuwei Dihuangwan groups were significantly reduced, while only the urine 17-OHCS level in the high-dose group was significantly reduced. The hippocampal GPNMB, ADAM10, Beclin1, and LC3 Ⅱ/Ⅰ expression levels in the medium-, and high-dose groups of Liuwei Dihuangwan were significantly increased compared to the model group, whereas the expression of p62 was significantly reduced (P<0.01). The above indicators showed a progressive trend among the three groups. Compared with the model group, the GPNMBOE group showed a significant increase in GPNMB, ADAM10, Beclin1, LC3 Ⅱ/Ⅰ expression, and a significant decrease in p62 expression (P<0.01). Compared with the model group, the expression of GPNMB, ADAM10, Beclin1, and LC3 Ⅱ/Ⅰ in the hippocampus of the Liuwei Dihuangwan group significantly increased, while the expression of p62 significantly decreased (P<0.01). Compared with the Liuwei Dihuangwan group, the Liuwei Dihuangwan+shGPNMB group showed a significant decrease in GPNMB, ADAM10, Beclin1, LC3 Ⅱ/Ⅰ, and a significant increase in p62 expression (P<0.01). ConclusionLiuwei Dihuangwan can enhance hippocampal autophagy function and improve AD by upregulating GPNMB expression.
2.Performance validation of a novel multiplex detection reagent for screening transfusion-associated infectious diseases
Miao LIU ; Qian ZHAO ; Na YAO ; Jing LI ; Jiahui ZHANG ; Ning YE ; Yuena XIE
Chinese Journal of Blood Transfusion 2026;39(5):650-655
Objective: To validate the performance of the Procleix UltrioPlex E assay (Grifols, Spain) on the Procleix Panther automated nucleic acid detection platform, which employs the TMA method to simultaneously detect HIV-1/HIV-2/HCV/HBV/HEV viruses, and to evaluate its value for screening transfusion-associated infectious diseases. Methods: In accordance with the requirements of ISO15189"Application of the Guidelines for the Accreditation of Quality and Capabilities of Medical Laboratories in the Field of Molecular Diagnostics (CNAS-CL02-A009: 2018)", "Guidelines for Performance Validation of Molecular Diagnostic Testing Procedures (CNAS-GL039: 2019)", and the "Technical Operating Procedures for Blood Banks (2019 Edition)", this study validated the reagent's performance in terms of analytical sensitivity validation, performance consistency validation, interference resistance, and cross-contamination resistance. Results: Probit analysis revealed that the 95% detection limits (95% confidence interval) for HBV, HCV, HIV, and HEV were 2.0 IU/mL, 1.5 IU/mL, 18.0 IU/mL and 3.7 IU/mL, respectively, which were consistent with the minimum detection limits stated in the kit's package insert and were comparable to the Procleix Ultrio Elite kit. Both kits were used to test the performance validation serum plate simultaneously, yielding results consistent with the serum plate (Kappa=1), indicating stable performance. Detection of medium-and low-concentration lipemia and weakly positive hemolysis samples demonstrated good interference resistance. Cross-contamination performance validation showed that the kit exhibited excellent cross-contamination resistance. Conclusion: The Procleix UltrioPlex E nucleic acid detection kit enables combined detection of HIV-1, HIV-2, HCV, HBV, and HEV, allowing single-test screening for multiple viruses in donor blood. The kit's analytical performance is stable and meets basic laboratory requirements, making it suitable for screening transfusion-associated infectious diseases in blood banks.
3.Guidelines for the management of therapeutic drug monitoring
Zhengxiang LI ; Liyan MIAO ; Rong DUAN ; Xiaocong ZUO ; Xianglin ZHANG ; Zhuo WANG ; Miao YAN ; Lingli ZHANG ; Rongsheng ZHAO ; Suodi ZHAI ; Guobiao GAO ; Jinhui TIAN
China Pharmacy 2026;37(11):1381-1392
OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring (TDM), clarify the clinical value of TDM implementation, improve the scientific validity and reliability of monitoring results, and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization, and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system; evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center, and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules, including TDM application indications, technical procedures, result interpretation and clinical application, and quality control, involving 18 primary research questions, 34 secondary research questions, and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process, provide scientific and operable standardized tools, help improve the standardization level of TDM work, promote the translation of monitoring results into clinical decision-making, and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.
4.A Nomogram for Predicting Metachronous Gastric Cancer After Endoscopic Submucosal Dissection of Early Gastric Cancer Following Successful Helicobacter pylori Eradication
Shangtao MAO ; Miao LIU ; Tao ZHAO ; Qiong YAN ; Ying XIANG ; Hai WU ; Wenjun LI ; Hongji TAO ; Duanming ZHUANG ; Lei WANG ; Guifang XU
Journal of Gastric Cancer 2026;26(2):279-294
Purpose:
Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori.
Materials and Methods:
A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection.
Results:
A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively.
Conclusions
Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.
5.Whole-genome sequencing analysis of co-existing bacteria in platelet products: genomic features and biological implications
Qiqi WANG ; Yuwei ZHAO ; Xue CHEN ; Zhan GAO ; Miao HE
Chinese Journal of Blood Transfusion 2026;39(3):305-316
Objective: To establish a rapid, accurate, and decentralized workflow for bacterial whole-genome sequencing (WGS) and risk profiling within the shelf-life of platelet concentrates, and to characterize the species, virulence, antimicrobial resistance (AMR), and immune evasion mechanisms of co-existing bacteria in qualified platelet products, thereby providing a scientific basis for transfusion safety assessment. Methods: Three units of platelet concentrates, which tested negative by routine bacterial screening, were collected from the Chengdu Blood Center between May and June 2025. Samples were enriched at 37℃under six aerobic and nine anaerobic conditions for 7 days. Using a culturomics strategy, aliquots were plated for isolation on days 1, 3, 5, and 7 to obtain cultivable isolates, with negative culture controls included to exclude contamination. High-molecular-weight genomic DNA was extracted via mechanical grinding, purified, and size-selected. Sequencing libraries were constructed and sequenced on the G-seq500 single-molecule nanopore sequencing platform. Genomes were assembled using Flye and polished with NextPolish, with quality evaluated by BUSCO and CheckM. Taxonomic identification was performed using GTDB-Tk. Functional annotation and database comparisons were conducted to analyze virulence factors, AMR genes, and genes related to immune evasion and environmental adaptation. Results: Viable bacteria were successfully isolated from all three qualified platelet units within their shelf life. The isolates were identified as Bacillus albus, Niallia taxi, and Staphylococcus warneri. Nanopore sequencing generated 92 227-109 813 reads (totaling 680-758 Mb) with an N50 of 7 625-8 584 bp and Q20/Q30 scores of 97%/93%, respectively. All three genomes were assembled into complete circular chromosomes with 1-3 plasmids, achieving >93% completeness. Functional analysis revealed that B. albus carried multiple hemolysins, metalloproteases, and multidrug resistance genes, indicating the highest potential pathogenicity and AMR risk. S. warneri exhibited a typical multidrug resistance profile and regulatory network characteristic of coagulase-negative staphylococci, suggesting intermediate virulence. N. taxi harbored few canonical virulence factors and lacked functional AMR determinants, presenting a "low-virulence, low-resistance" profile. Notably, all three strains were enriched in genes encoding antimicrobial peptide resistance systems (e.g., dltABCD, mprF, GraRS, BceAB) and antioxidant enzymes, suggesting a strong capacity to withstand immune stress in the blood environment. Conclusion: Viable bacteria can be recovered from qualified platelet concentrates that test negative by routine screening. Nanopore WGS enables rapid strain-level identification and comprehensive risk profiling of virulence, resistance, and immune adaptation traits. The functional repertoires of these "co-existing" isolates range from environmental adaptation to potential pathogenicity, representing an underappreciated risk for transfusion-transmitted infections in susceptible recipients.
6.Epidemiological characteristics and spatial-temporal aggregation of scarlet fever in Nantong City in 2009 - 2023
Chao BAO ; Junfeng MIAO ; Enhui ZHAO ; Zhenzhen LIU ; Wuhong ZHANG ; Ye WEI
Journal of Public Health and Preventive Medicine 2026;37(2):40-44
Objective To analyze the epidemiological characteristics and spatial-temporal clustering trend of scarlet fever in Nantong from 2009 to 2023, and to provide a scientific basis for scarlet fever prevention and control. Methods The incidence data of scarlet fever in Nantong from 2009 to 2023 were analyzed. Descriptive analysis, seasonal index method and Joinpoint 5.2.0 software were used to analyze epidemiological characteristics. Spatial-temporal clustering was assessed with SaTScan 10.2.5 software. Results The average annual incidence of scarlet fever in Nantong from 2009 to 2023 was 6.54/100 000. The overall morbidity rate of scarlet fever in Nantong had an increasing trend from 2009 to 2019 with an average annual percentage change of 14.55% (t=3.36,P<0.05). The cases mainly occurred during late spring to early summer and late autumn to early winter. Students, preschool children and scattered children were the main scarlet fever population. The average annual incidence of males was significantly higher than that of females (χ2=7.00, P<0.05). Rugao City, Chongchuan District and Tongzhou District were identified as high-incidence areas, accounting for 76.51% of all reported cases. Spatial-temporal scan analysis indicated that Rugao City and Chongchuan District were primary cluster areas, spanning from 2015 to 2021 (RR=3.77, LLR=1 308.07, P<0.05). Conclusion The number of reported cases of scarlet fever in Nantong City from 2009 to 2023 shows epidemic and spatial clustering, mainly concentrated in the central urban area and adjacent counties (cities). It is necessary to strengthen health education and disease surveillance in high-incidence areas, as well as in key institutions and key populations before epidemic peaks.
7.Mechanism of Bushen Kaixuan Tongluo Prescription in Improving Diabetic Nephropathy Based on cAMP Signaling Pathway
Miao XU ; Baosheng ZHAO ; You WANG ; Yuzhuo CHANG ; Zehao LIU ; Lingling QIN ; Haiyan WANG ; Ming GAO ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):87-96
ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease (DKD) by regulating the cyclic adenosine monophosphate (cAMP) signaling pathway. MethodsThirty specific pathogen-free (SPF) male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L-1 and urinary albumin-creatinine ratio (ACR) ≥ 30 mg·g-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group: the model group, the low-, medium-, and high-dose Bushen Kaixuan Tongluo prescription groups (administered at doses of 7, 14, 28 g·kg-1·d-1 respectively), and the positive drug irbesartan group (administered at a dose of 20 mg·kg-1·d-1). Additionally, six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations, irbesartan, or an equal volume of pure water, and the intervention lasted for 12 weeks. During the experiment, the general conditions, body weight changes, and renal function indicators of the mice were dynamically monitored. After the intervention, a blood glucose meter was used to measure the fasting blood glucose (FBG) of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine (SCr), blood urea nitrogen (BUN), urinary microalbumin (uALB), ACR, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), leptin (LEP), glycosylated serum protein (GSP), and insulin (INS) in the mice. Renal tissues were collected for hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry (IHC) was used to detect the expressions of protein kinase A (PKA) and cAMP response element-binding protein (CREB) in the mice. Western blot analysis was performed to determine the expression levels of PKA, phosphorylated protein kinase A (p-PKA), CREB, phosphorylated cAMP response element-binding protein (p-CREB), and B-cell lymphoma-2 (Bcl-2) proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of PKA, CREB, and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group, the mice in the model group showed listlessness, decreased activity, and a significant increase in body weight (P<0.01). Biochemical indicators revealed that the levels of BUN, uALB, ACR, AST, ALT, TC, TG, FBG, LEP, GSP, and INS were significantly increased (P<0.01), while SCr showed an increasing trend with no statistically significant difference. Compared with the model group, the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN, uALB, ACR, TC, GSP, and INS were significantly decreased (P<0.05), while SCr, AST, ALT, TG, and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane, expansion of the mesangial matrix, and deposition of collagen fibers in the renal tubulointerstitium, and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group, the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased (P<0.01). Compared with the model group, the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased (P<0.01), while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group, the expression levels of p-PKA/PKA, p-CREB/CREB, and Bcl-2 in the model group were significantly decreased (P<0.05). Compared with the model group, the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased (P<0.01). Real-time PCR results showed that compared with the blank group, the mRNA expressions of PKA, CREB, and Bcl-2 in the model group were significantly down-regulated (P<0.05). Compared with the model group, the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated (P<0.05). ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice, correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress, thereby protecting renal function.
8.Fabrication and evaluation of an inositol hexaphosphate-zinc hydrogel with dual capabilities of self-mineralization and osteoinduction
LIU Mingyi ; MIAO Xiaoyu ; CAI Yunfan ; WANG Yan ; SUN Xiaotang ; KANG Jingrui ; ZHAO Yao ; NIU Lina
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(1):29-40
Objective:
To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials.
Methods:
The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group
Results:
The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group.
Conclusion
The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.
9.Regulation of Relevant Signaling Pathways by Traditional Chinese Medicine in Intervention of Pancreatic Cancer: A Review
Quanyou ZHAO ; Conghui ZHAO ; Yu ZHANG ; Yiping FU ; Yuting LIU ; Xiaoran WANG ; Zhanzhan LI ; Mingsan MIAO ; Li BAI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):280-289
Pancreatic cancer is a highly malignant solid tumor of the digestive system with extremely poor treatment prognosis. Although its incidence rate is low, its mortality rate is extremely high. In recent years, the number of diagnosed cases worldwide has continued to rise, making pancreatic cancer the sixth leading cause of cancer-related deaths globally. Currently, clinical treatment primarily relies on operation and chemotherapy to suppress tumors. However, these approaches face challenges such as suboptimal efficacy, high postoperative recurrence rates, and severe adverse reactions. Therefore, identifying safe and effective treatment modalities remains a pressing challenge for the medical community. In recent years, research on traditional Chinese medicine (TCM) interventions for pancreatic cancer has increased significantly. Multiple studies have shown that single-herb TCM, TCM formulas, and their derived single compounds can regulate the levels of tumor cell signaling pathways through multiple action targets. They inhibit the development and progression of pancreatic cancer by inhibiting cancer cell proliferation, promoting cell apoptosis, inhibiting tumor angiogenesis, reducing cancer cell invasion and migration capabilities, regulating the cell cycle, and modulating the tumor microenvironment. Additionally, TCM has the advantages of significantly enhancing the anticancer efficacy of chemotherapy drugs and causing fewer adverse reactions. However, the specific action mechanisms by which TCM intervenes in pancreatic cancer remain unclear. Further extensive research is still needed to validate the role of regulating classical signaling pathways such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Wnt/β-catenin, nuclear transcription factor-κB (NF-κB), notch, and hedgehog in the treatment of pancreatic cancer. Therefore, this paper reviewed Chinese and international studies on TCM intervention in pancreatic cancer through relevant signaling pathways in recent years, summarized the potential action mechanisms of TCM in the treatment of pancreatic cancer, and provided references for related research in the future.
10.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.


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