OBJECTIVE: To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture. METHODS: Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared. RESULTS: When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS. CONCLUSION For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.
Humans ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Bone Screws ; Bone Plates ; Biomechanical Phenomena ; Finite Element Analysis

OBJECTIVE: To determine the thermic effect of food (TEF) in a Chinese mixed diet in young people. METHODS: During the study, the participants were weighed and examined for body composition every morning. The total energy expenditure (TEE) of the participants was measured by the doubly labeled water method for 7 days, and during this period, basal energy expenditure was measured by indirect calorimetry and physical activity energy expenditure was measured by an accelerometer. The value obtained by subtracting basal energy expenditure and physical activity energy expenditure from TEE was used to calculate TEF. RESULTS: Twenty healthy young students (18-30 years; 10 male) participated in the study. The energy intake of the participants was not significantly different from the Chinese Dietary Reference Intake of energy ( P > 0.05). The percentage of energy from protein, fat and carbohydrate were all in the normal range. The intakes of fruits, milk and dietary fiber of the participants were significantly lower than those in the Chinese Dietary Guidelines ( P < 0.05). There was no significant difference in the body weight of the participants during the experiment ( P > 0.05). When adjusted for body weight, there was no significant difference in either TEE or basal energy expenditure between the male and female participants ( P > 0.05). In addition, there was no significant difference in physical activity energy expenditure and TEF between the male and female participants ( P > 0.05). The percentage of TEF in TEE was 8.73%. CONCLUSION The percentage of TEF in TEE in a Chinese mixed diet in young people was significantly lower than 10% ( P < 0.001). A value of 10% is usually considered to be the TEF in mixed diets as a percentage of TEE.
Adolescent ; Female ; Humans ; Male ; Body Composition ; Body Weight ; Diet ; East Asian People ; Energy Intake ; Energy Metabolism ; Exercise ; Young Adult ; Adult

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.
Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Nomograms ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms/surgery*

ObjectiveTo observe the effects of Hedysarum polysaccharides（HPS）on the signaling pathways of B-cell lymphoma 2 （Bcl-2）， cysteinyl aspartate-specific protease 3 （Caspase-3）， and Bcl-2-associated X protein （Bax） in Schwann cells（SCs）cultured in high glucose，and explore the possible mechanism of HPS against diabetic peripheral neuropathy（DPN）. MethodFour SD suckling mice aged 5-7 days were randomly divided into a normal group，a high-glucose group，an HPS + high-glucose group，and an α-lipoic acid（α-LA）+ high-glucose group. SCs were extracted from the sciatic nerve and cultured in a 37 ℃，5% CO₂ incubator. After the cells reached 80% confluence，Cell Counting Kit-8（CCK-8）was used to screen the experimental concentrations suitable for high glucose，HPS， and α-LA interventions. Western blot and Real-time polymerase chain reaction （Real-time PCR）were used to detect the protein and mRNA expression of Bcl-2，Bax，and Caspase-3. The apoptosis rate of SCs was detected by flow cytometry using Annexin V-fluorescein isothiocyanate （FITC）/propidium iodide （PI）. ResultAs revealed by Western blot and real-time PCR，compared with the normal group，the high-glucose group showed reduced protein and mRNA expression of Bcl-2 and increased protein and mRNA expression of Bax and Caspase-3（P<0.01）. Compared with the high-glucose group，the HPS + high-glucose group and the α-LA + high-glucose group showed increased protein and mRNA expression of Bcl-2 and decreased protein and mRNA expression of Bax and Caspase-3（P<0.01）. As displayed by the results of flow cytometry using Annexin V/PI， compared with the normal group，the high-glucose group showed increased apoptosis rate；compared with the high-glucose group，the HPS + high-glucose group and the α-LA + high-glucose group showed reduced apoptosis rate（P<0.01）. ConclusionHPS can alleviate the apoptotic response of SCs，and its mechanism may be related to the inhibition of the activation of the Bcl-2/Caspase-3 signaling pathway.

Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg^-1·d^-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 μg·kg^-1·d^-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.
Aminobutyrates/pharmacology* ; Animals ; Apelin/metabolism* ; Biphenyl Compounds ; Collagen/metabolism* ; Doxorubicin/pharmacology* ; Fibrosis ; Heart Failure/pathology* ; Male ; Myocytes, Cardiac/pathology* ; RNA, Messenger/metabolism* ; Rats ; Rats, Wistar ; Valsartan/pharmacology* ; Ventricular Function, Left/drug effects* ; Ventricular Remodeling

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

OBJECTIVE: To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities. METHODS: The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis. RESULTS: The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup. CONCLUSION The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups.

The liver plays an important role in the metabolism, degradation, and excretion of thyroid hormones in the normal physiological state; however, when liver injuries occur, there is a significance increase in hypothyroidism, and most patients have no obvious clinical symptoms or signs. The article summarizes the chronic liver diseases caused by various etiologies and the change in thyroid function in different stages of disease and points out that the reduction in the level of thyroid hormone has an important value in predicting the risk, condition, and prognosis of chronic liver diseases. Studies have shown that some patients with chronic liver diseases can improve the condition and prognosis by adjusting thyroid function. In addition, a series of genetic disorders or dysfunctions caused by abnormal thyroid metabolism may become new therapeutic targets for certain chronic liver diseases, which needs to be confirmed by further studies.

Network pharmacology, molecular docking and in vivo experiments were used to explore the pharmacodynamic basis and potential mechanism of Danggui Sini Decoction in the treatment of primary dysmenorrhea(PD). The chemical constituents of Danggui(Angelicae Sinensis Radix), Guizhi(Cinnamomi Ramulus), Tongcao(Tetrapanacis Medulla), Baishao(Paeoniae Radix Alba), Xixin(Asari Radix et Rhizoma), Gancao(Glycyrrhizae Radix et Rhizoma), and Dazao(Jujubae Fructus) from Danggui Sini Decoction were retrieved through TCMSP(Traditional Chinese Medicine Systems Pharmacology Database), and the action targets of Danggui Sini Decoction were collected through DrugBank. "Primary dysmenorrhea" and "dysmenorrhea" were used as the key words to search the corresponding targets in the GeneCards, OMIM and TTD databases, and then the intersection targets of Danggui Sini Decoction and the primary dysmenorrhea targets were taken for reverse screening to obtain the corresponding active ingredients. Cytoscape 3.6.1 software was used to construct a traditional Chinese medicine-compound-target-disease network; STRING database was used to build a protein-protein interaction(PPI) network; Gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted by using DAVID database. The action mechanism of the intersection targets were then predicted, and a histogram chart and bubble chart were drawn for visualization. Then the top five targets in the PPI network were used for docking with the most compounds. In animal experiments, Sprague Dawley(SD) female rats were used to establish a primary dysmenorrhea model by intraperitoneal injection of diethylstilbestrol once a day. A total of 60 SD female rats were randomly divided into 6 groups, namely control group, model group, Danggui Sini Decoction low(1.5 g·kg~(-1)), medium(3.0 g·kg~(-1)), high(6.0 g·kg~(-1)) dose groups, and ibuprofen(20 mg·kg~(-1)) positive control group, with 10 rats in each group. From day 4, except for the control group, rats in the other groups were given intragastric administration of corresponding drugs, and the control group received intragastric administration of normal saline for 7 consecutive days. The number of writhing before and after the administration, the ute-rine contraction inhibition rate and the uterine index after administration were observed, and ELISA assay was used to detect the levels of prostaglandin-endoperoxide synthase 2(PTGS2) and vascular endothelial growth factor A(VEGFA) in the tissues of each group as well as the levels of serum inflammatory factors interleukin 1(IL-1), interleukin 6(IL-6), and tumor necrosis factor-alpha(TNF-α). According to network analysis, 7 Chinese medicines contained 114 active ingredients, 149 targets, and 30 common target genes with PD were obtained. The key targets included VEGFA, IL6, PTGS2, TNF, etc.; GO function enrichment analysis showed a total of 399 terms(P<0.05) were obtained, 353 of which were biological process(BP) terms, 21 were cell composition(CC) terms, and 25 were molecular function(MF) terms. In KEGG pathway enrichment analysis, 14 signaling pathways were obtained, 3 of which were related to inflammation, namely arachidonic acid metabolism, MAPK signaling pathway and NOD-like receptor signaling pathway. The compounds in Danggui Sini Decoction can play a therapeutic role in the treatment of PD by acting on VEGFA, IL-6, PTGS2, TNF and other targets to regulate arachidonic acid and inflammatory signaling pathways.
Animals ; Drugs, Chinese Herbal ; Dysmenorrhea/drug therapy* ; Female ; Humans ; Molecular Docking Simulation ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A

In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)-based liver metabolomics approach was used to explore the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in improving atherosclerosis(AS) of mice with apolipoprotein E gene knockout(ApoE~(-/-)). AS mouse model was induced by high-fat diet. The pathological and biochemical indexes such as the histopathological changes, body weight, liver weight, blood lipid level and inflammatory factors in the liver of mice were determined. The metabolic profiling of mice liver samples was performed with UPLC-Q-TOF-MS. Multiple statistical analysis methods including partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to screen and identify biomarkers. The levels of related enzymes including LCAT, sPLA2, EPT1 and ACER1 were detected. The results showed that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" significantly reduced the areas of aortic plaque and fat vacuoles of liver in AS mice and decreased the accumulation of lipid droplets and liver coefficient. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" also regulated the levels of blood lipid and inflammatory injury in the liver. The metabolites of the control group, the model group and the "Trichosanthis Fructus-Allii Macrostemonis Bulbus" group could be distinguished significantly. Fifteen potential biomarkers related to AS were discovered and preliminarily identified, seven of which could be regulated by "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in a trend of returning to normal. Metabolic pathway analysis screened out two major metabolic pathways. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" obviously regulated the levels of LCAT, sPLA2, EPT1 and ACER1. It was inferred that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" could play a major role in AS treatment by regulating glycerophospholipid and sphingolipid metabolism disorders in the liver, with the mechanism probably relating to the intervention of the expression of LCAT, sPLA2, EPT1 and ACER1.
Animals ; Apolipoproteins E/genetics* ; Atherosclerosis/genetics* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Liver ; Metabolomics ; Mice