OBJECTIVE To prepare reactive oxygen species （ROS）-responsive methotrexate （MTX）-modified paclitaxel （PTX）/icariin （ICA） micelles （MTX-oxi-Ms@PTX/ICA）， and perform technology optimization and in vitro anti-tumor effect evaluation. METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test. The micelles were prepared by thin film hydration method， and their technology was optimized by response surface methodology. The fundamental characteristics of the micelles prepared by the optimal technology were evaluated. The micelles’ cytotoxicity， targeting ability to renal carcinoma RENCA cells of mice， and their inhibitory effects on invasion and migration were assessed. RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L. The optimal technology of MTX-oxi-Ms@PTX/ ICA was determined to include 80 mg Soluplus®， Soluplus® and TPGS1000 mass ratio of 4∶1 （mg/mg）， 2 mg DSPE-PEG2000-TK- PEG5000， 2 mg DSPE-PEG2000-MTX， 1 mg PTX， and 1.5 mg ICA， with a hydration temperature of 35 ℃ and a formulation volume of 5 mL. Under the optimal conditions， average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi- Ms@PTX/ICA reached 92.75%， the critical micelle concentration （CMC） was 0.007 9 mg/mL， the particle size was （62.09±1.68） nm， the polydispersity index （PDI） was 0.046±0.032， and the Zeta potential was （－2.47±0.15） mV. Within 30 days of placement， there was no significant change E-mail：yingqiang_1126@163.com in particle size and polydispersity index of micelle. In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments. The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was （5.170±0.036） μmol/L. In vitro cellular uptake experiments indicated that compared with unmodified micelles， MTX modified micelles had stronger targeting effects on cancer cells， and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells （P＜0.05）. CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared， which exhibit high encapsulation efficiency， low critical micelle concentration， and good stability. These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.

Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Sesquiterpenes are natural terpenes containing 15 carbon atoms. They are widely used in the perfume, pharmaceutical, and biofuel industries due to their remarkable biological activities. The traditional production of sesquiterpenes relies on chemical synthesis or plant extraction, which has the disadvantages of low yields and waste of resources. The construction of microbial cell factories for the efficient synthesis of sesquiterpenes by means of synthetic biology provides a new option. In recent years, with the development of metabolic engineering and synthetic biology, the heterologous synthesis of a variety of sesquiterpenes has been successfully achieved by metabolic engineering of the oleaginous yeast, Yarrowia lipolytica. In this paper, we review the research progress in the heterologous synthesis of different sesquiterpenes by Y. lipolytica, discuss the synthetic biology strategies commonly used in this field, and make an outlook on the research directions and engineering approaches to further enhance the sesquiterpene yield in this host. This paper provides a reference for strategies such as synergistic optimization of synthetic biology and metabolic engineering, enhanced precursors, and opens up new directions for the application of synthetic biology in green chemistry and sustainable production.
Yarrowia/genetics* ; Sesquiterpenes/metabolism* ; Metabolic Engineering/methods* ; Synthetic Biology/methods*

Seeds are the source for the production of Chinese medicinal materials. The seed authenticity and quality of directly affect the effectiveness and safety of Chinese medicinal materials. The seed quality is faced with the problems such as mixed sources， existence of adulterants and seeds stocked for years， low maturity， and low purity. To ensure the high-quality and sustainable development of the Chinese medicinal material industry， it is urgent to standardize the seed market and identify and evaluate the quality of the seeds circulating in the market. Seed identification methods include visual inspection， microscopic observation， micro-character identification， chemical fingerprinting， molecular identification， electronic nose， X-ray diffraction， electrochemical fingerprinting， spectral imaging， and artificial intelligence. These methods have different application scopes and unique advantages and disadvantages. According to the different species of Chinese herbal medicines and different requirements of testing sites， suitable methods can be selected to achieve rapid and accurate identification with low costs. In the future， the seed identification methods should be developed based on emerging technologies with interdisciplinary knowledge， and intelligent， nondestructive， and single-grain detection methods are needed for the modern Chinese medicinal material industry. This paper introduces the seed identification technologies currently applied in research and production， compares the principles， applicability， advantages， and disadvantages of different technologies， and provides an outlook on the future development of seed identification technologies， aiming to provide a reference for the identification and quality evaluation of seeds of Chinese medicinal material.

ObjectiveTo establish a method based on specific polymerase chain reaction （PCR） that can accurately and rapidly identify Astragalus membranaceus var. mongholicus （AMM） seeds and A. membranaceus （AM） seeds. MethodThe Chloroplast Genome Information Resource （CGIR） and IdenDSS were used to obtain the characteristic DNA fragments of AMM and AM， and the specific single nucleotide polymorphism （SNP） sites of AMM and AM were screened out， on the basis of which the specific primers MG-F/MG-R of AMM and MJ-F/MJ-R of AM were designed. The specific PCR method for identifying AMM and AM was established and optimized， and the specificity and applicability of the method were investigated. ResultThe specific PCR conditions for the identification of AMM were primers MG-F/MG-R， annealing at 62 ℃， and 28 cycles. After PCR amplification and gel electrophoresis， the specific band appeared at about 220 bp， with no band for the seeds of AM or adulterants. The specific PCR conditions for identifying the AM were primers MJ-F/MJ-R， annealing at 58 ℃， and 28 cycles. After PCR amplification and gel electrophoresis， the band appeared at about 150 bp， with no band of AMM or adulterants. ConclusionThe specific PCR method established in this study can accurately and quickly identify the seeds of AMM and AM， which provides a basis for the classification and accurate identification of Astragalus seeds and adulterants.

Objective:To establish the standard of nursing quality in bone oncology department, and provide the basis for scientific evaluation of nursing quality in bone oncology department.Methods:On the theoretical basis of Donabedian′s three-dimensional quality model of "structure-process-outcome", and through literature review and semi-structured interview method, the "evaluation index of nursing quality in bone oncology department" was preliminatively formulated from November 2022 to June 2023. The Delphi method was used to select 31 experts from 31 third-level A hospitals and nursing colleges in 27 provinces or municipalities across the country for two rounds of correspondence consultation. The criteria were screened and modified to determine the evaluation criteria of nursing quality in bone tumor specialty.Results:The questionnaire recovery rate of 2 rounds of expert consultation was 100.00%, the authority coefficient of 2 rounds of expert consultation was 0.93, and the coefficient of variation of 1, 2 and 3-grade standards were all less than or equal to 0.25. The Kendall′s coefficient of concordance of the primary standards of the two rounds of expert consultation were both 0.088, in the secondary standards were 0.103 and 0.140, in the tertiary standards were 0.119 and 0.110. Through 2 rounds of expert letter consultation, the evaluation criteria for the quality of care in bone tumor specialties were divided into three levels, including 3 primary standards (structural quality criteria, process quality criteria and outcome quality criteria), 21 secondary standards and 80 tertiary standards.Conclusions:The construction process of nursing quality standard in bone oncology department is scientific and reliable, reflecting specialty characteristics, and can provide scientific basis for the evaluation of nursing quality in bone oncology department and standardize nursing behavior.

BACKGROUND:At present,wrist protection products designed in and outside China have not solved the contradiction between protecting the wrist joint from injury and maintaining the flexible movement of the wrist joint. OBJECTIVE:To investigate the biomechanical mechanism of dorsiflexion injury of the wrist joint in elderly people after falls,and to provide a biomechanical basis for the prevention and treatment of wrist injury in elderly people after falls. METHODS:A 65-year-old man was selected to obtain the original data by uninterrupted CT scan of the middle and lower 2/3 of his left forearm up to the end of the finger.A finite element model of wrist dorsiflexion was established using ANSYS 12.0 finite element software.The palm surface of the model was constrained,and the model at a velocity load of 2 m/s in the direction of vertical downward was given to simulate the injury state of the palm when the elderly fall.The stress distribution of the soft tissues and bones of the wrist joint and the change of the stress with time were observed after the load was applied. RESULTS AND CONCLUSION:(1)A realistic and effective finite element model of the dorsal extension position of the wrist joint of the elderly was established.The soft tissue stresses were mainly concentrated in the small fissure of the palm and the dorsal side of the wrist after loading.The skeletal stresses were mainly concentrated in the lower end of the ulnar radius dorsally.The stresses in the lower end of the radius were the greatest.The palmar stresses were mainly concentrated in the middle and lower 1/3 of the radius and the hook bone.The stress distribution of the ulnar radius was asymmetric,and the stresses in the radius were more concentrated.(2)The results of the study are consistent with the clinical situation of a fallen wrist injury in elderly people,and can be used to explain the mechanism of wrist dorsiflexion injury,which can provide the biomechanical basis for the design of wrist protection devices that can be used to prevent wrist injury induced by falling and the treatment of wrist injury in elderly people.

Objective:To explore the effectiveness of the Shewhart control chart-based assessment and early warning system in prevention of medical device-related pressure injury(MDRPI).Methods:152 critically ill patients admitted to Hebei Central Hospital from January 2020 to December 2021 were selected and divided into a control group and an observation group based on different methods of assessing MDRPI risk,with 76 cases in each group.The control group adopted the Braden scale to assess the risk of MDRPI.The observation group adopted a safety early warning system based on Shewhart control charts to assess the risk of MDRPI in patients.Nursing measures were undertaken according to MDRPI risk grade in both groups.The occurrence of adverse events of MDRPI,nursing safety quality and nursing comprehensive quality were compared between the two groups.Results:The incidence rate of head,neck and face adverse events of MDRPI and the total incidence of adverse events of MDRPI of the patients in the observation group were lower than those in the control group(x2=4.802,5.758,P<0.05).The safety quality and comprehensive quality of nursing of 20 nurses in the observation group were higher than those in the control group(t=6.654,7.172,P<0.05).Conclusion:The application of assessment and early warning system based on Shewhart control chart in clinical nursing management can effectively reduce the incidence of MDRPI adverse events and improve the quality of nursing safety and comprehensive nursing.

Objective:To evaluate the development of fetal cerebral sulci and gyrus and the blood perfusion in pregnant women with gestational diabetes mellitus(GDM) by ultrasound.Methods:A total of 1 540 pregnant women with 28-34 weeks of pregnancy who underwent systematic screening in Henan Provincial People′s Hospital from January 2022 to October 2022 were prospectively selected, 100 pregnant women with GDM were selected as the GDM group. According to the effect of blood glucose control, the GDM group was divided into 2 groups: the satisfied control group (GDM group 1), and the dissatisfied control group (GDM group 2), with 50 cases in each group. At the same period, 50 healthy pregnant women at 28-34 weeks of gestation were enrolled as the control group. The differences of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci among the 3 groups were statistically analyzed. And the correlations between the deep of the brain cerebral sulci and gyrus and controlled blood glucose levels were evaluated. The umbilical artery pulsation index(UAPI), middle cerebral artery pulsation index(MCAPI) and ductus venosus pulsation index(DVPI) among the 3 groups were compared, and the differences in fetal blood perfusion among the 3 groups were evaluated.Results:There were no significant differences in the depths of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci between the control group and the GDM group 1 (all P>0.05), and they were larger than those of the GDM group 2 (all P<0.05). The depths of lateral fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus were negatively correlated with fasting blood glucose, 1 h and 2 h postprandial blood glucose (all P<0.05). There were no significant differences in MCAPI, UAPI and DVPI between the control group and GDM1 group (all P>0.05). The MCAPI in GDM 2 group was lower than that in the control group and GDM 1 group, and the UAPI and DVPI values were higher than those in the control group and GDM1 group(all P<0.05). Conclusions:The maturity of fetal cerebral sulci and gyrus in GDM pregnant women is related to the blood glucose control of pregnant women. The change of blood perfusion caused by persistent hyperglycemia in pregnant women and intrauterine hypoxia may cause the development retardation of cerebral sulci and gyrus.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.