BACKGROUND:The repair and clinical outcome of bone defects remains a hot and difficult area of clinical research,which is a common problem that plagues clinicians.Constructing suitable,reproducible and infinitely close to clinical animal experimental models and their scientific evaluation are essential for further clinical treatment of related diseases. OBJECTIVE:To retrospectively analyze the preparation methods and characteristics of common animal models of femoral bone defects and to assess their strengths and weaknesses,thereby providing some reference for relevant researchers to select appropriate animal models of femoral bone defects. METHODS:PubMed,Web of Science,Medline,and CNKI were retrieved for relevant literature published from January 1,2000 to August 1,2022.The keywords were"bone defect,bone,bones,defect,defects,defective,animal model,animal,model,laboratory,laboratory animal,animal laboratory"in English and"bone defect,animal model,experiment"in Chinese. RESULTS AND CONCLUSION:Twenty-seven randomized controlled animal experiments involving rats,mice,New Zealand rabbits,and sheep were included,analyzed and assessed.The most common types of bone defects were cylindrical bone defects and segmental osteotomy bone defects,generally found in the middle and distal femur.These models are mostly used to evaluate the effects of bone repair materials,drugs,drug-loaded active substances and physical therapy on bone defect repair and explore defect healing mechanisms,particularly the weight-bearing bone defect repair mechanism.Different defect kinds and femoral bone defect ranges have been found in different animal experiments.Researchers can select the suitable animal model and bone defect type based on the goal of the experiment and then set an acceptable bone defect value.Current studies have shown that cylindrical and segmental osteotomy-induced bone defects,mainly in the distal and middle femur,are mostly used in the animal models of femoral bone defects and that the surgical methods and postoperative management are more mature and operable to provide mature experimental animal models.In terms of cylindrical bone defects,rats and New Zealand rabbits are more suitable,whereas segmental osteotomy has no special requirements and all types of animals can meet the experimental requirements.

BACKGROUND:Heterotopic ossification is a dynamic growth process.Diverse heterotopic ossification subtypes have diverse etiologies or induction factors,but they exhibit a similar clinical process in the intermediate and later phases of the disease.Acquired heterotopic ossification produced by trauma and other circumstances has a high incidence. OBJECTIVE:To summarize the molecular biological mechanisms linked to the occurrence and progression of acquired heterotopic ossification in recent years. METHODS:The keywords"molecular biology,heterotopic ossification,mechanisms"were searched in CNKI,Wanfang,PubMed,Embase,Web of Science,and Google Scholar databases for articles published from January 2016 to August 2022.Supplementary searches were conducted based on the obtained articles.After the collected literature was screened,131 articles were finally included and summarized. RESULTS AND CONCLUSION:(1)The occurrence and development of acquired heterotopic ossification is a dynamic process with certain concealment,making diagnosis and treatment of the disease difficult.(2)By reviewing relevant literature,it was found that acquired heterotopic ossification involves signaling pathways such as bone morphogenetic protein,transforming growth factor-β,Hedgehog,Wnt,and mTOR,as well as core factors such as Runx-2,vascular endothelial growth factor,hypoxia-inducing factor,fibroblast growth factor,and Sox9.The core mechanism may be the interaction between different signaling pathways,affecting the body's osteoblast precursor cells,osteoblast microenvironment,and related cytokines,thereby affecting the body's bone metabolism and leading to the occurrence of acquired heterotopic ossification.(3)In the future,it is possible to take the heterotopic ossification-related single-cell osteogenic homeostasis as the research direction,take the osteoblast precursor cells-osteogenic microenvironment-signaling pathways and cytokines as the research elements,explore the characteristics of each element under different temporal and spatial conditions,compare the similarities and differences of the osteogenic homeostasis of different types and individuals,observe the regulatory mechanism of the molecular signaling network of heterotopic ossification from a holistic perspective.It is beneficial to the exploration of new methods for the future clinical prevention and treatment of heterotopic ossification.(4)Meanwhile,the treatment methods represented by traditional Chinese medicine and targeted therapy have become research hotspots in recent years.How to link traditional Chinese medicine with the osteogenic homeostasis in the body and combine it with targeted therapy is also one of the future research directions.(5)At present,the research on acquired heterotopic ossification is still limited to basic experimental research and the clinical prevention and treatment methods still have defects such as uncertain efficacy and obvious side effects.The safety and effectiveness of relevant targeted prevention and treatment drugs in clinical application still need to be verified.Future research should focus on clinical prevention and treatment based on basic experimental research combined with the mechanism of occurrence and development.

Objective The present study conducted a comprehensive literature review and visualization analysis of both domestic and international research on the utilization of hemodialysis water over the past two decades,aiming to gain insights into the current research status,identify prominent areas of interest,and highlight future development trends in this field,thereby of-fering valuable references for subsequent studies.Methods By employing bibliometric analysis,the relevant literature on hemo-dialysis water usage was retrieved from the Web of Science Core Collection(WoSCC)database and China National Knowledge Network(CNKI)for the period between 2004 and 2024.Subsequently,an in-depth examination of countries,research institu-tions,authors,and keywords associated with these publications was conducted.The visualization map was generated using CiteSpace 6.2.R4 software.Results A total of 3 304 papers were included,with 147 in Chinese and 3 157 in English.Over the past two decades,there has been a consistent upward trend in the number of publications both domestically and international-ly,although the growth rate of domestic literature lags behind that of foreign countries.The United States,China,and Japan rank as the top three countries in terms of publication volume,with the United States exhibiting the highest centrality.Foreign coun-tries tend to form small research groups with close institutional collaborations,while domestic research teams and institutions are relatively dispersed.Currently,foreign research primarily focuses on Fabrication,Ultrafiltration Membranes and Performance;meanwhile,domestic research emphasizes infection control,quality control,and daily maintenance.Conclusion From 2004 to 2024,both domestic and international researchers have consistently focused on water research for hemodialysis.However,China lags behind foreign countries in this field,necessitating enhanced collaboration among nations,institutions,and regions to broad-en the scope and depth of domestic research.

Objective To explore the association between delay discounting and delay aversion with household activities in adult patients with type 2 diabetes mellitus(T2DM).Methods This study was a cross-sectional study.A total of 400 adult patients with T2DM were recruited as the study subjects from the People's Hospital of Linxia Hui Autonomous Prefecture of Gansu Province from February 2023 to June 2023.The face to face survey was conducted to collect the basic data and related information of household activities,delay discounting,delay aversion of the study subjects.The height and weight information was obtained by the phy-sique measurement.The multiple linear regression was adopted to analyze the association between delay dis-counting,delay aversion and the level of household activities.Results After adjusting the sample characteris-tics,the multiple linear regression analysis showed that the delay discounting was negatively correlated with the level of household activities(β=-1.570,95％CI:-3.077 to-0.062),and delay aversion was also nega-tively correlated with the level of household activities(β=-2.442,95％CI:-3.998 to-0.887),and the differences were statistically significant(P＜0.05).Conclusion Both higher delay discounting and higher de-lay aversion are associated with lower levels of household activity.Delay discounting and delay aversion could affect the patients with T2DM to participate in household activities.

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg^-1·d^-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg^-1·d^-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Objective:To investigate the difference between simple posterior interbody fixation and fusion and posterior interbody fixation combined with focus debridement and bone graft fusion for the treatment of mono- and bi-segmental lumbar brucella spondylitis.Methods:A total of 63 patients (42 males and 21 females), aged 50.9±8.18 years (range from 38 to 69 years) with mono- and bi-segmental lumbar brucella spondylitis who received surgical treatment from June 2014 to Feb 2018 were retrospectively analyzed. There were 44 cases of mono-segmental and 19 cases of bi-segmental. Thirty-one cases were treated with single posterior interbody fixation and fusion (PIFF group), and 32 caseswere treated with posterior interbody fixation combined with focus debridement and bone graft fusion (debridement group). The main observation indicators include operation time, intraoperative blood loss, postoperative hospital stay, postoperative medication time, Visual Analogue Scale(VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Frankel score and clinical efficacy.Results:All of 63 patients were followed up for 27.16±6.07 months (range 15 to 38 months). The operation time of mono-segmental patients of PIFF group was 105.86±16.66 min,the intraoperative blood loss was 295.00±55.11 ml, and the postoperative hospitalization was 4.45±1.53 days, which was significantly shorter than debridement group ( P<0.001), while the postoperative medication time was without significant difference between the two groups ( P>0.05). The opration time of bi-segmental patients of PIFF group was 150.33±26.29 min, the intraoperative blood loss was 242.05±50.56 ml, and the postoperative hospitalization was 4.56±1.50 days, which was significantly shorter than debridement group ( P<0.001), while the postoperative medication time was also without significant difference between the two groups. At the last follow-up time, the VAS scores and ODI values of mono- and bi-segments in PIFF group and debridement group were lower than those preoperation, but there was no significant difference between the two groups ( P>0.05). There was no significant difference in CRP between mono-segments of PIFF group and debridement group at the preoperation, 3 months after operation and the last follow-up time ( P>0.05). The CRP in mono-segments of PIFF group and debridement group decreased at 3 months after the operation compared with that preoperation, and the difference was statistically significant ( P<0.001). There was no significant difference in CRP between bi-segments of PIFF group and debridement group at 3 months after operation and the last follow-up time ( P>0.05). There was no significant difference in ESR between mono- and bi-segments of PIFF group and debridement group at 3 months after operation and the last follow-up time ( P>0.05). There was significant difference in ESR between mono- and bi-segments of PIFF group and debridement group at the preoperation, 3 months after operation and the last follow-up time. There was no statistical difference in the proportion of excellent postoperative clinical efficacy between the two groups. Complications were observed in two patients in PIFF group (6.5%, 2/31) compared with 8 patients in debridement group (25%, 8/32, χ2=4.057, P=0.044). Conclusion:On the basis of standardized anti-brucella drug therapy, simple posterior interbody fixation and fusion for the treatment of brucella spondylitis has a satisfactory surgical effect, and has the advantages of less surgical trauma, shorter time, earlier postoperative movement time and fewer complications.

Objective:To explore the epidemiological characteristics and the antibiotic resistance of Streptococcus pneumoniae isolates, and to provide the evidence for the rational use of antimicrobial agents to treat Streptococcus pneumoniae infection. Methods:The positive microbiological laboratory identification and antimicrobial susceptibility testing of Streptococcus pneumoniae from sputum of children with respiratory infections during January 2010 to December 2017 in Children′s Hospital of Soochow University were retrospectively analyzed. The positive rates of Streptococcus pneumoniae of different genders, ages, years and seasons were compared. The annual detection rates and trends of drug resistance of Streptococcus pneumoniae to penicillin, amoxicillin and cefotaxime were analyzed by Mann-Kendall trend test. The seasonal decomposition of time series was conducted to assess the association between Streptococcus pneumoniae detection rate and season. Enumeration data was compared using χ2 test. Results:Of the 88 480 sputum specimens, the total positive rate of Streptococcus pneumoniae was 10.3%(9 081/88 480). The detection rates of Streptococcus pneumoniae in children aged 0 to <0.5 years old, 0.5 to <2 years old, 2 to <3 years old, 3 to <5 years old, and 5 to <15 years old were 4.2%(1 407/33 224), 13.1%(3 191/24 390), 14.9%(2 417/16 252), 17.9%(1 474/8 246) and 9.3%(592/6 368), respectively. The difference was statistically significant ( χ2=2 421.6, P<0.01). The detection rates were 8.1%(1 321/16 306) from January to March, 10.9%(2 194/20 207) from April to June, 8.5%(2 141/25 058) from July to September, and 12.7%(3 425/26 909) from October to December. The discrepancy of positive rates in different seasons showed statistical significance ( χ2=311.5, P<0.01). During 2010 to 2017, significant decreases in antibiotic resistant rates of Streptococcus pneumoniae to penicillin, amoxicillin and cefotaxime were detected (tau=-0.93, -0.93 and -0.71, respectively, all P<0.05). Conclusions:The detection rate of Streptococcus pneumoniae in sputum of children with respiratory infections may present seasonal pattern and vary between different ages of children. The resistance to β-lactam antibiotics has declined.

The aim of this study was to screen the active regions and transcription factor binding sites in the promoter of the CBD103 gene related to Arctic fox coat color, and to provide a basis for revealing the molecular genetic mechanism of CBD103 gene regulating the coat color formation. The 5'-flanking region fragment 2 123 bp of Arctic fox CBD103 gene was cloned, and 4 truncated promoter reporter vectors of different lengths were constructed. The promoter activity was detected by the dual-luciferase reporter assay system. Point mutations were performed on the 3 predicted specificity protein 1 (Sp1) transcription factor binding sites in the highest promoter active region, and 3 mutant vectors were constructed. The activity was then detected by the dual-luciferase reporter assay system. The results showed that the region 1 656 (-1 604/+51) had the highest activity in the 4 truncated promoters of different lengths, and the promoter activity of the three mutant vectors constructed in this region were significantly lower than that of the wild type (fragment 1 656). The region of -1 604 /+51 was the core promoter region of CBD103 gene in Arctic fox and -1 552/-1 564, -1 439/-1 454 and -329/-339 regions were positive regulatory regions. This study successfully obtained the core promoter region and positive regulation regions of the Arctic fox CBD103 gene, which laid a foundation for further study on the molecular genetic mechanism of this gene regulating Arctic fox coat color.
Animals ; Binding Sites ; Foxes ; Luciferases ; Promoter Regions, Genetic ; Sp1 Transcription Factor ; beta-Defensins

It is important to find the patients with malnutrition or at risk of malnutrition,so that the appropriate nutrition support would be given in time.The nutritional status of inpatients isexamined by various nutrition assessment methods and laboratory indexes.If necessary,when the patient sare discharged the home enteral nutrition therapy should be given under the supervision of community doctors and nurses following the established nutrition support program.With this program the nutritional status can be further improved,the disease recovery and quality of life can be promoted,as well as the economical burden of patients can be reduced.