ObjectiveTo investigate the effect of astragaloside Ⅳ（AS-Ⅳ） on the proliferation of vascular smooth muscle cells（VSMCs） induced by angiotensin Ⅱ（Ang Ⅱ） based on solute carrier family 7 member 11/glutathione peroxidase 4（SLC7A11/GPX4） pathway. MethodsPrimary rat thoracic aortic VSMCs were cultured by tissue explant method， and the cell types were identified by immunofluorescence. Cell counting kit-8（CCK-8） was used to determine the optimal concentration and time of AS-Ⅳ after Ang Ⅱ stimulation. The experiment was divided into blank group， model group， AS-Ⅳ group（40 μmol·L^-1）， Erastin group（0.5 μmol·L^-1）， Erastin+AS-Ⅳ group（0.5 μmol·L^-1+40 μmol·L^-1）. The blank group was cultured in normal medium， the model group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1）， and each administration group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1） and the corresponding doses of drug. CCK-8 and plate clone formation assay were used to detect the proliferation of cells in each group， Prussian blue staining was used to detect cell iron deposition， the content of reactive oxygen species（ROS） in cells was detected by fluorescence probe method， the content of malondialdehyde（MDA） was detected by thiobarbituric acid（TBA） method， and the protein levels of SLC7A11 and GPX4 in each group were detected by Western blot. ResultsPrimary rat thoracic aortic VSMCs were successfully cultured by tissue explant method， and immunofluorescence detection showed that positive expression of α-smooth muscle actin（α-SMA） and negative expression of vimentin in the cells， identifying them as VSMCs. The optimal concentration and time of AS-Ⅳ determined by CCK-8 were 40 μmol·L^-1 and 24 h， respectively. Pharmacodynamic studies showed that compared with the blank group， the cell proliferation in the model group increased， the iron deposition in the cells increased， the contents of ROS and MDA increased， and the expression levels of SLC7A11 and GPX4 proteins decreased（P<0.05， P<0.01）. Compared with the model group， the cell proliferation of the AS-Ⅳ group was inhibited， the iron deposition in the cells was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. While in the Erastin group， the cell proliferation was increased， the iron deposition was increased， ROS and MDA contents were increased， and the expression levels of SLC7A11 and GPX4 proteins were decreased（P<0.05， P<0.01）. Compared with the AS-Ⅳ group， Erastin+AS-Ⅳ group showed increased cell proliferation， increased iron deposition in cells， increased ROS and MDA contents， and decreased expression of SLC7A11 and GPX4 proteins（P<0.05）. Compared with the Erastin group， the cell proliferation in Erastin+AS-Ⅳ group was inhibited， the iron deposition was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. ConclusionAS-Ⅳ can inhibit ferroptosis by regulating the SLC7A11/GPX4 pathway， so as to weaken the proliferation of VSMCs， thus playing a role in the treatment of atherosclerosis.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues. Magnesium has been proved to promote bone healing under normal conditions. Here, we elucidate the mechanism by which Mg²⁺ promotes angiogenesis and osseointegration in diabetic status. We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised, with significantly decreased angiogenesis. We then developed Mg-coating implants with hydrothermal synthesis. These implants successfully improved the vascularization and osseointegration in diabetic status. Mechanically, Mg²⁺ promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells, thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia. Altogether, our data suggested that Mg²⁺ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.
Mice ; Animals ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Magnesium/metabolism* ; Osseointegration ; Diabetes Mellitus, Experimental/metabolism* ; Endothelial Cells/metabolism* ; NF-E2-Related Factor 2/metabolism*

Objective:To investigate the value of digital medical 3D technology versus traditional 2D technology in the diagnosis and treatment of solid abdominal tumors in children. Methods:A total of 80 children with solid abdominal tumors who received surgical treatment guided by digital medical 3D technology at Guigang People's Hospital from January 2018 to January 2022 were included in the observation group. An additional 80 children with solid abdominal tumors who received surgical treatment guided by traditional 2D technology at the same hospital from January 2014 to December 2017 were included in the control group. Clinical efficacy was compared between the two groups.Results:The surgical time, intraoperative blood loss, postoperative exhaust time, postoperative hospital stay in the observation group were (111.8 ± 28.9) minutes, (26.8 ± 25.2) mL, (2.2 ± 1.2) days, (7.5 ± 1.4) days, respectively, which were significantly shorter or less than those in the control group [(193.1 ± 66.0) minutes, (86.2 ± 47.0) mL, (3.7 ± 0.9) days, (12.2 ± 3.5) days, t = 7.00, 6.88, 5.87, 7.53, all P < 0.05]. The complete surgical resection rate in the observation group was significantly higher than that in the control group [92.5% (74/80) vs. 81.3% (65/80), χ2 = 4.44, P < 0.05]. The incidence of complications in the observation group was significantly lower than that in the control group [6.3% (5/80) vs. 16.3% (13/80), χ2 = 4.00, P < 0.05]. Conclusion:The utilization of digital medical 3D technology in the surgical treatment of solid abdominal tumors in children can markedly decrease surgical time, reduce intraoperative blood loss, promote postoperative recovery, achieve a high surgical resection rate, and minimize postoperative complications.

Objective To investigate the effects of circDNMT1 on the proliferation,apoptosis and epithelial-mesenchymal transition(EMT)of triple-negative breast cancer(TNBC)cells by regulating miR-377-3p/PUM1 axis.Methods The TNBC tissues and adjacent normal tissues of 24 patients with TNBC treated in Danzhou People's Hospital from 2018 to 2021 were collected.qRT-PCR and Western blot were used to detect the expression of circDNMT1,miR-377-3p,and PUM1 protein in tissue and mouse normal breast epithelial cell line HC11 and TNBC cell lines 4T1,Eph41424,and JC.4T1 cells were divided into the 4T1 group(untransfected),the si-NC group(transfected with si-NC),the si-DNMT1 group(transfected with si-DNMT1),the si-DNMT1+anti-NC group(simultaneously transfected with si-DNMT1 and anti-NC),and the si-DNMT1+anti-miR-377-3p group(simultaneously transfected with si-DNMT1 and anti-miR-377-3p).qRT-PCR was used to detect the expression of circDNMT1 and miR-377-3p of 4T1 cells in each group;CCK-8 was used to detect the proliferation of 4T1 cells in each group;flow cytometry was used to detect the apoptosis of 4T1 cells in each group;Western blot was used to detect the expression of PUM1,EMT-related proteins and apoptosis-related proteins of 4T1 cells in each group;TargetScan website was used to predict the binding sites of miR-377-3p with circDNMT1 and PUM1;dual luciferase report was used to verify the targeting relationships of miR-377-3p with circDNMT1 and PUM1.After inoculation with 4T1 cells,BALB/c mice were randomly divided into the blank control group(injected with equal amount of normal saline),the negative control group(injected with si-NC via tail vein),the DNMT1 silencing group(injected with si-DNMT1 via tail vein),the combined control group(injected with si-DNMT1 and anti-NC via tail vein),and the combined silencing group(injected with si-DNMT1 and anti-miR-377-3p via tail vein),the tumor massess of mice were recorded and the morphological changes of tumors were observed by hematoxylin-eosin staining.Results circDNMT1 and PUM1 were up-regulated in TNBC tissues and cells,and miR-377-3p was down-regulated.The expression difference was most obvious in 4T1 cells,so 4T1 cells were selected for subsequent experiments.Compared with the 4T1 group and the si-NC group,the expression of miR-377-3p,the apoptosis rate of 4T1 cells,the expression levels of Bax,cleaved caspase-3 and E-cadherin protein of 4T1 cells in the si-DNMT1 group were significantly increased(P<0.05),the circ-DNMT1 level,the expression level of PUM1 protein,OD values at 24 hours and 48 hours,the expression level of Bcl-2,N-cadherin,Vimentin protein were significantly decreased(P<0.05).Compared with the si-DNMT1 group and the si-DNMT1+anti-NC group,the expression of miR-377-3p,the apoptosis rate of 4T1 cells,the expression levels of Bax,cleaved caspase-3 and E-cadherin proteins of 4T1 cells in the si-DNMT1+anti-miR-377-3p group were significantly decreased(P<0.05),the expression level of PUM1 protein,OD values at 24 hours and 48 hours,the expression levels of Bcl-2,N-cadherin,Vimentin proteins were significantly increased(P<0.05).Compared with the miR-NC+WT-circDNMT1 group,the cell luciferase activity in the miR-377-3p mimic+WT-circDNMT1 group was significantly decreased(P<0.05);compared with the miR-NC+WT-PUM1 group,the cell luciferase activity in the miR-377-3p mimic+WT-PUM1 group was significantly decreased(P<0.05).The tumor cells in the blank control group and the negative control group were densely arranged with clear boundary;the tumor cells in the DNMT1 silencing group and the combined control group were loosely arranged,the nuclei were pyknotic,and the cell fragments were increased;the tumor cells in the combined silencing group were densely arranged and the boundaries tended to be clear.Compared with the blank control group and the negative control group,the tumor mass of mice in the DNMT1 silencing group was significantly decreased(P<0.05).Compared with the DNMT1 silencing group and the combined control group,the tumor mass of mice in the combined silencing group was significantly increased(P<0.05).Conclusion Silencing circDNMT1 may inhibit the expression of PUM1 by up-regulating miR-377-3p,thereby inhibiting the proliferation and EMT of TNBC cells,and promoting cell apoptosis.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To compare the short-term outcomes of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants supplementarily fed with fortified donor human milk (DHM) or preterm formula (PF) when the mother's own milk (MOM) is insufficient.Methods:This retrospective cohort study included 91 VLBW or ELBW preterm infants with birth weight<1 500 g who were hospitalized in Peking Union Medical College Hospital from October 1, 2017, to September 30, 2020. Based on the supplemental feeding method when MOM was insufficient, these infants were divided into the DHM group ( n=51) and PF group ( n=40). Mann-Whitney U, t-test, Chi-square test, or Fisher's exact test were used to compare the short-term clinical outcomes during hospitalization between the two groups. Results:(1) There were no statistically significant differences between the 91 preterm infants in the DHM group and PF group in their gestational age, birth weight, sex ratio, birth mode, mothers' age at delivery, or the proportion of infants of small gestational age (all P>0.05). (2) The feeding volume in the DHM group was significantly greater than that in the PF group on the 14th day after birth [(108.2±53.1) vs. (81.0±47.8) ml/(kg·d), t=0.78, P=0.020]. Moreover, the time to achieve the feeding amounts up to 120 ml/(kg·d) and 150 ml/(kg·d) for infants in the DHM group were significantly shorter than those in the PF group [(17.5±10.2) vs. (30.0±12.0) d, t=4.38; (22.1±13.3) vs. (32.3±11.9) d, t=0.02; both P<0.05]; (3) Lower proportion of peripherally inserted central catheter (PICC) [58.8% (30/51) vs. 100% (40/40), χ 2=21.88, P<0.001] and shorter PICC duration were observed in the DHM group [10.0 (0.0-19.0) vs. 29.0 (17.0-40.5) d, Z=5.56, P<0.001] compared to the PF group. The times of red blood cell transfusions and the incidence of late sepsis in the DHM group were less than those in the PF group [0.0 (0.0-2.0) vs. 2.0 (1.0-3.0) times, Z=4.44, P<0.001; 23.5% (12/51) vs. 50.0% (20/40), χ 2=6.39, P=0.011]. There were no statistically significant differences observed in the incidence of bronchopulmonary dysplasia, neonatal necrotizing enterocolitis, retinopathy of prematurity, and the length of hospitalization (all P>0.05). Conclusion:When MOM is insufficient, supplementing VLBW and ELBW infants with fortified donor human milk can shorten the time to achieve enteral nutrition and reduce the use rate and time of PICC, the incidence of late-onset sepsis, and the times of red blood cell transfusion.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg2+ promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated the alveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg2+ promoted the degradation of Kelch-like ECH-associated protein 1(Keap1)and the nucleation of nuclear factor erythroid 2-related factor 2(Nrf2)by up-regulating the expression of sestrin 2(SESN2)in endothelial cells,thus reducing the elevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg2+ promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondrial metabolism.

Objective To investigate the relationship between impaired glucose regulation (IGR) and slow flow or no reflow (SF/NRF) during percutaneous coronary intervention (PCI) in patients with ST segment elevation myocardial infarction (STEMI). Methods Clinical materials of 80 STEMI patients with SF/NRF and 84 STEMI patients without SF/NRF in the hospital from October 2021 to October 2022 were retrospectively collected, including blood glucose, total cholesterol (TC), triglyceride (TG), cardiac troponin Ⅰ (cTnⅠ), fibrinogen, left ventricular ejection fraction (LVEF), D-dimer, uric acid, homocysteine, the ratio of absolute value of neutrophils to absolute value of lymphocytes (NLR), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and 2 h postprandial blood glucose level. Logistic regression model was used to analyze the influencing factors of SF/NRF in STEMI patients with PCI; the receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of fasting blood glucose and 2 h postprandial blood glucose levels for SF/NRF in STEMI patients with PCI. Results Compared with non-SF/NRF group, the levels of cTnⅠ, fibrinogen and HDL-C in SF/NRF group were significantly higher, while the levels of systolic blood pressure (SBP), diastolic blood pressure (DBP) and NLR were significantly lower (P < 0.05). Compared with non-SF/NRF group, the stent diameter, stent length and the time from chest pain to catheter room in SF/NRF group were significantly longer (P < 0.05). The levels of fasting blood glucose and 2 h postprandial blood glucose in SF/NRF group were significantly higher than those in non-SF/NRF group (P < 0.05). Logistic regression analysis showed that fasting blood glucose and 2 h postprandial blood glucose were the influencing factors of SF/NRF in STEMI patients with PCI, and the area under the curve (AUC) of the combination of the two indicators for diagnosis of SF/NRF in STEMI patients during PCI was significantly higher than that by fasting blood glucose and 2 h postprandial blood glucose alone (Z=3.272, 4.369, P < 0.001). Conclusion IGR is related to SF/NRF during PCI in STEMI patients, and fasting blood glucose and 2 h postprandial blood glucose levels are the influencing factors of SF/NRF in STEMI patients.