BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

Objective:To visualize and analyze the literature related to nurses′ psychological contract at home and abroad by CiteSpace software, discuss the development trend, and to provide reference for subsequent research.Methods:Literature related to nurses′ psychological contract collected by China National Knowledge Infrastructure and Web of Science from the establishment of the database to August 31, 2023 were retrieved. CiteSpace software was used to visually process the authors, institutions, keywords, publication trends and other types of nodes. Combined with the visualization map, the research status and hot trends of nurses′ psychological contract were analyzed.Results:A total of 175 articles in English and 126 articles in Chinese were included. The annual publication volume showed a zigzag upward trend. Chen Furong′s team published the most Chinese literature, while Rodwell J′s team published the most English literature. Shanxi Medical University and Monash University were the research institutions with the largest number of publications in Chinese and English respectively. Domestic research hotspots mainly focused on 5 directions: the status quo investigation, influence factors, intervention strategies, the impact on performance behavior, the content and structure of nurses′ psychological contract. Foreign research hotspots mainly focused on 3 directions: the influence factors, intervention strategies and the impact on performance behavior.Conclusions:The overall number of papers published in the field of nurses′psychological contract research at home and abroad is small, and the depth and breadth of the research are far from enough. The cooperation between authors and institutions should be strengthened, the research direction should be more diversified, and the mediation effect analysis and influence mechanism research of psychological contract should be paid attention to, so as to construct a multipath nurses′psychological contract system complied with national condition.

The application of pesticides(mostly insecticides and fungicides)during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea.Thus,it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits.However,the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues.In this study,nine types of lateral flow immunochromatographic strips(LFICSs)were developed to detect the pesticides of interest(fenpropathrin,chlorpyrifos,imidacloprid,thiamethoxam,acet-amiprid,carbendazim,chlorothalonil,pyraclostrobin,and iprodione).To reduce the interference of tea substrates on the assay sensitivity,the pretreatment conditions for tea samples,including the extraction solvent,extraction time,and purification agent,were optimized for the simultaneous detection of these pesticides.The entire testing procedure(including pretreatment and detection)could be completed within 30 min.The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.

【Objective】 To study the platelet transfusion predictive models in tumor patients and evaluate its application effect. 【Methods】 A retrospective study was conducted on 944 tumor patients, including 533 males and 411 females who received platelet transfusion in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, the Affiliated Cancer Hospital of Xinjiang Medical University and Kailuan General Hospital from August 2022 to January 2023. Multivariate Logistic regression analysis was used to establish the platelet transfusion predictive models, and Medcalc15.8 software was used to draw the receiver operating curve (ROC) to evaluate the application effect of the prediction model. The actual application effect of models was verified through 162 female clinical cases and 172 male clinical cases. 【Results】 The incidence of platelet transfusion refractoriness in tumor patients was 28.9% (273/944), with 33.2% (177/533) in males, significantly higher than that in females [23.4% (96/411)] (P<0.05). Platelet transfusion predictive models: Y1 (female) =-8.546+ (0.581×number of pregnancies) + (0.964×number of inpatient transfusion bags) + number of previous platelet transfusion bags (5-9 bags: 1.259, ≥20 bags: 1.959) + clinical diagnosis (lymphoma: 2.562, leukemia: 3.214); Y2 (male) =-7.600+ (1.150×inpatient transfusion bags) + previous platelet transfusion bags (10-19 bags: 1.015, ≥20 bags: 0.979) + clinical diagnosis (lymphoma: 1.81, leukemia: 3.208, liver cancer: 1.714). Application effect evaluation: The AUC (area under the curve), cut-off point, corresponding sensitivity and specificity of female and male platelet transfusion effect prediction models were 0.868, -0.354, 68.75%, 89.84% and 0.854, -0.942, 81.36%, 77.53%, respectively. Actual application results showed that the sensitivity, specificity, and accuracy of female and male model were 89.47%, 92.74%, 91.98% and 83.72%, 91.47%, 89.53%, respectively. 【Conclusion】 There is high incidence of platelet transfusion refractoriness in tumor patients, and the predictive model has good prediction effect on platelet transfusion refractoriness in tumor patients, which can provide reliable basis for accurate platelet transfusion in tumor patients.

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 ( 2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 ( 3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.

Stroke is the most common disease of the central nervous system, with high disability and mortality, which seriously affects the quality of life of patients and causes a huge disease burden. However, the overall treatment effect is still unsatisfied at present. Myeloperoxidase (MPO), a kind of peroxidase derived from neutrophils, may play an important role in stroke development through many ways, and has great potential in early diagnosis, clinical treatment and prognosis evaluation of stroke. This article reviews the research progress of MPO in stroke, aiming to provide new ideas for better diagnosis and treatment of stroke in clinic.

Objective:To investigate the differences of umbilical vein diameter(D), time average peak velocity(TAmax) and blood flow between congenital heart disease and normal fetus.Methods:The umbilical vein diameter and time average peak velocity of 69 fetuses with congenital heart disease (disease group) from 22 to 27 weeks were prospectively studied in Maternal-Fetal Medical Center in Fetal Heart Disease of Beijing Anzhen Hospital from May 2021 to September 2021. Q 1 (umbilical venous blood flow) was calculated according to the formular [Q=0.5TAmax·π·(D/2) 2)], and Q 2 (Q 2=Q 1/weight) was calculated according to the fetal weight. At the same time, 111 normal fetuses with matched gestational age were selected as control group. The differences of fetal umbilical vein D, TAmax, Q 1 and Q 2 between the two groups were analyzed. Results:The inner diameter of umbilical vein D, TAmax, Q 1 and Q 2 in the congenital heart disease group were lower than those in the control group(all P<0.05). In the control group, the inner diameter of umbilical vein D, TAmax and Q 1 increased with the increase of gestational age and showed a positive linear correlation( r=0.608, 0.320, 0.626; all P≤0.001), while there was no obvious linear correlation between Q 2 and gestational age( r=0.189, P=0.047). Conclusions:The decrease of umbilical vein D, TAmax, Q 1 and Q 2 in the fetus with congenital heart disease indicates the decrease of effective blood flow in placenta-fetus circulation, which indirectly reflects the decrease of placental function in the fetus with congenital heart disease.

Natural cyclohexapeptide AFN A₁ fromStreptomyces alboflavus 313 has moderate antibacterial and antitumor activities. An artificial designed AFN A₁ homodimer, di-AFN A₁, is an antibiotic exhibiting 10 to 150 fold higher biological activities, compared with the monomer. Unfortunately, the yield of di-AFN A₁ is very low (0.09 ± 0.03 mg·L^-1) in the engineered strain Streptomyces alboflavus 313_hmtS (S. albo/313_hmtS), which is not friendly to be genetically engineered for titer improvement of di-AFN A₁ production. In this study, we constructed a biosynthetic gene cluster for di-AFN A₁ and increased its production through heterologous expression. During the collection of di-AFN A₁ biosynthetic genes, the afn genes were located at three sites of S. alboflavus 313 genome. The di-AFN A₁ biosynthetic gene cluster (BGC) was first assembled on one plasmid and introduced into the model strain Streptomyces lividans TK24, which produced di-AFN A₁ at a titer of 0.43 ± 0.01 mg·L^-1. To further increase the yield of di-AFN A₁, the di-AFN A₁ BGC was multiplied and split to mimic the natural afn biosynthetic genes, and the production of di-AFN A₁ increased to 0.62 ± 0.11 mg·L^-1 in S. lividans TK24 by the later strategy. Finally, different Streptomyces hosts were tested and the titer of di-AFN A₁ increased to 0.81 ± 0.17 mg·L^-1, about 8.0-fold higher than that in S. albo/313_hmtS. Successful heterologous expression of di-AFN A₁ with a remarkable increased titer will greatly facilitate the following synthetic biological study and drug development of this dimeric cyclohexapeptide.
Cloning, Molecular ; Streptomyces/metabolism* ; Multigene Family ; Anti-Bacterial Agents/metabolism* ; Plasmids/genetics*

Objective:To investigate the value of post left atrium space index (PLASI) in the diagnosis of fetal isolated total anomalous pulmonary venous connection (TAPVC).Methods:Twenty-six cases of fetal isolated TAPVC were retrospectively analyzed as the TAPVC group and 243 normal fetuses were selected as the control group from October 2012 to April 2019 in the Consultation Center of Maternal-Fetus Medicine in Fetal Heart Disease in Beijing An Zhen Hospital. The width of the PLAS and the diameter of the descending aorta were measured in the four chamber view, and then the PLAS index (PLASI) (the width of the PLAS/the diameter of the descending aorta) was calculated. The relationships between the width of PLAS, the diameter of descending aorta and the PLASI and gestational age were analyzed. The difference of the PLASI between isolated TAPVC group and control group was analyzed, and ROC curve was used to analyze the sensitivity and specificity in identifying the isolated TAPVC fetuses and normal fetuses.Results:In the 243 normal fetuses in control group, both the width of the PLAS and the diameter of the descending aorta increased with gestational age ( r s=0.362, 0.648, P<0.05). There was no statistically significant correlation between the PLASI and gestational age ( r s=-0.065, P>0.05). The PLAS and the PLASI in isolated TAPVC group were all significantly higher than those in control group ( t=26.31, 34.90, P<0.01). Based on the ROC curve analysis, when the cutoff value was set to 3.6 mm, the sensitivity and specificity of PLAS in identifying isolated TAPVC and normal fetuses were 97.5% and 100%, respectively. When the cutoff value was set to 1.1, the sensitivity and specificity of PLASI in identifying isolated TAPVC and normal fetuses were 100% and 100%, respectively. Conclusions:The PLASI is a sensitive parameter in identifying the isolated TAPVC, which is helpful for the rapid screening of the isolated TAPVC.