ObjectiveTo observe the effect of Weichang'an prescription-containing serum on ferroptosis of human gastric cancer cells and explore the possible mechanism. MethodsSD rats were administrated with 18， 36， 72 g·kg^-1·d^-1 Weichang'an prescription by gavage for preparation of serum samples containing different doses of Weichang'an prescription， which were then used to treat MKN-45 cells. The cell proliferation was examined by the cell counting kit-8 （CCK-8）. In addition， inhibitors of apoptosis， necroptosis， and ferroptosis were added， and the survival of the cells treated with the serum samples was observed. The fluorescent probe dichlorodihydrofluorescein diacetate （DCF-DA） and the lipid peroxidation sensor C11-BODIPY were employed to detect the intracellular levels of reactive oxygen species （ROS） and lipid peroxidation， respectively. The levels of ferrous ion （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time PCR and Western blotting were employed to determine the expression of nuclear factor erythroid 2-related factor 2 （Nrf2）， aldo-keto reductase family 1 member B1 （AKR1B1）， glutathione peroxidase 4 （GPX4）， acyl-CoA synthetase long-chain family member 4 （ACSL4）， signal transducer and activator of transcription 3 （STAT3）， and mitogen-activated protein kinase （MAPK）. ResultsCompared with the blank group， Weichang'an prescription-containing serum decreased the viability of MKN-45 cells （P<0.05， P<0.01） in a time- and dose-dependent manner. Compared with the Weichang'an prescription group， the apoptosis inhibitor+Weichang'an prescription group and the ferroptosis inhibitor+Weichang'an prescription group showed increased cell viability （P<0.05， P<0.01）. Compared with the blank group， Weichang'an prescription elevated the levels of ROS， lipid peroxidation， and intracellular Fe²⁺ and MDA （P<0.05， P<0.01） and lowered the level of GSH （P<0.05， P<0.01） in a dose-dependent manner. Compared with the blank group， Weichang'an prescription down-regulated the mRNA and protein levels of Nrf2， AKR1B1， and GPX4 （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of ACSL4 （P<0.05， P<0.01） in a dose-dependent manner. Compared with the blank group， Weichang'an prescription down-regulated the protein levels of p-STAT3 and p-ERK （P<0.05， P<0.01） in a dose-dependent manner. ConclusionThe Weichang'an prescription-containing serum can promote the ferroptosis and inhibit the proliferation of MKN-45 cells by regulating the STAT3 and MAPK pathways.

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

ObjectiveTo explore the evolution principles of symptoms including deficiency， phlegm and blood stasis， and of the functional near-infrared spectroscopy （fNIRS） cerebral hemodynamic characteristics at various stages in patients of Alzheimer's disease. MethodsA total of 497 patients with complaint of memory loss were included， and were divided into subjective cognitive decline （SCD） group （198 participants）， mild cognitive impairment （MCI） group （228 participants） and dementia （AD） group （71 participants）. Neuropsychological evaluation， traditional Chinese medicine （TCM） syndrome investigation， and fNIRS data collection of prefrontal cortex were performed in each group. Descriptive statistics were used to analyze the distribution of TCM syndromes and the difference of TCM syndrome scores in each group； logistic regression was used to analyze the influence of TCM syndromes on the incidence of the patients； association rules were used to analyze the TCM syndromes of the patients； the hemodynamic characteristics of fNIRS in the prefrontal cortex of each group were compared. ResultsKidney essence deficiency syndrome was the dominant syndrome in all stages of AD. There were statistically significant differences in the distribution frequency of kidney essence deficiency， phlegm turbidity obstructing orifices， blood stasis obstructing collaterals， qi and blood deficiency， heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes among the three groups （P＜0.01）， and the scores of kidney essence deficiency syndrome among the three groups were statistically significant （P＜0.01）. Logistic regression analysis showed that kidney essence deficiency， and qi and blood deficiency syndromes were the main risk factors for the SCD group （P＜0.05）， phlegm turbidity obstructing orifices syndrome was the main risk factor for the MCI group （P＜0.05）， and heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes were the main risk factors for the AD group （P＜0.05）. The association rule analysis showed that the combination of kidney essence deficiency plus phlegm turbidity obstructing orifices had the highest support （33.33%） in the SCD group， and the combination of kidney essence deficiency plus blood stasis obstructing collaterals had the highest support （32.90% and 52.13%） in both the MCI and AD group. The prefrontal fNIRS results showed that the mean ∆HbO₂ concentration in the left dorsolateral prefrontal cortex （LDLPFC） decreased sequentially among the three groups （P＜0.05）， and the mean ∆HbO₂ concentration in the LDLPFC was negatively correlated with the MoCA score among the three groups （r = -0.142， P＜0.05）. Further analysis showed that the mean ∆HbO₂ concentration in the LDLPFC of patients with kidney essence deficiency syndrome were statistically significant differences among the three groups （P＜0.05）. ConclusionKidney deficiency is the basis of the pathogenesis of AD， and the key brain area damaged is the LDLPFC. Turbid pathogens such as phlegm and blood stasis are the pathological factors that aggravate the disease， and the syndromes of AD show the evolution law of deficiency and excess as “kidney deficiency→phlegm turbidity→blood stasis→turbid toxin”. The changes in prefrontal hemodynamics based on fNIRS are consistent with the changes in the characteristics of symptoms， which can be used to assess the degree of cognitive impairment in AD patients.

Cathartic colon （CC） is a common and refractory digestive system disease， with the pathogenesis not fully clarified. The effective therapies other than laxatives and surgery remain to be developed for CC. Therefore， establishing the CC animal models that fit the disease characteristics of western medicine and syndrome characteristics of traditional Chinese medicine （TCM） is an important link to promote the research on this disease. The fitting degree of animal models with the latest Chinese and western medical diagnostic criteria is an indicator to assess the effectiveness of the animal models in simulating the disease characteristics of western medicine and syndrome characteristics of TCM. The literature review showed that the model animals， drugs and their dosage forms， doses， administration methods， and modeling period of CC varied in different studies， and the available CC animal models presented different fitting degrees with the disease characteristics of western medicine and syndrome characteristics of TCM. Rats were the preferred animals for the modeling of CC. Rhei Radix et Rhizoma preparations were commonly used for model inducing， which， however， may cause water electrolyte disorders， decreased immunity， and even death of animals at the late stage of modeling. The animals were modeled by gradually increasing the starting dose， while the starting dose and increasing dose varied. The maintenance dose was determined based on 50% of the animals having loose stools， and the end for a cycle was determined as the time when loose stools disappeared in 80% of animals. The modeling always lasted for 2-3 cycles， approximately 2-4 months. The CC models established with Rhei Radix et Rhizoma granules and rhein had high fitting degrees with the disease and syndrome characteristics. In addition， the CC animal models of TCM syndromes were still in the exploration stage. There were only the animal models of four TCM syndromes： liver depression and spleen deficiency， both Qi and Yin deficiency， Qi stagnation and blood stasis， and spleen and kidney deficiency. Efforts should be made to establish the animal models that meet the characteristics of disease of western medicine and syndromes of TCM， so as to facilitate the research on CC mechanism and drug development.

ObjectiveTo collect and screen records concerning the spleen and stomach diseases and syndromes in ancient books of traditional Chinese medicine （TCM） using an automated framework and to systematically explore the concept evolution of spleen and stomach diseases and syndromes using the visualization method. MethodA total of 1 224 kinds of ancient book data in the Ancient Books of Traditional Chinese Medicine Database （V2.1） were analyzed using the automated testing tool Selenium WebDriver with the Python 3.8 programming language and the etree library of Lxml for automatic collection and statistics of the "book title" "author" "classification" "dynasty" "completion time"， and "informative abstract". After being checked and collated， the collected data were visually analyzed with Tableau （V2020.1.3） for figuring out the concept evolution of spleen and stomach diseases and syndromes in the past dynasties from the perspectives of symptoms and signs， etiology and pathogenesis， principle-method-recipe-medicinal， and prognosis. ResultA total of 7 203 clauses were automatically collected from 989 ancient books. It was found that in the pre-Qin period， there were few ancient books related to the spleen and stomach diseases and syndromes， and the understandings were confined to the superficial symptoms or signs and the basic etiology and pathogenesis. From the Han to Sui and Tang dynasties， the related concepts gradually increased and the descriptions about the manifestations are more detailed than those in previous dynasties. The etiology， diagnosis， and treatment system of the spleen and stomach diseases and syndromes were further perfected. In the Song， Jin， and Yuan dynasties， such concepts as independent signs，symptoms， as well as nature and location of spleen and stomach diseases and syndromes were enriched. In the Ming and Qing dynasties， a TCM syndrome differentiation and treatment system for spleen and stomach diseases and syndromes was formed， and the related concepts were gradually simplified and unified. ConclusionThe concepts of spleen and stomach diseases and syndromes have undergone an evolution from simplicity to complexity and then back to simplicity. There are numerous ancient books discussing the concepts of spleen and stomach diseases and syndromes， exhibiting a fluctuating yet rising trend with time. The automated framework enables the construction of a lightweight database of spleen and stomach diseases and syndromes. Based on data visualization， the concept evolution of the spleen and stomach diseases and syndromes from ancient times to the present has been efficiently uncovered， which is conducive to tracing the origin and development of spleen and stomach diseases and syndromes in TCM. This has provided reference for related research of spleen and stomach diseases in modern Chinese medicine.

Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.

Objective:To investigate the blocking effect of non-competitive N-methyl-D-aspartic acid(NMDA) receptor antagonist Memantine on glutamate abnormal signal transmission in immature white matter induced by ischemia in vitro and in vivo. Methods:The oligodendrocyte (OL) precursor oxygen glucose deprivation (OGD) cell models of 2-day-old newborn rats were prepared and divided into the normal control group, the OGD group and the Memantine group.The extracellular glutamate level of the OL precursor was measured by high performance liquid chromatography, while the concentration of intracellular calcium and the apoptosis rate of OL precursor were detected by flow cytometry.The animal models of ischemic periventricular leukomalacia (PVL) were established and divided into the sham group, the PVL group and the Memantine group.The pathological evaluation of white matter was performed under light microscope.The positive OL expression rate of myelin basic protein(MBP) was detected by immunohistoche-mistry.The myelination of white matter was evaluated under electron microscope.Results:Compared with the normal control group in vitro, the OGD group had a higher extracellular glutamate level of the OL precursor [(24.60±2.42) μmol/L vs.(9.49±1.08) μmol/L, t=9.28, P<0.01], a higher intracellular calcium concentration [(32.9±6.9)% vs.(6.9±3.5)%, t=4.41, P<0.01], a higher apoptosis rate of the OL precursor [(24.77±2.05)% vs.(6.65±1.39)%, t=15.01, P<0.01]. After treatment with Memantine, the extracellular glutamate level [(14.70±1.70) μmol/L, t=5.68, P<0.01], the intracellular calcium concentration [(23.1±2.0)%, t=6.13, P<0.01], and the apoptosis rate of the OL precursor [(11.80±2.06)%, t=5.18, P<0.01] decreased significantly.Compared with the sham group in vivo, the white matter of the PVL group showed mild or severe pathological changes, and the PVL group had a lower MBP-positive OL expression rate in the white matter [(5.94±1.37)% vs.(15.40±3.22)%, t=4.63, P<0.01]less myelin sheaths (4.00±1.00 vs.14.67±2.70, t=6.11, P<0.01) and thinner myelin sheaths [(33.83±3.21) nm vs.(79.67±6.45) nm , t=10.43, P<0.01]. After the treatment with Memantine, the number of myelin sheaths (10.30±1.50, t=6.01, P<0.01), the thickness of myelin sheaths [(57.21±4.05) nm, t=7.47, P<0.01], and the pathological changes in the white matter of newborn rats ( Z=88.479, P<0.01) all improved markedly, and the MBP positive OL expression rate in the cerebral white matter [(11.02±1.35)%, t=4.40, P<0.05] also increased significantly. Conclusions:Ischemia-induced abnormal signal transmission of glutamate in immature white matter is the important pathway leading to ischemic PVL.Memantine can effectively block the abnormal signal transmission and thus may probably provide a new approach for the effective prevention and treatment of PVL in premature infants.

Objective::To observe the effect of Jianpi Qingchang decoction on hormone withdrawal in patients with hormone-dependent spleen deficiency damp-heat ulcerative colitis. Method::The 60 patients with hormone-dependent ulcerative colitis with spleen deficiency and damp-heat were selected and collected from the outpatient department and the inpatient department of Longhua Hospital, Shanghai University of Traditional Chinese Medicine(TCM) between April 1, 2012 and January 31, 2014.All of patients in two groups were treated with standard hormone reduction method. The control group was given orally Bupi Yichang pills, 6 g/time, 3 times/day, and the experimental group was given orally Jianpi Qingchang recipe, 300 mL water decoction, 1 dose/d, 2 times/d. All of the patients received continuous treatment for 3 months. After treatment, disease activity index, mucosal healing evaluation, curative effect changes of TCM syndromes and changes of inflammatory factors in the two groups were observed. Result::Compared with before treatment, the two groups of Mayo scores after treatment were significantly reduced (P<0.01), and the experimental group was reduced more significantly than the control group (P<0.01). After treatment, 66.67%of patients in experimental group were in remission, and 13.33%of patients in control group were in remission, with statistically significant differences between two groups (P<0.01). After treatment, the healing rate of the control group was 46.67%, while that of the experimental group was 70.0%, with statistically significant differences (P<0.01). After treatment, the effective rate of TCM syndromes in control group was 80.0%, while that in experimental group was 96.67%, with statistically significant differences (P<0.01). Compared with control group before treatment, the levels of IL-1 in both groups were decreased (P<0.05), while the levels of IL-6 and IL-10 were increased (P<0.05). Compared with control group after treatment, the changes in experimental group were significantly better than those in control group (P<0.05). Conclusion::Jianpi Qingchang decoction can reduce the index of disease activity in patients with hormone-dependent ulcerative colitis due to spleen deficiency and dampness-heat, promote mucosal healing and improve the curative effect of TCM symptoms, and thus is worthy of clinical promotion.