1.Traditional Chinese Medicine Treats Esophageal Cancer via PI3K/Akt Signaling Pathway: A Review
Wei GUO ; Chen PENG ; Yikun WANG ; Zixuan YU ; Jintao LIU ; Jing DING ; Yijing LI ; Hongxin SUN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):302-311
Esophageal cancer (EC) is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, as one of the key oncogenic pathways, can promote the cell cycle progression, proliferation, migration, and invasion, induce chemoresistance, and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine (TCM), with the advantages of targeting multiple points with multiple components to delay cancer progression, can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum, spore powder of Ganoderma lucidum without spore coat, extract of Celastrus orbiculatus, root extract of Taraxacum, and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids, terpenoids, saponins, phenols, polysaccharides, alkaloids, and other compounds. TCM compound prescriptions with such effect include Qige San, Huqi San, Xuanfu Daizhetang, Tongyoutang and its decomposed prescriptions, Liujunzi Tang, and Xishenzhi Formula. In addition, TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions, aiming to provide reference for the research and clinical application of new drugs for EC.
2.Mechanism of Danggui Shaoyaosan in Improving Glomerulosclerosis in db/db Mice via SIRT1/HIF-1α/VLDLr Signaling Pathway
Ruijia LI ; Zixuan WANG ; Shilong GUO ; Jing LI ; Qianqian ZHANG ; Wen DONG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):11-18
ObjectiveTo investigate the potential mechanism of Danggui Shaoyaosan (DSS) in ameliorating renal injury in db/db mice. MethodsThirty 8-week-old specific pathogen-free (SPF)-grade male db/db mice and six db/m mice were acclimated for one week. Urinary microalbumin and blood glucose levels were measured weekly in both db/db and db/m mice. Successful modeling was determined by significantly higher microalbuminuria in db/db mice compared to db/m mice and a fasting blood glucose ≥16.7 mmol·L-1. The 30 db/db mice were randomly divided into five groups: the model group, the irbesartan (IBN) group, and three DSS dose groups (low-, medium-, and high-dose DSS groups, administered at 16.77, 33.54, 67.08 g·kg-1·d-1, respectively). Additionally, the six db/m mice served as the normal control group. The IBN group received irbesartan at 0.025 g·kg-1·d-1 by gavage, while the three DSS groups received DSS at 16.77, 33.54, and 67.08 g·kg-1·d-1 by gavage, respectively. The normal and model groups were administered with an equivalent volume of normal saline by gavage. All interventions lasted for 8 consecutive weeks. After intervention, serum creatinine (SCr), blood urea nitrogen (BUN), urinary total protein (UTP), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were measured to evaluate the therapeutic efficacy of the treatments. Renal histopathological changes were observed with hematoxylin-eosin (HE) staining. Western blot was used to detect the protein expression of silencing information regulator 1 (SIRT1), hypoxia-inducible factor-1α (HIF-1α), very low-density lipoprotein receptor (VLDLr), and cluster of differentiation 31 (CD31). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA levels of HIF-1α and VLDLr. Immunohistochemistry was used to observe the expression and distribution of HIF-1α and Caspase-3. ResultsCompared to the normal group, the model group showed significantly increased SCr, BUN, UTP, TG, and LDL-C. HE staining revealed glomerulosclerosis, mesangial matrix hyperplasia, capillary loop distortion and thickening, with extensive inflammatory cell infiltration. Protein expression of SIRT1 and CD31 significantly decreased (P<0.05), while HIF-1α and VLDLr protein and mRNA levels increased (P<0.05). Immunohistochemistry showed increased expression of HIF-1α and Caspase-3 (P<0.05), indicating hypoxia and apoptosis in renal cells. In all treatment groups, SCr, BUN, TG, and LDL-C were significantly reduced compared to the model group (P<0.05), and UTP was significantly improved in the medium-dose DSS group (P<0.05). Renal tissue structure and morphology were improved, inflammatory cells were reduced, and no vascular hyaline degeneration was observed. SIRT1 and CD31 protein expression was elevated to varying degrees compared to the model group (P<0.05), while HIF-1α and VLDLr protein and mRNA levels decreased (P<0.05). Immunohistochemistry showed reduced expression of HIF-1α and Caspase-3 in all treatment groups (P<0.05), with the most significant improvement observed in the IBN group and medium-dose DSS group (P<0.05). ConclusionDSS can effectively ameliorate glomerulosclerosis and lipid deposition in db/db mice, and its mechanism may involve the SIRT1/HIF-1α/VLDLr signaling pathway.
3.Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells
Ruijia LI ; Zixuan WANG ; Shilong GUO ; Sen YANG ; Jing LI ; Qianqian ZHANG ; Wen DONG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):28-35
ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan (DSS) on renal injury in db/db mice and its impact on endoplasmic reticulum stress (ERS) in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week, after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease (DKD) model. The model mice were randomly divided into a model group, an irbesartan group, and three DSS treatment groups with different doses (16.77, 33.54, and 67.08 g·kg-1·d-1). A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention, general conditions were observed. Serum cystatin C (Cys-C), 24-hour urinary total protein (24 h-UTP), 24-hour urinary microalbumin (24 h-UMA), urinary creatinine (Ucr), and urea nitrogen (UUN) were measured. Transmission electron microscopy (TEM) was used to observe glomerular basement membrane (GBM) and ultrastructural changes of the endoplasmic reticulum (ER) in glomerular endothelial cells. Western blot, real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78, CHOP, and related markers. ResultsCompared with the normal group, the mice in the model group showed curled posture, sluggish response, poor fur condition, increased levels of Cys-C, 24 h-UTP, 24 h-UMA, and UUN (P<0.05), while Ucr decreased (P<0.05). The GBM was significantly thickened, with podocyte and foot process fusion. The protein expressions of GRP78, CHOP, and ATF6 were significantly upregulated (P<0.05), the mRNA levels of GRP78 and CHOP increased (P<0.05), and immunohistochemistry showed an enhanced GRP78 signal (P<0.05). After treatment, the mice exhibited improved behavior, normalized GBM and podocyte structure, improved ER morphology and markedly better biochemical indicators. Western blot, Real-time PCR, and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups (P<0.05), suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice, possibly by regulating ERS in glomerular endothelial cells, although the underlying signaling mechanisms require further investigation.
4.Herbal Textual Research on Cynanchi Atrati Radix et Rhizoma in Famous Classical Formulas
Xiaoqi JING ; Minna GUO ; Haihua WANG ; Juan LI ; Fusheng ZHANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):208-216
This article systematically reviews and verifies the name, origin, production area, quality evaluation, harvesting, processing and other aspects of Cynanchi Atrati Radix et Rhizoma(CARR) by consulting relevant ancient and modern literature, in order to provide a basis for the development and utilization of famous classical formulas containing this herb. Through textual research, Baiwei has been the official name for CARR, though it also bears alternative names such as Chuncao, Popo Zhenxianbao, Longdan Baiwei. The mainstream base is the roots and rhizomes of Cynanchum atratum. Historical records indicate primary producing areas include Shandong, Anhui, Jiangsu, Shaanxi and Shanxi. Since the late Ming dynasty, varieties from Juxian, Yishui and Rizhao in Shandong have been highly regarded as authentic, commonly known as eastern Baiwei. Since modern times, its quality has been summarized as fine, slender, and straight fibrous roots, pale yellow exterior, whiter interior, and dryness with easy breakability are considered superior. The harvesting time before the Song dynasty was on the third day of the third lunar month, but after the Song dynasty, harvesting was possible in both spring and autumn. The initial processing methods of CARR in ancient times included drying in the shade, removing Lu(the little rhizomes which are on tap of roots), and removing mustaches, modern methods involve washing and sun-drying. During the Northern and Southern dynasties, processing methods included steaming. In the Song dynasty, drying and light stir-frying were predominant, while wine washing emerged in the Ming dynasty. Modern practices primarily involve using raw, stir-frying or honey processing. Regarding the medicinal properties of CARR, both ancient and modern texts agree it has a bitter and salty taste and is non-toxic. Records prior to the Qing dynasty predominantly describe its nature as extremely cold, while mainstream herbal texts after the Qing dynasty generally characterize it as cold. Before the Ming dynasty, there were no records of its meridian tropism. It was not until the Qing dynasty that it was recorded in the lung meridian. Modern records mainly refer to the stomach, liver, and kidney meridians. Throughout history, its main functions have been to clear heat, diuresis, nourish Yin, and replenish essence, primarily treating Yin deficiency and fever syndrome. Based on the research results, it is suggested that when developing famous classical formulas containing CARR, the dried roots and rhizomes of C. atratum can be selected as its medicinal source. If there are no specific processing requirements, raw products can be selected as medicine. If the processing requirements are specified, corresponding processed products can be selected as medicine according to the original formula requirements.
5.Influencing Factors of Urate Crystal Deposition in Patients with Hyperuricemia and Prediction Model of TCM Syndrome Types-inflammatory Indicators
Jiaqi XU ; Bin AI ; Chao LIN ; Qiaoxuan LIN ; Changning LI ; Jing CAI ; Yan XIAO ; Jiemei GUO ; Youxin SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):66-73
ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia (HUA), and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine (TCM) syndromes, so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group (143 cases) and a crystal deposition-negative group (88 cases) according to the results of dual-energy computed tomography (CT). Sociodemographic data, living habits, serum uric acid levels, and inflammatory indicators of the enrolled patients were collcted, and TCM syndrome differentiation was performed. Furthermore, univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition, the receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males, age, body mass index, proportion of mental labor, rate of low water intake, and rate of high-sugar beverage consumption (P<0.05),whereas no significant difference in low exercise intensity was found between the two groups. Furthermore, compared with the negative group, the positive group had higher serum uric acid level, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), but lower systemic immune-inflammation index (SIRI) (P<0.05). Regarding the distribution of TCM syndromes, the positive group was dominated by the dampness-heat accumulation syndrome (55/143,38.46%), while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome (44/88,50.00%). Multivariate Logistic regression analysis revealed that high-sugar beverage consumption, elevated NLR, and elevated PLR were risk factors for urate crystal deposition [odd ratio (OR) = 8.002, 5.377, 1.034, respectively; 95% CI 1.572-40.732, 2.179-13.270, 1.013-1.054,all P<0.05], while SIRI was a protective factor (OR = 0.869, 95% CI 0.778-0.971, P<0.05). In the positive group, patients with the dampness-heat accumulation syndrome exhibited the highest NLR, while the lowest PLR and SIRI, showing statistically significant differences with those of other syndromes (all P<0.05). In addition, ROC curve analysis indicated that for the dampness-heat accumulation syndrome, the combined "NLR + PLR" model had an area under the curve (AUC) of 0.901 (95% CI 0.850-0.951, P<0.01), with a sensitivity of 89.1% and a specificity of 79.5%; for the blood stasis-heat obstruction syndrome, the combined "NLR + PLR" model had an AUC of 0.880 (95% CI 0.825-0.934, P<0.01), with a sensitivity of 100.0% and a specificity of 67.3%; for the liver-kidney Yin-deficiency syndrome, the single PLR model had an AUC of 0.842 (95% CI 0.731-0.952, P<0.01), with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile, TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.
6.Construction and application of anti-tumor drug prescription review decision-support system in a large general hospital
Jing ZANG ; Run GAN ; Qi YANG ; Yan CHEN ; Cheng GUO ; Jianping ZHANG ; Fengqian LI ; Quanjun YANG
China Pharmacy 2026;37(6):794-799
OBJECTIVE To introduce the development of an intelligent prescription review decision-support system for anti-tumor drugs and assess its clinical application outcomes. METHODS Relevant data sources, including national and local pharmaceutical administration policies, clinical practice guidelines/consensus, hospital information systems data, and genetic testing results, were integrated. Adhering to the principles of structure, standardization and dynamic updating, a knowledge base covering chemotherapeutic, targeted and immunotherapeutic agents was constructed using a dual-dimensional modeling approach that combined “drug attributes” and “clinical contexts”. This knowledge base was then embedded into the hospital’s electronic medical order system to establish the prescription review decision-support system. The application and performance of the system were evaluated at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. RESULTS A knowledge base containing 18 318 prescription review rules for anti-tumor drugs was constructed, and a closed-loop prescription review system was successfully established, encompassing pre-prescription real-time intervention, in-process interactive review, and post-prescription evaluation and analysis. From 2021 to 2024, the system generated a total of 57 879 alerts for prescriptions of five typical categories of anti-tumor drugs. For platinum-containing prescriptions, 22 577 alerts were generated, with Cisplatin for injection (lyophilized) being the most frequently alerted drug (13 445 alerts), and “ototoxicity risk due to combined use” alerts remained high (7 682 alerts). For methotrexate-containing prescriptions, 3 721 alerts were recorded, primarily related to “precaution-related issues” (76.4%, 2 843/3 721). For doxorubicin-containing prescriptions, 17 301 alerts were triggered, primarily related to “dosage and administration” (14 315 alerts). For human epidermal growth factor receptor 2-targeted agents-containing prescriptions, 1 007 alerts were issued, mostly related to “reimbursement restrictions” (956 alerts). For programmed death-1/programmed death-ligand 1 inhibitors-containing prescriptions, the alerts increased year by year, totaling 13 273 alerts, primarily related to “inappropriate indication” (9 118 alerts). Over the 4 years, the physician response rates to system alerts were 21.4%, 27.1%, 33.5% and 51.6%, respectively. CONCLUSIONS An intelligent decision-support system for anti-tumor drug prescription review, encompassing a closed-loop process of “real-time pre-event intervention, interactive in-event prescription review, post-event evaluation and analysis”, has been successfully constructed and implemented throughout the entire workflow. There is a discernible trend in this hospital, where the focus on monitoring anti-tumor drugs is shifting towards immunotherapy drugs. Additionally, the acceptance rate of physicians regarding prescription review opinions has been steadily increasing year by year.
7.Factors affecting and identification of key environmental determinants of the Oncomelania hupensis snail density in the Yangtze River Delta based on machine learning models
Yinlong LI ; Qin LI ; Suying GUO ; Shizhen LI ; Lijuan ZHANG ; Chunli CAO ; Jing XU
Chinese Journal of Schistosomiasis Control 2026;38(1):14-19
Objective To identify factors affecting and key environmental factors of the Oncomelania hupensis snail density in the Yangtze River Delta region using machine learning methods. Methods Administrative village-level O. hupensis snail survey data in the Yangtze River Delta (including Shanghai Municipality, Jiangsu Province, Zhejiang Province and Anhui Province) from 2011 to 2021 were retrieved from the Information Management System for Parasitic Disease Control of Chinese Center for Disease Control and Prevention. Environmental factor data were captured from the Google Earth Engine platform, including elevation, slope, terrain, normalized difference vegetation index (NDVI), vegetation type, soil type, total petroleum hydrocarbon (TPH), ammonium nitrogen, inorganic nitrogen, dissolved oxygen, pH of water, chemical oxygen demand (COD) and inorganic phosphorus, and climatic factor data in the study region were retrieved from the Copernicus Climate Data Store, including annual precipitation, aridity index and annual mean temperature (AMT). O. hupensis snail survey data in the Yangtze River Delta region from 2011 to 2021 were randomly divided into a training set (70%) and a test set (30%), and five machine learning models were selected for machine learning model construction and comparative analysis of the O. hupensis snail density using the software R 4.3.0, including random forest (RF), eXtreme gradient boosting (XGBoost), support vector machine (SVM), gradient boosting machine (GBM) and neural network (NN). The XGBoost model was employed to construct a predictive model for the O. hupensis snail density, and the impact of each environmental factor on O. hupensis snail distribution was quantified. The SHapley Additive exPlanations (SHAPs) values were calculated to estimate the average contribution of each variable to the model prediction, and the core environmental factors affecting the O. hupensis snail population density were screened. Results Among the five machine learning models, the XGBoost model exhibited the optimal comprehensive performance, with the coefficient of determination (R2) of 0.855, mean squared error (MSE) of 0.188, root mean squared error (RMSE) of 0.434 and mean absolute error (MAE) of 0.155, respectively. Analysis of factors affecting the O. hupensis snail density with the XGBoost model showed that among the 16 environmental factors, the top four high-impact factors ranked by SHAPs values included annual precipitation, elevation, aridity index and NDVI, with cumulative SHAPs contributions of 75%, which was higher than that of other environmental factors. If NDVI was higher than 0.6, the O. hupensis snail density increased with NDVI and peaked if NDVI was 0.8 (1.60 snails/0.1 m2). The O. hupensis snail density increased with elevation if the elevation ranged from 14 to 40 m, and slowly rose if the annual precipitation ranged from 900 to 1 300 mm, and then increased rapidly to the peak (1.52 snails/0.1 m2) if the annual precipitation ranged from 1 300 to 1 500 mm. In addition, the O. hupensis snail density increased rapidly to the maximum (1.60 snails/0.1 m2) if the aridity index ranged from 0.8 to 1.1, and decreased gradually if the aridity index exceeded 1.1. Conclusions The XGBoost model shows excellent performance in prediction of the O. hupensis snail density and identification of key environmental factors in the Yangtze River Delta region. Annual precipitation, elevation, aridity index and NDVI are key environmental factors affecting the distribution and density of O. hupensis snails in the Yangtze River Delta region.
8.Intervention Mechanism of Guizhi Fulingwan in Delaying Colitis-associated Colon Cancer via Modulating and Restoring MDSCs and Reshaping Immune Microenvironment
Yanwei HAO ; Chunrun LI ; Zhengwu QU ; Junmei TANG ; Jing GUO ; Yi ZHANG ; Fengming YOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):185-194
ObjectiveThis paper aims to investigate the efficacy and related actions of Guizhi Fulingwan in intervening in the mice with colitis-associated colon cancer (CAC) based on the immunosuppressive microenvironment associated with myeloid-derived suppressor cells (MDSCs). MethodsSixty male C57BL/6 mice were randomly assigned to a blank group, a model group, an aspirin group (0.04 g·kg-1), and low-, medium-, and high-dose Guizhi Fulingwan groups (4.87, 9.75, and 19.50 g·kg-1), with ten mice per group. The CAC mouse model was established via combined induction of azoxymethane (AOM)/dextran sulphate sodium (DSS). Drug intervention commenced in week five, with continuous intragastric administration for nine weeks. The food intake, body weight, fecal characteristics, and haematochezia were observed and recorded, and disease activity index (DAI) scores were calculated according to scoring criteria. Hematoxylin and eosin (HE) staining was used to observe the histopathological changes in the colon tissues of the mice. Immunohistochemistry was used to determine proliferating cell nuclear antigen-67 (Ki67) expression in the colon tissues, and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) in the serum of the mice. Flow cytometry was employed to determine the proportion levels of MDSCs, CD4+ T cells, and CD8+ T cells in the spleen tissues of the mice. The mRNA expressions of MDSC-associated effector molecules, including arginase 1 (Arg1) and inducible nitric oxide synthase (iNOS), were detected by real-time quantitative polymerase chain reaction (Real-time PCR). After that, an in vitro co-culture model of MDSCs and CD8+ T cells was established, and drug-containing serum of Guizhi Fulingwan was used for intervention. The Flow cytometry was employed to assess the effects of drug-containing serum of Guizhi Fulingwan with different concentrations on the levels of reactive oxygen species (ROS) and iNOS in MDSCs and the proliferation of CD8+ T cells. The levels of granzyme B (GZMB) and interferon-γ (IFN-γ) in cell supernatant were detected by ELISA. ResultsCompared with those in the control group, the mice in the model group exhibited significantly reduced body weight, elevated DAI scores, shortened colon length (P<0.01), increased number of tumors and Ki67 expression (P<0.01), and significantly elevated contents of IL-6, IL-1β, and TNF-α in the serum (P<0.01). Significant increases in the number of MDSCs were observed in mouse spleens, alongside marked reductions in the levels of CD4+ T and CD8+ T cells (P<0.01). Furthermore, the mRNA expressions of MDSC function-associated effector molecules Arg1 and iNOS were significantly upregulated (P<0.01). Compared with those in the model group, the mice in the middle-dose Guizhi Fulingwan group exhibited increased body weight and significantly decreased DAI scores (P<0.05, P<0.01). The mice in the middle- and high-dose Guizhi Fulingwan groups exhibited significantly improved colon shortening, significantly decreased number of tumors and Ki67 expression (P<0.05, P<0.01), and significantly decreased contents of IL-6, IL-1β, and TNF-α in the serum (P<0.05, P<0.01). Furthermore, administration of Guizhi Fulingwan markedly reduced MDSC infiltration in the spleen of the mice, with different degrees of increase in the levels of both CD4+ T and CD8+ T cells (P<0.05, P<0.01), alongside significant decreases in the mRNA expressions of Arg1 and iNOS (P<0.05, P<0.01). In vitro cell co-culture shows that administration of drug-containing serum of Guizhi Fulingwan significantly decreases the activity levels of ROS and iNOS in MDSCs and promotes the proliferation of CD8+ T cells and the secretion of GZMB and IFN-γ (P<0.05, P<0.01). ConclusionGuizhi Fulingwan can reduce pro-inflammatory cytokine secretion and inhibit tumor proliferation in the colon tissues of CAC mice. Its potential mechanism may involve reducing MDSC infiltration, enhancing effector T cells, particularly CD8+ T cell response, and improving the tumor immunosuppressive microenvironment.
9.Construction of A Nomogram Prognostic Model Based on Pretreatment Inflammatory Indicator for Esophageal Squamous Cell Carcinoma Patients Treated with Radical Radiotherapy
Shenbo FU ; Long JIN ; Jing LIANG ; Junjun GUO ; Yu CHE ; Chenyang LI ; Yong CHEN
Cancer Research on Prevention and Treatment 2025;52(2):142-150
Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.
10.Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase.
Jing GUO ; Jihong ZHENG ; Ruixia LI ; Jindong YAO ; He ZHANG ; Xu WANG ; Chao ZHANG
Journal of Zhejiang University. Science. B 2025;26(6):589-608
Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here, we generated glutaminyl-peptide cyclotransferase-knockout (Qpct-/-) mice utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform and identified Qpct as a novel anti-angiogenic factor in regulating mouse placentation. Compared with Qpct+/+ mice, placentae and embryos (Qpct-/+ and Qpct-/-) showed significant overgrowth at embryonic Day 12.5 (E12.5), E15.5, and E18.5. Using single-cell transcriptome analysis of 32 309 cells from Qpct+/+ and Qpct-/- mouse placentae, we identified 13 cell clusters via single-nucleus RNA sequencing (snRNA-seq) (8880 Qpct+/+ and 13 577 Qpct-/- cells) and 20 cell clusters via single-cell RNA sequencing (scRNA-seq) (6567 Qpct+/+ and 3285 Qpct-/- cells). Furthermore, we observed a global up-regulation of pro-angiogenic genes in the Qpct-/- background. Immunohistochemistry assays revealed a notable increase in the number of blood vessels in the decidual and labyrinthine layers of E15.5 Qpct-/+ and Qpct-/- mice. Moreover, the elevation of multiple pairs of ligand-receptor interactions was observed in decidual cells, endothelial cells, and macrophages, promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternal Qpct leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.
Animals
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Female
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Pregnancy
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Mice
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Placentation/genetics*
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Single-Cell Analysis
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Gene Expression Profiling
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Mice, Knockout
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Transcriptome
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Placenta/blood supply*
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Neovascularization, Pathologic/genetics*
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Genomic Imprinting
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Single-Cell Gene Expression Analysis
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Angiogenesis

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