ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Renal interstitial fibrosis （RIF） is a common pathological change process from the development of various chronic nephropathies to the end stage， and it is an important histological manifestation of renal function decline. At present， no effective anti-fibrosis drugs have been found in clinical practice. In recent years， with the continuous development of traditional Chinese medicine （TCM） pharmacology， molecular biology， system biology， and network pharmacology， the research on regulating RIF with TCM monomer， single TCM， TCM compound， Chinese patent medicine， and TCM injection is deepening. Among them， Jianpi Yishen recipe， Shendi Bushen capsules， Jianzhong Bushen Xiaozheng decoction， Liuwei Dihuangtang， and Lycium barbarum polysaccharides can regulate transforming growth factor-β/small mother against decapentaplegic （TGF-β₁/Smads）， Wnt/β-catenin， and neurogenic locus notch homolog protein （Notch） signaling pathways. Wulingsan， Zhenwutang， pachymic acid ZA， pachymic acid ZC， and pachymic acid ZD， which mainly induce diuresis， can regulate the Wnt/β-catenin signaling pathway. Hirudin， curcumin， and Fuzheng Huayu recipe， which mainly promote blood circulation， can inhibit inflammation-related pathways such as p-nuclear transcription factor-κB （NF-κB）， Toll-like receptor 4/p-nuclear transcription factor-κB （TLR4/NF-κB）， and Janus kinase 2/signal transducer and activator of transcription 3 （JAK/STAT）， so as to achieve anti-inflammatory and anti-oxidation effects and alleviate the progression of RIF. Shenshuai Xiezhuo decoction， Shenkang injection， and Shenshuai recipe， which are mainly used for invigorating Qi， removing blood stasis， and removing turbidity， can inhibit transdifferentiation of pericytes-myofibroblasts through vascular endothelial growth factor receptor （VEGFR） signaling pathway. At present， there are many studies on the regulation of the RIF signaling pathway by TCM， but there is a lack of a systematic summary. In this study， by combing the signaling pathway of TCM in the treatment of RIF， the effective target of TCM treatment is screened， and its possible mechanism is found， which provides new ideas for clinical treatment and new drug research and development.

Tumorigenesis， invasion， and metastasis occur in the context of a persistent inflammatory microenvironment， and a variety of inflammatory factors can lead to the development of various tumors. Guided by the thought of "preventive treatment of disease" in TCM and the concept of tertiary prevention in modern medicine， it is of great significance to effectively intervene in the inflammatory stage of the disease， interrupt disease progression， prevent the occurrence of malignant tumors， and reverse the process of "inflammation-to-cancer transformation". Sinisan， a commonly used prescription in the Treatise on Febrile Diseases， has been widely applied in the treatment of precancerous lesions of the digestive system， demonstrating considerable advantages. This article reviewed literature from the past 20 years， summarizing the application of Sinisan in precancerous lesions of the digestive system from three aspects： the exploration of its prescription-syndrome relationship， clinical application， and mechanistic study. It is found that basic syndrome indications of Sinisan include harmonizing the Earth element to promote spleen-stomach transportation and transformation， soothing the liver and nourishing the Wood element to restore the smooth flow of Qi， and regulating Yin and Yang to relieve stagnation within the system. In clinical application， Sinisan has shown significant efficacy in atrophic gastritis and precancerous conditions such as intestinal metaplasia， gastric ulcer， ulcerative colitis， esophagitis， and pancreatitis. Mechanistic studies have revealed that Sinisan can inhibit inflammatory factors and improve the inflammatory microenvironment， inhibit cell proliferation and regulate apoptosis， exhibit anti-angiogenic and antitumorigenic effects， modulate immune function， and exert antioxidant effects. These mechanisms can be achieved by regulating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， farnesoid X receptor （FXR）/Nrf2， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A （TGR5/cAMP/PKA）， interleukin-4/signal transducer and activator of transcription 6 （IL-4/STAT6）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， RhoA/Rho-associated protein kinase （RhoA/ROCK）， and transforming growth factor-β/Smad proteins （TGF-β/Smads）， confirming Sinisan's role in reversing the inflammation-to-cancer transformation. The current research status of Sinisan in precancerous lesions of the digestive system was thoroughly examined through the above three aspects， along with the identification of limitations and areas for improvement in current research. The aim is to provide a basis and support for future in-depth research on Sinisan， promote the development of new integrated treatment models combining TCM and Western medicine for precancerous lesions， and aid in the research and development of drugs related to precancerous lesions.

Malignant tumor is a serious and difficult disease threatening human health， which has a high morbidity and mortality rate worldwide. Traditional Chinese medicine has unique advantages in improving the therapeutic effect of malignant tumors and alleviating adverse reactions. Traditional Chinese medicine believes that Qi deficiency and blood stasis are important pathogeneses in the development of malignant tumors， and the method of supplementing Qi and activating blood is an effective strategy for treating malignant tumors. Astragali Radix， sweet in taste and warm in nature， has effects of tonifying Qi and rising Yang， strengthening the exterior and reducing sweat， promoting fluid and nourishing blood. Curcumae Rhizoma， acrid and bitter in taste and warm in nature， has the effects of promoting Qi and breaking blood stasis， eliminating mass， and relieving pain. Astragali Radix-Curcumae Rhizoma， as the classic herb pair of invigorating Qi and activating blood， has a clear effect on inhibiting tumor growth and metastasis. Studies have shown that Astragali Radix-Curcumae Rhizoma contains astragalus polysaccharide， astragaloside， calycosin， formononetin， curcumin， β-elemene， curcumenol， curcumenone， curcumendione， gemacrone， and other anti-tumor active ingredients. It can significantly inhibit the occurrence and development of liver cancer， colorectal cancer， gastric cancer， lung cancer， ovarian cancer， cervical cancer， breast cancer， and other cancers and has the advantages of superposition effect， synergistic complementarity， and increased dissolution compared with single herb and monomer of Chinese traditional herbs and has been widely valued in the field of TCM anti-cancer. Its anti-tumor mechanism includes inhibition of tumor cell proliferation， promotion of tumor cell apoptosis and autophagy， anti-invasion and metastasis， regulation of immune function， and enhancement of anti-tumor drug sensitivity. By combining Chinese and foreign literature， the compatibility effect and anti-tumor mechanism of Astragali Radix-Curcumae Rhizoma were summarized， and then scientific compatibility of these two herbs was expounded， in order to provide a useful reference for clinical application and future research of Astragali Radix-Curcumae Rhizoma.

OBJECTIVE: To develop and validate a predictive model for the risk of bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). METHODS: A literature search was conducted in PubMed, Cochrane Library, and Embase databases from inception to July 2022 to identify studies reporting statistically significant risk factors for CRKP-BSI. Relative risks (RR) were extracted and pooled. Based on factor weights, a risk-scoring model was established. For external validation, hospitalized CRKP-infected patients from January 2016 to January 2022 at Shanghai First People's Hospital were included. Clinical data were used to calculate individual risk scores. The predictive accuracy was assessed using receiver operator characteristic curve (ROC curve). Patients were stratified into low-to-intermediate-risk and high-risk groups based on the optimal cut-off, and CRKP BSI incidence was compared between groups. RESULTS: The literatures related to the risk factors of CRKP-BSI published from database inception to July 2022 was retrieved and screened from PubMed, Cochrane Library, and Embase. Fourteen risk factors were included in the scoring model: cardiovascular disease, severe neutropenia or immunosuppression, intensive care unit (ICU) stay history, prior hospitalization, carbapenem exposure, aminoglycoside exposure, antifungal exposure, endotracheal intubation or tracheostomy, mechanical ventilation, hemodialysis, central venous catheter, indwelling urinary catheter, CRKP colonization, and Klebsiella pneumoniae positivity at non infection sites. The total score ranged from 0 to 173.5 points. In the validation cohort of 230 CRKP-infected patients, 41 developed CRKP BSI. The model yielded an area under the curve (AUC) of 0.783 (95%CI was 0.689-0.876). The optimal cut off was 81.25 points, with sensitivity of 75.6% and specificity of 81.0%. Based on this cut off, 163 patients were categorized as low-to-intermediate risk and 67 patients as high risk. The incidence of CRKP BSI in the high-risk group was significantly higher than in the low-to-intermediate-risk group [64.2% (43/67) vs. 4.9% (8/163); RR = 13.175 (95%CI was 5.920-29.319), P < 0.001]. CONCLUSIONS The model, based on 14 routinely available clinical parameters, demonstrated good performance in predicting CRKP BSI risk and may assist clinicians in early identification of high risk patients.
Humans ; Klebsiella pneumoniae/drug effects* ; Klebsiella Infections/microbiology* ; Carbapenems/pharmacology* ; Risk Factors ; Bacteremia/microbiology* ; ROC Curve ; Carbapenem-Resistant Enterobacteriaceae

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.