Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms. In vivo experiments were conducted using 8-week-old SPF male C57BL/6J mice. The T2DM animal model was established by high-fat and high-sugar diet combined with intraperitoneal injections of streptozotocin (STZ), in compliance with the ethical guidelines set by the Animal Welfare Committee of Beijing University of Chinese Medicine (approval number: BUCM-2022021503-1134). In vitro experiments employed human liver cancer HepG2 cells, which were induced with tunicamycin (TM) to establish the ERS cell model. Transcriptomic sequencing was used to analyze changes in gene expression in the liver samples of T2DM mice following ISL treatment. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to assess the regulatory effects of ISL on key ERS genes. Enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunofluorescence techniques were used to evaluate ISL's effects on ERS-related proteins. Results indicate that ISL significantly downregulates the expression of ERS-related genes, reduces the level of glucose-regulated protein 78 (GRP78), and inhibits the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), thereby alleviating abnormal ERS induced by T2DM. Additionally, ISL increases the protein levels of insulin receptor substrate (IRS) 1 and IRS2 and enhances the phosphorylation of protein kinase B (Akt), thereby improving insulin sensitivity. In conclusion, ISL is able to alleviate T2DM associated symptoms by improving abnormal ERS and enhancing insulin sensitivity.

This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

OBJECTIVE: To assess the effectiveness of bone acupuncture in improving pain and function in degenerative lumbar spinal stenosis (DLSS) and compare it with Jiaji acupuncture. METHODS: From January to December 2023, 80 DLSS patients were treated with acupuncture and divided into bone acupuncture and Jiaji acupuncture groups. Among them, 40 patients in the bone acupuncture group included 15 males and 25 females, with a mean age of (60.60±6.98) years old;anthor 40 patients in the Jiaji acupuncture group included 16 males and 24 females, with a mean age of (61.48±9.55) years old. The Roland Morris disability questionnaire(RMDQ), walking distance, visual analogue scale(VAS), and the MOS item short from health survey(SF-36) of two groups at baseline, 2 weeks, 4 weeks, and 12 weeks post-treatment were compared. RESULTS: Eighty patients were followed up for 3 to 5 months with an average of (3.62±0.59) months. There was no significant differences in general data and the scores before treatment between two groups(P>0.05). The RMDQ scores in both groups decreased significantly at 2, 4 and 12 weeks after treatment compared with before treatment(P<0.05), at each time point after treatment, the decrease was more significant in the bone acupuncture group than in the Jiaji acupuncture group(P<0.05). The VAS of waist and leg in both groups was significantly lower at 2, 4 and 12 weeks after treatment that before treatment(P<0.05). At all time points after treatment, the waist VAS in the bone acupuncture group was reduced more significant than in the Jiaji acupuncture group(P<0.05);there was no significant difference in leg VAS at 2 and 12 weeks after treatment between two groups(P>0.05), the improvement was more significant in the bone acupuncture group in the 4 weeks after treatment than in the Jiaji acupuncture group. The SF-36 scores in both groups were significantly higher at 2, 4, and 12 weeks after treatment than before treatment(P<0.05);the SF-36 score raised more significant in the bone acupuncture group than in the Jiaji acupunture group(P<0.05). No significant difference in the walking distance between two groups at 2 weeks after treatment(P>0.05);the walking distance in the bone acupuncture group was significantly higher than that in the Jiaji acupuncture group at 4 and 12 weeks after treatment(P<0.05). CONCLUSION Bone-penetrating acupuncture moderately improves functional impairment, pain, and quality of life in patients with DLSS, showing better efficacy than Jiaji acupuncture.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; Spinal Stenosis/physiopathology* ; Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management

BACKGROUND: Blood glucose and serum albumin have been associated with cardiovascular disease prognosis, but the impact of admission-blood-glucose-to-albumin ratio (AAR) on adverse outcomes in critical ill coronary artery disease (CAD) patients was not investigated. METHODS: Patients diagnosed with CAD were non-consecutively selected from the MIMIC-IV database and categorized into quartiles based on their AAR. The primary outcome was 1-year mortality, and secondary endpoints were in-hospital mortality, acute kidney injury (AKI), and renal replacement therapy (RRT). A restricted cubic splines model and Cox proportional hazard models assessed the association between AAR and adverse outcomes in CAD patients. Kaplan-Meier survival analysis determined differences in endpoints across subgroups. RESULTS: A total of 8360 patients were included. There were 726 patients (8.7%) died in the hospital and 1944 patients (23%) died at 1 year. The incidence of AKI and RRT was 63% and 4.3%, respectively. High AAR was markedly associated with in-hospital mortality (HR = 1.587, P = 0.003), 1-year mortality (HR = 1.502, P < 0.001), AKI incidence (HR = 1.579, P < 0.001), and RRT (HR = 1.640, P < 0.016) in CAD patients in the completely adjusted Cox proportional hazard model. Kaplan-Meier survival analysis noted substantial differences in all endpoints based on AAR quartiles. Stratified analysis and interaction test demonstrated stable correlations between AAR and outcomes. CONCLUSIONS The results highlight that AAR may be a potential indicator for assessing in-hospital mortality, 1-year mortality, and adverse renal prognosis in critical CAD patients.

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Objective To investigate the value of the novel lymphatic contrast-enhanced ultrasound(LCEUS)and conventional venous contrast-enhanced ultrasound(VCEUS)in the differential diagnosis of benign and malignant cervical lymph nodes in patients with thyroid cancer. Methods Patients with suspected thyroid cancer underwent conventional ultrasound,VCEUS,and LCEUS examinations of cervical lymph nodes before biopsy.The diagnostic abilities of conventional ultrasound,VCEUS,and LCEUS were compared with pathological results as the golden standard. Results Forty-four patients with 52 lymph nodes were included in the final data.Thirty-eight metastatic lymph nodes were confirmed by pathological results,and 14 were benign.The diagnostic sensitivity,specificity,and accuracy were 97.37%,71.43%,and 90.38% for LCEUS,92.11%,35.71%,and 76.92% for VCEUS,and 94.74%,21.43%,and 75.00% for conventional ultrasound,respectively.The area under the curve of LCEUS analyzed by the receiver operating characteristic curve was greater than that of VCEUS(P=0.020)and conventional ultrasound(P<0.001). Conclusion LCEUS could significantly improve the differential diagnosis of cervical lymph node metastasis in the patients with thyroid cancer,providing a basis for precise clinical treatment.
Humans ; Thyroid Neoplasms/diagnostic imaging* ; Lymphatic Metastasis/diagnostic imaging* ; Diagnosis, Differential ; Female ; Male ; Middle Aged ; Ultrasonography ; Adult ; Lymph Nodes/pathology* ; Contrast Media ; Neck ; Aged ; Young Adult ; Adolescent ; Sensitivity and Specificity

This paper explores the impacts of accelerated rehabilitation protocols following anterior cruciate ligament reconstruction(ACLR)on bone tunnel enlargement(BTE).While accelerated rehabilitation can shorten the recovery time and improve the knee function,it may increase the risk of BTE.In the early rehabilitation phase after ACLR,excessive early weight-bearing and rapid progression of knee flexion angles should be avoided,along with the proper use of braces.Continuous passive motion is not recommended in the early phase post-ACLR to prevent potential effects on BTE.Further research is needed to investigate the mechanisms of BTE and develop more effective rehabilitation strategies.This will help to select appropriate rehabilitation protocols for patients and balance functional recovery with the risk of BTE,thereby reducing the revision rate and improving postoperative outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/rehabilitation*

Based on the principle of'treating disease and seeking the root cause',Professor FU Wen-Bin proposed'treating radiation encephalopathy(REP)from yang',pointing out that the main pathogenesis of REP is yang qi deficiency,brain spirit dystrophy,phlegm and blood stasis blocking orifices.Using'supplementing yang and unblocking yang simultaneously','treating spirit from heart and gallbladder',combined with the method of regulating spirit and unblocking orifices at acupoints of governor vessol and conception vessel,and using the integrated acupuncture mode of'firstly applying needling,secondly using moxibustion,thirdly focusing on consolidation'to play the role of supporting yang and treating spirit can effectively relieve symptoms and delay the development of the disease.

Objective To determine the acetylation level of nucleophosmin(NPM)in female breast cancer and to discuss its function through mutation of modified lysine sites.To construct positive and negative NPM mutants on its acetylated lysine sites and to express them in breast cancer cells.Methods Acetylation level and acetylated lysine sites of NPM in three breast cancer tissues and para-carcinoma tissues were detected by acetylome technology;NPM mutants were constructed by site-directed mutagenesis PCR,specific PCR products were digested by DpnI and transformed into Escherichia coli(E.coli)to obtain specific plasmids for mutants;The accuracy of mutants were verified by double restriction enzyme digestion and sequencing;The mutants were expressed in BT-549 cells by transient transfection and verified by RT-PCR method.Protein expression and acetylation level of NPM were validated by Western blotting;Function of NPM acetylation was analyzed by proteomic detection and bioinformatic analysis.Results The 27th and 32nd lysine of NPM were highly acetylated in breast cancer tissues,which were 2.76 and 2.22 times higher than those in adjacent normal tissues,respectively;The NPM mutants showed the same molecular weight as that of wild type NPM and contained expected mutation sites;Corresponding NPM mRNA levels of BT-549 cells transfected with NPM mutants were significantly increased.With the increase of wild type NPM expression level,NPM acetylation level increased,while decreased after 27th lysine underwent negative mutation.NPM acetylation can significantly change the expression levels of 101 proteins in BT-549 cells,which are enriched in regulation of cellular macromolecule biosynthesis,DNA-template transcription,RNA biosynthesis and RNA metabolism process.Conclusion NPM is highly acetylated in breast cancer and can play a key role in cellular macromolecule biosynthesis,DNA-templated transcription,RNA biosynthesis and RNA metabolism process.

Apolipoprotein E (apoE) is a critical molecule in lipid metabolism, which also plays important roles in the occurrence and development of several kinds of cancers by regulating processes including cell proliferation, energy metabolism, oxidative stress and innate immune, etc., and shows influence in patients’ response to treatment. Therefore, apoE has become a potential biomarker and treatment target for cancer. Further research of apoE will help us build deep and systematic understanding of etiology of cancer to promote the prevention and to develop new therapeutic strategies for cancer. In this review, we introduced the properties of apoE from the views of biophysics, biochemistry, molecular biology, evolution and epidemiology, in which we demonstrated the similarities and differences among the structures of 3 subtypes of apoE; we also recapitulated the role of apoE in the genesis and development of cancers in main types of malignancies including gastric cancer, colorectal cancer, hepatobiliary cancer, melanoma, pancreatic cancer, etc.; we summarized the relationship between apoE and the hallmarks of cancer, highlighting the position of apoE in immune system and its critical role for understanding the different nature of immunological background of cancers originated from different organs, and discussed its potential value for application as tumor biomarkers and therapeutic targets by demonstrating the structures of its subtypes. We further discussed the possibility of transferring the drug designing strategy of “structure corrector” from neurology to oncology.