Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

ObjectiveTo establish a quality evaluation method for Zhuye Shigao granules（Zhuye Shigaotang） based on fingerprint and determination of index components， and to investigate the therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome. MethodsThe fingerprint of Zhuye Shigao granules was established by high performance liquid chromatography（HPLC）， and the methods for determination of total calcium， orientin， isoorientin， ginsenosides Rg₁， Re and Rb₁ and other 2 index components were established. Fifty ICR mice were randomly divided into the blank group， model group， Zhuye Shigao granules low， medium and high dose groups（9.3， 18.6， 37.2 g·kg^-1·d^-1）， with 10 mice in each group. In addition to the blank group， the model mice with cold-dampness pestilence attacking lung syndrome was prepared by nasal drip of lipopolysaccharide combined with cold-dampness environment. Each administration group was given the corresponding liquid by gavage according to the dose， while the blank group and model group were given the same volume of normal saline by gavage. Then， the body temperature and organ index of mice in each group were measured， hematoxylin-eosin（HE） staining was used to investigate the lung tissue injury of mice in each group， and enzyme-linked immunosorbent assay（ELISA） was used to detect the changes of tumor necrosis factor-α（TNF-α）， interleukin（IL）-lβ， IL-6， IL-10 levels in serum and lung tissue， as well as immunoglobulin（Ig）A and IgM levels in serum. ResultsThe fingerprint similarity of 10 batches of Zhuye Shigao granules was>0.950， and 20 common peaks were calibrated. Seven of them were identified， including peak 11（isoorientin）， peak 12（orientin）， peak 14（apioside liquiritin）， peak 15（liquiritin）， peak 17（apioside isoliquiritin）， peak 19（isoliquiritin） and peak 20（liquiritigenin）. The results of quantitative analysis showed that the content range of each index component in 10 batches of Zhuye Shigao granules was as follows：Total calcium of 9.978-11.294 mg·g^-1， isoorientin of 0.033-0.041 mg·g^-1， orientin of 0.046-0.055 mg·g^-1， ginsenoside Rg₁+ginsenoside Re of 0.748-0.762 mg·g^-1， ginsenoside Rb₁ of 0.151-0.197 mg·g^-1， liquiritin of 1.106-1.366 mg·g^-1， glycyrrhizic acid of 0.904-1.182 mg·g^-1_. Compared with the blank group， the body temperature of mice in the model group was significantly increased， the organ indexes of liver， lung and spleen were significantly decreased， the organ index of thymus was significantly increased， HE staining of lung tissue showed infiltration of inflammatory cells， a small amount of serous exudation was observed in the alveoli， and lung tissue was damaged. After the intervention of Zhuye Shigao granules， the pathological changes were improved compared with the model group. The expression levels of IL-1β， IL-6 and TNF-α were significantly increased， the expression level of IL-10 was significantly decreased in serum and lung tissue. The levels of IgA and IgM in serum were significantly decreased（P<0.01）. Compared with the model group， the body temperature， the organ indexes and immune factor levels in serum and lung tissue of mice in the Zhuye Shigao granules medium and high dose groups were significantly reduced（P<0.05， P<0.01）. ConclusionIn this study， the quality evaluation of Zhuye Shigao granules was carried out based on fingerprint combined with determination of index components， and the fingerprint of four herbs（Lophatheri Herba， Ophiopogonis Radix， Pinelliae Rhizoma and Glycyrrhizae Radix et Rhizoma） in this formula and the determination of 8 index components were established. The therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome may be related to inhibiting inflammatory response and mediating immune regulation.

ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis. MethodsThirty Balb/c mice were randomly grouped as follows （n=6）： normal， model， Kaixuan Jiedu （KXJD， 15.21 g·kg^-1）， Kaixuan （KX， 3.08 g·kg^-1）， and Jiedu （JD， 12.13 g·kg^-1）. Except the normal group， the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod， and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index （PASI） was calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor （VEGF）， platelet-endothelial cell adhesion molecule （CD31）， proliferating cell nuclear antigen （Ki67）， and cytokeratin 10 （CK10） in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23）. The spleen and thymus were photographed and weighed， and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum， liver， and kidney functions and by HE staining of the liver， kidney and spleen. ResultsCompared with that of the normal group， the skin of the model group showed erythema， infiltration， and typical psoriasis-like changes， tortuous dilation of dermal capillaries， hyperkeratosis in epidermal cells， acanthosis， massive lymphocytic infiltration in the dermis， impaired barrier function， increased expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， reduced expression of Claudin-1 and Occludin （P<0.01） in the epidermis， and up-regulated mRNA levels of IL-17A and IL-23 （P<0.01）. In addition， the mice in the model group showed spleen enlargement， thymus atrophy， increased spleen index， and decreased thymus index （P<0.01）. Compared with the model group， KXJD and JD reduced psoriasis-like skin lesions， inhibited the tortuous dilation of dermal capillaries， reduced the expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， increased the expression of claudin-1 （P<0.01）， and down-regulated the mRNA levels of inflammatory factors （P<0.01）. Moreover， the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index， thymus index， and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group. ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis， which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells， tortuous dilation of dermal capillaries， and inflammatory reactions， as well as the protection of the skin barrier. Moreover， KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective， causing no obvious liver and kidney injuries.

ObjectiveTo investigate the efficacy and safety of Kaixuan Jiedu compatibility and the decomposed prescriptions in the treatment of psoriasis. MethodsThirty Balb/c mice were randomly grouped as follows （n=6）： normal， model， Kaixuan Jiedu （KXJD， 15.21 g·kg^-1）， Kaixuan （KX， 3.08 g·kg^-1）， and Jiedu （JD， 12.13 g·kg^-1）. Except the normal group， the rest groups were modeled for psoriasis-like skin lesions by topical application of imiquimod， and samples were collected after 7 days of continuous intervention. Mice were photographed at the lesion site during modeling and before sampling and the psoriasis area and severity index （PASI） was calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the lesions and measure the epidermal thickness. Mice were photographed and observed for the tortuous dilation of dermal capillaries. The expression of vascular endothelial growth factor （VEGF）， platelet-endothelial cell adhesion molecule （CD31）， proliferating cell nuclear antigen （Ki67）， and cytokeratin 10 （CK10） in the epidermal tissue was detected by immunohistochemistry. Immunofluorescence assay was employed to determine the expression of Claudin-1 and Occludin. Real-time PCR was employed to determine the mRNA levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23）. The spleen and thymus were photographed and weighed， and the spleen and thymus indices were calculated. The safety of the treatment was assessed by automatic biochemistry testing of the serum， liver， and kidney functions and by HE staining of the liver， kidney and spleen. ResultsCompared with that of the normal group， the skin of the model group showed erythema， infiltration， and typical psoriasis-like changes， tortuous dilation of dermal capillaries， hyperkeratosis in epidermal cells， acanthosis， massive lymphocytic infiltration in the dermis， impaired barrier function， increased expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， reduced expression of Claudin-1 and Occludin （P<0.01） in the epidermis， and up-regulated mRNA levels of IL-17A and IL-23 （P<0.01）. In addition， the mice in the model group showed spleen enlargement， thymus atrophy， increased spleen index， and decreased thymus index （P<0.01）. Compared with the model group， KXJD and JD reduced psoriasis-like skin lesions， inhibited the tortuous dilation of dermal capillaries， reduced the expression of VEGF， CD31， Ki67， and CK10 （P<0.01）， increased the expression of claudin-1 （P<0.01）， and down-regulated the mRNA levels of inflammatory factors （P<0.01）. Moreover， the KXJD group outperformed the JD group. The JD group showed no significant difference from the model group regarding the spleen index， thymus index， and Occludin expression. The psoriasis indicators in the KX group were not significantly different from those in the model group. ConclusionKXJD and JD can reduce the symptoms of local skin lesions of psoriasis， which is manifested as different inhibition degrees of the proliferation and differentiation of keratin-forming cells， tortuous dilation of dermal capillaries， and inflammatory reactions， as well as the protection of the skin barrier. Moreover， KXJD outperformed JD. KX alone did not significantly reduce psoriasis lesions in mice. KXJD and the decomposed prescriptions are safe and effective， causing no obvious liver and kidney injuries.

BACKGROUND: Over 20 million colonoscopies are performed in China annually. An automatic clinical decision support system (CDSS) with accurate semantic recognition of colonoscopy reports and guideline-based is helpful to relieve the increasing medical burden and standardize the healthcare. In this study, the CDSS was built under a hierarchical-label interpretable classification framework, trained by a state-of-the-art transformer-based model, and validated in a multi-center style. METHODS: We conducted stratified sampling on a previously established dataset containing 302,965 electronic colonoscopy reports with pathology, identified 2041 patients' records representative of overall features, and randomly divided into the training and testing sets (7:3). A total of five main labels and 22 sublabels were applied to annotate each record on a network platform, and the data were trained respectively by three pre-training models on Chinese corpus website, including bidirectional encoder representations from transformers (BERT)-base-Chinese (BC), the BERT-wwm-ext-Chinese (BWEC), and ernie-3.0-base-zh (E3BZ). The performance of trained models was subsequently compared with a randomly initialized model, and the preferred model was selected. Model fine-tuning was applied to further enhance the capacity. The system was validated in five other hospitals with 3177 consecutive colonoscopy cases. RESULTS: The E3BZ pre-trained model exhibited the best performance, with a 90.18% accuracy and a 69.14% Macro-F1 score overall. The model achieved 100% accuracy in identifying cancer cases and 99.16% for normal cases. In external validation, the model exhibited favorable consistency and good performance among five hospitals. CONCLUSIONS The novel CDSS possesses high-level semantic recognition of colonoscopy reports, provides appropriate recommendations, and holds the potential to be a powerful tool for physicians and patients. The hierarchical multi-label strategy and pre-training method should be amendable to manage more medical text in the future.
Humans ; Colonoscopy/methods* ; Deep Learning ; Decision Support Systems, Clinical ; Female ; Male

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*