ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

ObjectiveTo explore the potential mechanism of action of the combination of Sanguisorbae Radix-Sophorae Flos （DH） in the treatment of ulcerative colitis （UC） using network pharmacology methods and molecular docking technology. MethodsNetwork pharmacology analysis was utilized to predict the potential targets of DH for the treatment of UC. The therapeutic effects were experimentally validated by inducing a UC model in mice with 3% dextran sulfate sodium （DSS）. The experimental groups were the normal group， the model group， the salazosulfapyridine group （100 mg·kg^-1）， and the low， medium， and high dose groups of DH （1.2， 2.4， and 4.8 g·kg^-1）. The efficacy of the treatment was assessed through the general condition of the mice， histopathological examination， and the expression levels of inflammatory markers in the colon. The effect of DH on angiogenesis was explored by messenger RNA （mRNA） detection of colonic angiogenesis-related mediators， vascular endothelial growth factor （VEGF） immunohistochemistry， microvessel density （MVD） detection， and transmission electron microscopy. The phosphatidylinositol-3-kinase （PI3K）-protein kinase B （Akt） signaling pathway proteins were quantitatively analyzed through Western blot to assess whether the suppression of pathological angiogenesis by DH is associated with this pathway. ResultsNetwork pharmacological analysis yielded 112 potential core therapeutic targets for the treatment of UC with DH， of which the core targets were tumor protein 53 （TP53）， JUN， interleukin （IL）-6， Akt1， and tumor necrosis factor （TNF）. Compared with the normal group， mice in the model group showed significant weight loss， colon shortening， and high DAI score， increased expression of inflammatory factors IL-6， IL-1β， and TNF-α， as well as increased mRNA expression levels of angiogenesis-related mediators VEGF， vascular cell adhesion molecule 1 （VCAM1）， angiotensin 1 （Ang1）， matrix metalloproteinase （MMP）-1， MMP-2， and MMP-9. The positive expression of CD31 and VEGF in colonic tissue increased， and the protein expression of the PI3K/Akt pathway was increased （P<0.05）. The endothelial cells of the colonic mucosa and the colonic vasculature were severely damaged. Compared with the model group， mice in the DH groups had significantly reduced weight loss and colon shortening， lower DAI scores， and a significant decrease in mRNA expression of inflammatory factors and angiogenesis-related mediators. In addition， there was decreased positive expression of CD31 and VEGF in colonic tissue and decreased protein expression of the PI3K/Akt pathway （P<0.05）. ConclusionNetwork pharmacology， molecular docking， and experimental validation are applied to explore the mechanism of action of DH in the treatment of UC， and it is found that DH is able to improve the symptoms of colitis and inhibit the pathological angiogenesis in UC mice. Its action might be related to affecting the PI3K/Akt pathway.

There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

Objective:To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology.Methods:Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9.Results:Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4 +Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8 +Teff cells and CD8 +TRM cells; in eCRSwNP, the expression of CD103 in CD8 +TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions:Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103 +CD8 +TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.

Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.

OBJECTIVE：To improve the quality standard of Taraxaci Herba ，and to evaluate the quality of T. officinale from different origins. METHODS ：Based on the provisions of the 2020 edition of Chinese Pharmacopoeia （part Ⅰ）under the item “Taraxaci Herba ”，the method of content determination was added for the detection of water-soluble extracts （hot extraction method）and alcohol-soluble extracts （hot extraction method ），total flavonoids ，chlorogenic acid ，caffeic acid ，cichoric acid and isochlorogenic acid A. HPLC fingerprint was established by using 42 batches of T. officinale from 8 producing areas as object ，and principal component analysis was performed on the basis of above results. RESULTS ：The contents of alcohol-soluble extracts in 42 batches of T. officinale were 15.30％-30.40％，and those of water-soluble extracts were 27.59％-38.96％. The concentration of total flavonoids（UV spectrophotometry ），chlorogenic acid ，caffeic acid ，cichoric acid and isochlorogenic acid A （HPLC method ）were 0.016-0.096，0.003-0.196，0.004-0.117，0.025-1.578，0.002-0.152 mg/mL，respectively （all R2＞0.999）；RSDs of precision ， stability and repeatability tests were all lower than 2.00％（n＝6）；average sample recovery were 98.97％-103.53％，and RSDs were 1.19％-1.58％. The contents of total flavonoids ，chlorogenic acid ，caffeic acid ，cichoric acid and isochlorogenic acid A were 0.734％ -3.700％ ，0.004％ -0.123％ ，0.006％ - 0.087％ ，0.073％ -1.499％ ，0.005％ -0.109％ respectively in 42 batches of T. officinale. For 42 batches of T. officinale samples in HPLC fingerprint ，RSDs of the relative retention time of the common peak were 0-0.94％，and RSDs of the relative peak area were 0-125.57％. Among them ，the similarity of 39 batches of samples was all higher than 0.900. Results of principal component analysis showed that the quality of T. officinale from Shaanxi province was better，followed by medicinal materials from Hebei province. CONCLUSIONS ：Tentatively，the contents of alcohol-soluble extract，water-soluble extract ，total flavonoids ，chlorogenic acid ，caffeic acid ，cichoric acid and isochlorogenic acid A shall not be less than 17.0％，27.0％，1.383％，0.024％，0.021％，0.450％，0.021％ for Taraxaci Herba. In addition to the low content of caffeic acid in T. officinale from Shaanxi province ，the other indexes were better ；the content of caffeic acid in T. officinale from Hebei province was higher than that from Shaanxi province ，and other indicators were slightly lower than that from Shaanxi province. The quality of comprehensive evaluation of T. officinale from other origins was relatively poor ，and the quality of different batches of medicinal materials from the same origin was unstable.

Neuroendocrine prostate cancer(NEPC) is a prostate cancer subtype with a very high degree of malignancy and a special molecular phenotype.NEPC is not sensitive to endocrine therapy, and there are currently no specific drugs, so there is a lack of effective clinical treatment.New advances in NEPC therapeutic include chemical therapy, targeted drug therapy based on molecular phenotype and other non-targeted drug therapy. This article summarizes the current treatment methods, pharmaceutical, and clinical research results for NEPC, aiming to deepen clinicians' more comprehensive understanding of NEPC patients' treatment strategies.

OBJECTIVE: To propose a method of prediction for fatal gastrointestinal bleeding recurrence in hospital and a method of feature selection via machine learning models. METHODS: 728 digestive tract hemorrhage samples were extracted from the first aid database of PLA General Hospital, and 343 patients among them were diagnosed as fatal gastrointestinal bleeding recurrence in hospital. A total of 64 physiological or laboratory indicators were extracted and screened. Based on the ten-fold cross-validation, Logistic regression, AdaBoost and XGBoost were used for classification prediction and comparison. XGBoost was used to search sequence features, and the key indicators for predicting fatal gastrointestinal bleeding recurrence in hospital were screened out according to the importance of the indicators during training. RESULTS: Logistic regression, AdaBoost and XGBoost all get better F1.5 score under each feature input dimension, among which XGBoost had the best effect and the highest score, which was able to identify as many patients as possible who might have fatal gastrointestinal bleeding recurrence in hospital. Through XGBoost iteration results, the Top 30 indicators with high importance for predicting fatal gastrointestinal bleeding recurrence in hospital were ranked. The F1.5 scores of the first 12 key indicators peaked at iteration (0.893), including hemoglobin (Hb), calcium (CA), red blood cell count (RBC), mean platelet volume (MPV), mean erythrocyte hemoglobin concentration (MCH), systolic blood pressure (SBP), platelet count (PLT), magnesium (MG), lymphocyte (LYM), glucose (GLU, blood gas analysis), glucose (GLU, blood biochemistry) and diastolic blood pressure (DBP). CONCLUSIONS Logistic regression, AdaBoost and XGBoost could achieve the purpose of early warning for predicting fatal gastrointestinal bleeding recurrence in hospital, and XGBoost is the most suitable. The 12 most important indicators were screened out by sequential forward selection.
Gastrointestinal Hemorrhage/mortality* ; Health Status Indicators ; Hospital Mortality ; Humans ; Logistic Models ; Machine Learning ; Recurrence

Objective To analyze the therapeutic effect ofShengji-Yuhong ointment in the treatment of patients with pressure ulcer.Methods 86 patients of pressure ulcer were randomly divided into a control group and an observation group, with 43 cases in each. After debridement, the wound was covered with vaseline gauze in the control group, whileShengji-Yuhong ointment in the treatment group. 10 days constituted 1 course of treatment, and both groups were treated for 3 courses. The blood supply of the whole blood viscosity, plasma viscosity, erythrocyte aggregation index detection; white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were observed in order to observe the control condition of the patients with wound infection.Results The total effective rate was 95.3% (41/43) and 74.4% (32/43) in the observation group and control group respectively, with significant difference between two groups (χ2=5.800,P=0.016). After treatment, the whole blood viscosity (high-shea) (4.06 ± 1.38 mPa?svs. 4.74 ± 1.62 mPa?s,t=2.095), the whole blood viscosity (medium-shea) (3.71 ± 1.22 mPa?svs. 4.34 ± 1.41 mPa?s,t =2.216), blood reduction viscosity (1.13 ± 0.22 mPa?svs.1.44 ± 0.51 mPa?s,t=3.660), the whole blood viscosity (medium-shea) (4.16 ± 0.48 mPa?svs. 4.51 ± 0.89 mPa?s,t=2.270) obviously compared with group before treatment decreased (P<0.05). The patients in the observation group in the whole blood viscosity (medium-shea) (3.71 ± 1.22 mPa?svs. 4.16 ± 0.48 mPa?s,t=2.251), and blood reduction viscosity (1.13 ± 0.22 mPa?svs. 1.32 + 0.31 mPa?s,t=3.278) in the observation group were  obvious better than the control group (P<0.05). After the treatment the WBC, CRP, ESR in the observation group were decreased significantly than the control group (t=5.947, 7.198, 12.064,P<0.01).ConclusionShengji-Yuhong ointment can effectively control the PU infection in the wound, improve wound tissue under the blood circulation, and promote wound healing.

Objective To assess the efficacy of combination of Jiehe pellet and the standardized anti-tuberculosis therapeutic regimen for pulmonary tuberculosis complicating cervical lymph node tuberculosis in the aged. Methods A total of 103 aged patients with pulmonary tuberculosis complicating cervical lymph node tuberculosis were enrolled and randomly allocated to either a standardized anti-tuberculosis therapeutic regimen group (control group with 51 patients) or a standardized anti-tuberculosis therapeutic regimen plus Jiehe pellet group (treatment group with 52 patients). The patients in the control group and the treatment group received the treatment with 2HRZE/4HR and 2HRZE/4HR plus Jiehe pellet for 6 months, respectively. The abscessed lymph nodes were treated by either total excision or incision and drainage after 4 weeks of medicine treatment in both groups. Sputum smear was examined for acid-fast bacilli. The CD8 cells expressing natural killer T cells receptors NKG2A, NKG2D in peripheral blood were detected by flow cytometry. The treatment outcome was measured at the end of treatment. Results The rates of lesion resolution (78.85%vs. 58.82%;χ2=4.439, P<0.05) and cavity closure (62.86% vs. 35.48%;χ2=3.893, P<0.05) in the treatment group were significantly higher than those in the control group. In the end of 2, 4 and 6 months of treatment, cumulative rates of sputum conversion from positive to negative in the treatment group were significantly higher than those in the control group (χ2 were 5.343, 5.067 and 4.118,all P<0.05). The CD8 cells expressing NKG2A after treatment in the treatment group were significantly lower than those before treatment in the treatment group (t=9.510, P<0.01) and after treatment in the control group (t=9.832, P<0.01);the CD8 cells expressing NKG2D after treatment in the treatment group were significantly higher than those before treatment in the treatment group (t=10.622, P<0.01) and after treatment in the control group (t=10.433, P<0.01). The serum levels of IL-6 and TNF-αafter treatment were significantly lower than those before treatment in both groups (t were 17.344 and 21.142 in the treatment group, 10.984 and 12.203 in the control group;all P<0.01 );the serum levels of IL-6 and TNF-α after treatment in the treatment group were significantly lower than those after treatment in the control group (t were 7.832 and 5.478,all P<0.01). The serum IL-10 levels after treatment were significantly higher than those before treatment in both groups (t were 12.454 in the treatment group, 7.934 in the control group; all P<0.01 ); and the serum IL-10 level after treatment in the treatment group was significantly higher than that after treatment in the control group (t=4.720, P<0.01). The effective rate for cervical lymph node tuberculosis in the treatment was significantly higher than that in the control group (88.5%vs. 64.7%;χ2=6.855, P<0.01). Conclusion Combination of Jiehe pellet and the standardized anti-tuberculosis therapeutic regimen may improve immune function, increase the rate of sputum conversion from positive to negative, and facilitate lesion resolution in aged patients with pulmonary tuberculosis complicating cervical lymph node tuberculosis.