ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals ; Mice ; Humans ; Ependymoglial Cells/metabolism* ; Hedgehog Proteins/metabolism* ; Ferrets/metabolism* ; Cerebral Cortex ; Neurogenesis ; Mammals/metabolism* ; Neuroglia/metabolism* ; Bone Morphogenetic Protein 7/metabolism*

Objective:To compare the perioperative conditions of open pancreaticoduodenectomy (OPD), laparoscopic pancreaticoduodenectomy (LPD) and LPD conversion OPD, and analyze the short-term prognosis and risk factors for LPD conversion OPD.Methods:The clinical data of 167 patients undergoing pancreaticoduodenectomy (PD) in the Beijing Friendship Hospital, Capital Medical University from February 2020 to March 2023 were retrospectively analyzed. Of 167 patients, 63 patients underwent OPD surgery (OPD group), 91 patients underwent LPD surgery (LPD group), and 13 patients were converted to OPD during LPD surgery (LPD conversion OPD group). The measurement data with non-normal distribution were expressed as median (interquartile range) [ M( Q1, Q3)], and comparison between groups was analyzed using the Kruskal-Wallis H test. The count data were expressed as the number of cases and percentage, and the Chi-square test was used for ordered categorical variable, Kruskal-Wallis H test was used for un-ordered categorical variable. The risk factors of LPD conversion OPD were analyzed by multivariate Logistic regression. Results:The intraoperative blood loss [600(350, 1 000) mL], bilio-intestinal drainage stay time [10(8, 15) d] and bilio-intestinal drainage volume [995(505, 1 502) mL] in the LPD conversion OPD group were significantly higher than those in the LPD group [200(100, 300) mL, 7(6, 6) 10) d, 450(175, 874) mL], the differences were statistically significant ( P<0.05). The operation time of the LPD conversion OPD group [335(293, 385) d] was significantly longer than that of the OPD group [230 (195, 290)d], and the difference was statistically significant ( P<0.05). Multivariate Logistic regression analysis revealed that preoperative complications of chronic pancreatitis ( OR=19.714) and maximum diameter of the lesion ( OR=5.583) has a significant impact on the LPD conversion OPD ( P<0.05). Conclusions:Patients who plan to undergo PD should prefer LPD if the technology and physical condition permit. Preoperative complication of chronic pancreatitis, maximum diameter of lesion > 3.5 cm are the risk factors for LPD conversion OPD, which may significantly increase intraoperative blood loss, prolong the indwelling time of biliary drainage tube, and increase the drainage volume of biliary drainage tube. Therefore, the surgical method should be carefully selected.

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs' roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.
Nucleosomes ; Histones/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Lysine/metabolism* ; Methyltransferases/metabolism* ; Methylation

ObjectiveTo investigate the changes of endogenous metabolites in serum of ovariectomized rats and the effect of Erxiantang on them based on liquid chromatography-mass spectrometry（LC-MS）. MethodTwenty-four healthy female SD rats were randomly divided into sham-operated group， model group and Erxiantang group（7.5 g·kg^-1）， with 8 rats in each group. Bilateral ovarian tissues were excised in the model and Erxiantang groups， and small pieces of adipose tissues were excised in the abdominal cavity of the sham-operated group bilaterally， and gastric administration was started 2 weeks after surgery， and equal volumes of distilled water were gavaged in the sham-operated and model groups. After 12 weeks of administration， blood was collected from abdominal aorta， and non-targeted metabonomics was performed on rat serum by LC-MS， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to screen differential metabolites. Metabolic pathway analysis was performed based on Kyoto Encyclopedia of Genes and Genomes（KEGG）， and the levels of key enzymes of metabolic pathways were verified by enzyme-linked immunosorbent assay（ELISA）. ResultThe results of metabonomics showed that 82 differential metabolites between the model group and the sham-operated group were glycerophospholipids， fatty acyls， steroids and steroid derivatives， of which the most significant difference was glycerophospholipids. At the same time， Erxiantang could call back 65 out of 82 differential metabolites， of which 11 were statistically significant， mainly phosphatidylcholine（PC） and lysophosphatidylcholine（LysoPC） in glycerophospholipids， followed by corticosterone and 11-deoxycortisol in steroids and steroid derivatives. Metabolic pathway analysis showed that the pathways of glycerophospholipid metabolism and steroid hormone biosynthesis in model group were changed， and were recovered after the administration of Erxiantang. ELISA results showed that compared with the sham-operated group， serum levels of cholinephosphate cytidylytransferase（CCT）， secretory phospholipase A2（sPLA2） and lysophosphatidylcholine acyltransferase（LPCAT）， which were the key metabolic enzymes of glycerophospholipid metabolite PC and LysoPC， were significantly decreased in the model group（P<0.05， P<0.01）， and choline phosphotransferase 1（CPT1） levels decreased but the difference was not statistically significant， compared with the model group， the levels of CCT， sPLA2 and CPT1 were significantly increased in Erxiantang group（P<0.01）. In addition， compared with the sham-operated group， the levels of cholesterol（TC）， triglyceride（TG） and low density lipoprotein cholesterol（LDL-C） were significantly increased in the model group（P<0.01）， the high density lipoprotein cholesterol（HDL-C） level was decreased（P<0.05）， compared with the model group， the levels of TC， TG and LDL-C were significantly decreased and the level of HDL-C was significantly increased in Erxiantang group（P<0.01）. ConclusionEndogenous metabolites and related metabolic pathways in ovariectomized rats were altered， and Erxiantang can reverse some of the different metabolites and related pathways， such as regulating glycerophospholipid metabolism by regulating metabolic enzymes CCT， sPLA2 and CPT1 to increase the levels of PC and LysoPC， and then improve the pathological changes such as lipid metabolism disorder in ovariectomized rats.

Objective:To statistically analyze SCI paper output and research hotspots of Chinese stomatology research institutes from 2011 to 2020.Methods:The papers of Chinese stomatology research institutions in the Web of Science database were searched and analyzed by bibliometric methods in various dimensions including publication time, institutional and journal distribution, international (regional) cooperation, and research hotspots.Results:The number and quality of publications in Chinese dental research institutions have increased significantly in the past decade, and the top four institutions in terms of publication number were Sichuan University, Peking University, Shanghai Jiaotong University, and Air Force Military Medical University. The distribution of the journals to which the articles belong was relatively scattered, and the research hotspots mainly focused on squamous cell carcinoma, periodontitis, bone regeneration, and materials science.Conclusions:The output of SCI papers and the number of high-quality papers in Chinese stomatology research institutions increased year by year during 2011-2020, and the scientific research strength continued to increase.

Objective:To explore the influence of Internet diversified rehabilitation medicine education on self-efficacy and quality of life in newly diagnosed breast cancer patients.Methods:A prospective study was performed in 130 newly diagnosed breast cancer patients admitted to Beijing Friendship Hospital, Capital Medical University from February 2020 to February 2021. According to the method of randomly number table, these patients were divided into control group and intervention group, 65 cases in each group.The control group was treated with routine treatment scheme, and the intervention group added the intervention of Internet diversified education of rehabilitation medicine on the basis of routine treatment scheme. Compared the general data of the two groups, the General Self-Efficacy Scale (GSES) and the cancer patients′ Quality of Life Questionnaire-Core 30 (QLQ-C30) were used to compare the self-efficacy levels of the two groups before operation, 4 months and 8 months after operation, evaluate the quality of life. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; Chi-square test was used for comparison of enumeration data between groups. Results:Before operation, there was no significant difference in general data, GSES score and QLQ-C30 score between the two groups ( P> 0.05). Four months after operation, GSES scores [(27.39±4.68) score vs (25.91±3.18)score], somatic function [(65.50±4.34) score vs (63.07±5.42) score], cognitive function [(67.63±10.32) score vs (63.29 ± 11.36) score], role function [(50.82±10.80) score vs (45.59±13.94) score], and total quality of life [(63.47 ± 6.98) score vs (59.26±7.98)score] were compared between the intervention group and the control group, the difference was statistically significant ( P< 0.05). There was no significant difference in the scores of emotional function [(57.60±11.72) score vs (55.53±10.61) score] and social function [(49.86±12.11) score vs (46.13±10.25) score] ( P> 0.05). Eight months after operation, the GSES score [(28.82±3.31) score vs (26.73 ± 3.06) score] of patients in the intervention group and the control group, and the scores of functional areas and overall quality of life in QLQ-C30 score were significantly different ( P< 0.01). Conclusion:the Internet diversified rehabilitation medicine education has a significant effect on improving the self-efficacy of new breast cancer patients, and can improve the quality of life of patients.

Objective： ：To study the regulatory effect of mogrol (MO) on lipid metabolism of hepatic cancer cells and its molecular mechanism. Methods: Oleic acid (OA) was used to induce fat accumulation in hepatocellular carcinoma HepG2 cells and to establish a steatosis cell model. CCK-8 method was used to detect the cytotoxicity of MO to HepG2 cells, and an experimental working concentration without obvious cytotoxicity of MO was chosen. After being treated with different concentrations of MO, lipid accumulation in the cells was observed by oil red O staining, and the contents of triglyceride (TG) and cholesterol (TC) in the cells were measured. Key genes involving in lipid metabolism were screened out by high-throughput transcriptome sequencing qPCR was used to detect the mRNA expressions of ,SREBP-1c and FASN, while Western Blot was used to detect the protein expressions of p-AMPKα, SREBP-1c and FASN in cells of model group and treatment group. Results: After OA induction, a large amount of lipids accumulated in HepG2 cells, the contents of TG and TC increased significantly. Three key genes (SREBP-1c, FASN and p-AMPK α) involving in lipid metabolism of hepatic cancer cells were screened out. After OA induction, the mRNA expressions of SREBP-1c and FASN increased, the protein expression of p-AMPK α decreased while the protein expressions of SREBP-1c, FASN and other proteins increased significantly. After intervention with working concentration of MO, intracellular lipid accumulation, contents of TG and TC, mRNA expressions of SREBP-1c, FASN and protein expressions of SREBP-1c, FASN decreased significantly, while the expression of p-AMPKα increased. Conclusion: Mogrol can inhibit the synthesis of fatty acids by activating the expression level of AMPK signaling pathway related factors SREBP-1c and FASN, so as to play the role of regulating lipid metabolism.

Objective To investigate the clinical features of elderly patients with stage 3-4 chronic kidney disease ( CKD ) and to analyze the risk factors of the kidney function progression. Methods This was a cross-sectional study. The clinic data of elderly patients (≥60 years) with stable clinical manifestation in Beijing Hospital from January ,2014 to December ,2015 was collected.Based upon the eGFR derived from Cockcroft-Gault (CG) equation ,all patients were divided into groups of CKD 3a group ,CKD 3b group and CKD 4 group ,respectively. Moreover ,patients were separated into the old group (＜ 80 years) and the very old group (≥80 years) based on the age. The demographic features ,primary diseases history ,body mass index (BMI) ,blood routine ,urine routine , blood biochemistry ,Cystatin C and iPTH were recorded.Logistic regression analysis of kidney function progression was also conducted. Results One-hundred and eighty-three cases were enrolled with a mean age of(80 ± 9)years.Along with the descent of kidney function ,the age ,levels of proteinuria and iPTH gradually ascended (F＝ 12.352 ,5.910 ,5.910 ;P＝ 0.000 ,0.003 ,0.003 ,respectively) and the BMI and serum albumin gradually descended (F＝9.758 ,11.088 ;P＝0.000 ,0.000 ,respectively).In addition ,compared to the old group ,very old group was associated with decreased level of eGFR [(37.1 ± 9.9) ml·min－1·1.73 m －2vs. (44.0 ± 12.0) ml·min－1·1.73 m －2,t＝ －4.280 ,P＝0.000] and increasedlevelofCystatinC[(1.71±0.84)mg/L vs. (1.40±0.69)mg/L ,t＝3.484 ,P＝0.001].The Logistic regression analysis indicated that the proteinuria was an independent risk factor for the progression of kidney function ( OR ＝3.856 ,P＝0.004). Conclusions As the gradually descended of the eGFR level in elderly patients with stage 3-4 CKD ,age ,proteinuria and iPTH gradually ascended ,BMI and serum albumin descended ,respectively. The level of eGFR decreased and CystatinC increased significantly with the increasing age. Proteinuria was an independent risk factor for progression of the kidney function.

Objective To study CT-guided localization of additional pulmonary nodules with microcoils prior to video-assisted thoracoscopic surgery (VATS) resection in patients with suspected lung cancer.Methods Eleven patients suspected lung cancer underwent preoperative microcoils localization towards additional small pulmonary nodules.The head of microcoil was pinpointed adjacent to the target nodule while its end tail remained above the visceral pleura.VATS were performed within 24 hours, and comprehensive assessments were conducted according to surgical and pathological outcomes of primary and additional lesions, and suitable surgical processes were followed.Results All 11 localizing pulmonary nodules (4-15 mm in diameter) were successfully removed after VATS, 9 microcoils'' end tails of which were placed above visceral pleural surface.There were no serious complications related with localizing procedure.Other 16 lesions including 11 primary ones were resected.The surgical and pathological outcomes for lung lesions were utterly assessed.Conclusion Microcoil preoperative localization provides helpful orientation for complete resection and assessment of multiple pulmonary lesions in patients with suspected lung cancer.