Colorectal cancer is a common and malignant tumor in the digestive tract. Invasion and metastasis of cancer cells are key factors leading to the high mortality rate and postoperative recurrence of colorectal cancer. Chemotherapy is the main treatment method for preventing recurrence of this disease. However， there are many toxic side effects in clinical application， which seriously hinder the treatment process. Therefore， it is imperative to search for efficient and low-toxicity drugs. Traditional Chinese medicine （TCM） has a long history of treating colorectal cancer and offers advantages such as safety， effectiveness， multiple targets， multiple pathways and minimal toxic side effects， which have made it increasingly popular worldwide. According to TCM， the pathogenesis of colorectal cancer is rooted in both deficiency and excess. TCM formulas mainly focus on tonifying the body to address the invasion and metastasis of colorectal cancer， such as Jianpi compound， Jianpi Xiaoai decoction， and Bushen Jiedu Sanjie decoction. TCM monomers， such as emodin， berberine， and tanshinone， mainly focus on clearing heat and removing toxin， circulating blood and transforming stasis， and resolving swelling and dispersing nodules. Signaling pathways play a crucial role for analyzing invasion and metastasis， and research has shown that pathways such as Wnt/β-catenin， phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt）， Janus kinase 2/signal transduction and transcription activating factor 3 （JAK2/STAT3）， nuclear factors-κB （NF-κB）， vascular endothelial growth factor （VEGF） play important roles in the invasion and metastasis of colorectal cancer. The invasion and metastasis of colorectal cancer can be inhibited via regulating the key proteins and related factors in these pathways. In this review， we searched various literature databases， such as PubMed， China National Knowledge Infrastructure （CNKI）， and VIP， using keywords such as "colorectal cancer"， "signaling pathway"， "invasion and metastasis"， and "traditional Chinese medicine"， to summarize and analyze the relevant pathways of TCM compounds and monomers against invasion and metastasis of colorectal cancer published in the past five years. The review aims to provide new insights and references for in-depth research on the therapy for invasion and metastasis of colorectal cancer and new drug development.

ObjectiveTo investigate the potential mechanism of Shenqi Yiliu Formula （参芪抑瘤方） in treating precancerous lesions of gastric cancer （PLGC） by the Wnt/β-catenin signaling pathway. MethodsThe CCK-8 assay was used to determine the optimal intervention time for Shenqi Yiliu Formula drug-containing serum and the concentration of the Wnt/β-catenin pathway inhibitor XAV939 depends on the survival rate of AGS gastric cancer cell line. AGS cells were divided into the gastric cancer cell group （15% blank serum）， inhibitor group （selected concentration of XAV939）， high-dose Shenqi Yiliu Formula group （12% Shenqi Yiliu Formula drug-containing serum + 3% blank serum）， medium-dose Shenqi Yiliu Formula group （6% Shenqi Yiliu Formula drug-containing serum + 9% blank serum）， and low-dose Shenqi Yiliu Formula group （3% Shenqi Yiliu Formula drug-containing serum + 12% blank serum）. Each group was tested in triplicate. After culturing for 24 and 48 hours， cell migration and invasion were assessed by scratch assays； after a selected intervention period （48 hours）， cell cycle distribution was analyzed using flow cytometry， Ki67 protein levels were detected by immunofluorescence， the protein levels of Wnt， β-catenin， GSK-3β， and intranuclear T-cell specific factor（TCF） were measured by the protein immunoblotting assay， and the mRNA expressions of these above factors were determined by quantitative real-time PCR. ResultsThe optimal intervention time for Shenqi Yiliu Formula drug-containing serum was determined to be 48 hours， and the effective concentration of XAV939 was 20 μmol/L. Compared with the gastric cancer cell group， Shenqi Yiliu Formula at all doses reduced the cell migration rate at 24 and 48 hours （P＜0.05）， except for the low-dose group at 24 hours. Compared to the low-dose group at corresponding time points， high- and medium-dose Shenqi Yiliu Formula groups showed significantly reduced migration rates， particularly the high-dose group at 48 hours （P＜0.05）. Compared with the gastric cancer cell group， the high-dose Shenqi Yiliu Formula and inhibitor groups exhibited reduced protein and mRNA levels of Wnt， β-catenin， and TCF， along with reduced Ki67 protein levels and a decreased proportion of cells in the S and G2 phases of the cell cycle， but GSK-3β protein levels， GSK-3β mRNA expression， and the proportion of cells in the G1 phase increased （P＜0.05）. Compared to the inhibitor group， the high-dose Shenqi Yiliu Formula group showed a decreased proportion of G1-phase cells and an increased proportion of G2-phase cells （P＜0.05）， although differences in Wnt and β-catenin protein levels and mRNA expressions were not statistically significant （P＞0.05）. ConclusionShenqi Yiliu Formula drug-containing serum inhibits the migration and invasion of gastric cancer AGS cells and block the cell cycle at G1 phase， and its underlying mechanism may be related to the regulation of the Wnt/β-catenin signaling pathway.

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

As one of the core pathogenesis during treatment with traditional Chinese medicine，liver heat runs through different stages of liver disease. The interpretation of its meaning in different medicine categories（traditional Chinese medicine，Tibetan medicine，Mongolian medicine，Uygur medicine，Dai medicine，Yao medicine，etc.） is not unified， and the phenomena of the same name with different meanings，confusion， and misappropriation emerge. This seriously restricts the inheritance，innovation， and clinical application of traditional Chinese medicine and ethnomedicine. By tracing and analyzing liver heat， it is found that liver heat in traditional Chinese medicine is caused by disordered rest and diet， as well as internal injury due to emotional disorder， which leads to liver dysfunction， Qi stagnation， and heat turning to fire in the liver meridian. The liver heat in Tibetan medicine is caused by the accumulated heat of the liver nature and the evil heat in the liver， which stimulates the toxin of Chiba fever. The liver heat in Mongolian medicine derives from the abnormal diet and rest， making excessive Sheila accumulate in the liver and causing disease. The above etiologies are all related to diet， rest，exogenous evil，emotion，and so on， and the pathogenesis is related to the imbalance of Qi and the metabolic disorder of organs. The clinical symptoms are pain in the liver region，yellow eyes， bitter mouth， fever，digestion，and loss of appetite. The principle of treatment and compatibility of prescription are heat-based， with auxiliary detoxification. Other ethnomedicine， such as Uygur medicine， Dai medicine， Yao Medicine，Miao medicine， and She medicine do not have a clear discussion on liver heat，and their etiology， pathogenesis， treatment，and prescription are not systematic，mostly based on a single drug or proven prescriptions.Through the systematic tracing，mining，induction，analysis， and arrangement of the liver heat based on existing literature information database in China，this paper regarded syndrome as the outline and disease as the goal，clarified the similarities and differences of the pathogenesis of liver heat in traditional Chinese medicine，and determined the relationship between liver heat and liver disease and the status quo of syndrome and treatment.This review provides evidence and reference for clinical prevention and treatment，as well as drug development for liver disease.

The chemical constituents in dried roots of Atractylodes macrocephala were investigated in this study. Through utilizing normal-phase silica gel and ODS column chromatography, TLC, and semi-preparative HPLC, 4 new sesquiterpenoids were purified from the ethyl acetate extract of A. macrocephala. By various spectroscopic techniques, such as 1D and 2D NMR, HR-ESI-MS, IR, UV, and CD, their structures were identified as atractylmacron A (1), 9β-hydroxyasterolide (2), atractylenolide H (3), atractylenolide J (4). Compound 1 possesses a rare 6/7 bicyclic skeleton.

BACKGROUND:Stem cell transplantation is a novel therapy for myocardial infarction,but the extremely hostile microenvironment in the infarct area results in low survival rate of stem cells and little long-term effect.Exercise preconditioning is a way to induce endogenous protective effects through exercise,which can be used as a new strategy for prevention and treatment of cardiac rehabilitation. OBJECTIVE:To evaluate whether exercise preconditioning potentiates the cardioprotective effects of adipose-derived stem cell transplantation following myocardial infarction in rats and to explore the mechanism of angiogenesis. METHODS:Six-week-old male SD rats were randomly divided into control group,modeling group,stem cell group,and stem cell plus exercise group.Acute myocardial infarction model was made by coronary artery occlusion,and sham operation was performed in control group.The stem cell plus exercise group underwent aerobic exercise for 8 weeks before modeling,and adipose-derived stem cell transplantation was performed 30 minutes after modeling.The stem cell group performed only adipose-derived stem cell transplantation.One and seven days after stem cell transplantation,the expression levels of myocardial total Akt(t-Akt),phosphorylated Akt(p-Akt),vascular endothelial growth factor(VEGF),total endothelial nitric oxide synthase(t-eNOS),and phosphorylated endothelial nitric oxide synthase(p-eNOS)protein were measured by western blotting,and the ratios of p-Akt/t-Akt and p-eNOS/t-eNOS were calculated.At 4 weeks after stem cell transplantation,the heart structure and function as well as myocardial blood flow were detected by color Doppler ultrasound diagnostic system.Myocardial infarction area was measured by TTC staining.Myocardial interstitial collagen deposition was examined by Masson staining.Myocardial capillary density was detected by immunofluorescence staining,and myocardial apoptosis was measured by TUNEL staining. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:Compared with control group,left ventricular shortening fraction,left ventricular ejection fraction,myocardial capillary density,and myocardial blood flow decreased(P<0.05),myocardial infarction area,collagen volume fraction,and apoptosis increased(P<0.05)in the modeling group.Compared with the modeling group,the above indexes(except for left ventricular fractional shortening and left ventricular ejection fraction)in the stem cell group improved(P<0.05).Compared with the stem cell group,the above parameters were further improved in the stem cell plus exercise group(P<0.05).(2)One day after stem cell transplantation:Compared with the control group,the protein expression of t-Akt,p-Akt,VEGF,t-eNOS,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS had no significant changes in the modeling group(P>0.05).Compared with the modeling group,there were no significant changes in the above indexes in the stem cell group(P>0.05),and p-Akt protein expression and the ratio of p-Akt/t-Akt were up-regulated in the stem cell plus exercise group(P<0.05).(3)Seven days after stem cell transplantation:Compared with the control group,the protein expression of p-Akt,VEGF,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were decreased in the modeling group(P<0.05).Compared with the modeling group,there were no significant changes in all parameters in the stem cell group(P>0.05),and the protein expression of p-Akt,VEGF p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were increased in the stem cell plus exercise group(P<0.05).These findings confirm that exercise preconditioning can potentiate the therapeutic effect of adipose-derived stem cells on cardiac remodeling in rats with myocardial infarction,and its mechanism is associated with the promotion of myocardial angiogenesis and blood perfusion.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Background: s/Aims: Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer.However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods: We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results: Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region.There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.