Historic dog furs unravel the origin and artificial selection of modern Nordic Lapphund and Elkhound dog breeds.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100-200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

Transcriptomic and intervention evidence reveals domestic dogs as a promising model for anti-inflammatory investigation.

Domestic dogs have great potential to expand our understanding of the determinants of aging. To understand the aging pattern of domestic dogs and evaluate whether they can be used as an aging model, we performed RNA sequencing on white blood cells from domestic dogs aged 1-9 years and treated aged dogs with classical antiaging approaches. We obtained 30 RNA sequencing libraries and identified 61 age-associated genes with dynamic changes, the majority of which were related to metabolism and immune function, which may be predominant biomarkers for aging in dogs. We next treated aged dogs with canine mesenchymal stem cells (cMSCs), nicotinamide mononucleotide, and rapamycin to determine whether and how they responded to the antiaging interventions. The results showed that these treatments can significantly reduce the level of inflammatory factors (IL-6 and TNF-α). MSCs effectively improved the heart functions of aged dogs. Three key potential age-related genes (PYCR1, CCRL2, and TOX) were reversed by MSC treatment, two of which (CCRL2 and TOX) are implicated in immunity. Overall, we profiled the transcriptomic pattern of domestic dogs and revealed that they may be a good model of aging, especially in anti-inflammatory investigations.

Establishment of nonobstructive coronary microcirculatory disorders in rabbits using three established methods and a comparative study.

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (ß, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.

Metformin improves nonalcoholic fatty liver disease in db/db mice by inhibiting ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is the primary complication of type 2 diabetes (T2DM)-related liver disease, lacking effective treatment options. Metformin (Met), a widely prescribed anti-hyperglycemic medication, has been found to protect against NAFLD. Ferroptosis, a newly discovered form of cell death, is associated with the development of NAFLD. Despite this association, the extent of Met's protective effects on NAFLD through the modulation of ferroptosis has yet to be thoroughly investigated. In the present study, the administration of erastin or Ras-selective lethal 3 (RSL3), both known ferroptosis inducers, resulted in elevated cell mortality and reduced cell viability in AML12 hepatocytes. Notably, Met treatment demonstrated the capacity to mitigate these effects. Furthermore, we observed increased ferroptosis levels in both AML12 hepatocytes treated with palmitate and oleate (PA/OA) and in the liver tissue of db/db mice. Met treatment demonstrated significant reductions in iron accumulation and lipid-related reactive oxygen species production, simultaneously elevating the glutathione/glutathione disulfide ratio in both PA/OA-treated AML12 hepatocytes and the liver tissue of db/db mice. Interestingly, the anti-ferroptosis effects of Met were significantly reversed with the administration of RSL3, both in vitro and in vivo. Mechanistically, Met treatment regulated the glutathione peroxidase 4/solute carrier family 7 member 11/acyl-CoA synthetase long-chain family member 4 axis to alleviate ferroptosis in NAFLD hepatocytes. Overall, our findings highlight the crucial role of ferroptosis in the development of T2DM-related NAFLD and underscore the potential of Met in modulating key factors associated with ferroptosis in the context of NAFLD.

Association between the Khorana risk score and all-cause mortality in Japanese patients with gastric and colorectal cancer: A retrospective cohort study.

BACKGROUND: The Khorana risk score (KRS) has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer. Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited. AIM: To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity. METHODS: Data from Dryad database were used in this study. Patients in the Gastroenterology Department of Sapporo General Hospital, Sapporo, Japan, were enrolled. The starting and ending dates of the enrollment were January 1, 2008 and January 5, 2015, respectively. The cutoff date for follow-up was May 31, 2016. The independent and dependent (target) variables were the baseline measured using the KRS and final all-cause mortality, respectively. The KRS was categorized into three groups: Low-risk group (= 0 score), intermediate-risk group (1-2 score), and high-risk group (≥ 3 score). RESULTS: Men and patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS. The higher the score, the higher the risk of early death; however, the relevance of this independent prediction decreased with longer survival. The overall survival of each patient was recorded via real-world follow-up and retrospective observations, and this study yielded the overall relationship between KRS and all-cause mortality. CONCLUSION: The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years; however, this independent predictive relationship weakened as survival time increased.

Cost-effectiveness of drug treatment for young and middle-aged stage 1 hypertensive patients with high risk.

Background: Drug treatment was recommended for stage 1 hypertensive patients (blood pressure of 130-139 / 80-89 millimetres of mercury (mmHg)) with high cardiovascular disease (CVD) risk in the 2017 Hypertension Clinical Practice Guidelines, 2018 Chinese guidelines and 2021 World Health Organization guidelines, but not in other guidelines. However, evidence on the cost-effectiveness of drug treatment among young and middle-aged patients remains scarce. This study aimed to compare the cost-effectiveness of drug treatment vs. non-drug treatment for stage 1 hypertensive patients aged <60 years with high CVD risk. Methods: A microsimulation model projected quality-adjusted life years (QALYs), health care costs, and incremental cost-effectiveness ratios for drug treatment from a societal perspective. Transition probabilities were estimated from the Kailuan study with a sample size of 34 093 patients aged <60 years with high CVD risk. Costs and health utilities were obtained from the Kailuan study, national statistics reports and published literature. Results: Over a 15-year time horizon, the model predicted that drug treatment generated QALY of 9.36 and was associated with expected costs of 3735 US dollars ($) compared with 9.07 and $3923 produced by non-drug treatment among stage 1 hypertensive patients, resulting in a cost-saving for drug treatment. At a willingness-to-pay threshold of $10439/QALY (one gross domestic product (GDP) per capita in 2020), drug treatment had a 99.99% probability of being cost-effective for 10 000 samples of probabilistic sensitivity analysis. Sensitivity analyses by different values of transition probability, cost, utility and discount rate did not appreciably change the results. Shortening the time horizon to the average follow-up period of eight years resulted in ICER of $189/QALY for drug treatment (<1 × GDP/QALY). Conclusions: Our results suggested that drug treatment was a dominant strategy for stage 1 hypertensive patients aged <60 years with high CVD risk in China, which may provide evidence for policymakers and clinicians when weighing the pros and cons of drug treatment for young and middle-aged stage 1 hypertensive patients.

Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing.

Despite intensive studies in modeling neuropsychiatric disorders especially autism spectrum disorder (ASD) in animals, many challenges remain. Genetic mutant mice have contributed substantially to the current understanding of the molecular and neural circuit mechanisms underlying ASD. However, the translational value of ASD mouse models in preclinical studies is limited to certain aspects of the disease due to the apparent differences in brain and behavior between rodents and humans. Non-human primates have been used to model ASD in recent years. However, a low reproduction rate due to a long reproductive cycle and a single birth per pregnancy, and an extremely high cost prohibit a wide use of them in preclinical studies. Canine model is an appealing alternative because of its complex and effective dog-human social interactions. In contrast to non-human primates, dog has comparable drug metabolism as humans and a high reproduction rate. In this study, we aimed to model ASD in experimental dogs by manipulating the Shank3 gene as SHANK3 mutations are one of most replicated genetic defects identified from ASD patients. Using CRISPR/Cas9 gene editing, we successfully generated and characterized multiple lines of Beagle Shank3 (bShank3) mutants that have been propagated for a few generations. We developed and validated a battery of behavioral assays that can be used in controlled experimental setting for mutant dogs. bShank3 mutants exhibited distinct and robust social behavior deficits including social withdrawal and reduced social interactions with humans, and heightened anxiety in different experimental settings (n = 27 for wild-type controls and n = 44 for mutants). We demonstrate the feasibility of producing a large number of mutant animals in a reasonable time frame. The robust and unique behavioral findings support the validity and value of a canine model to investigate the pathophysiology and develop treatments for ASD and potentially other psychiatric disorders.

Differential effects of social isolation on oligodendrocyte development in different brain regions: insights from a canine model.

Social isolation (SI) exerts diverse adverse effects on brain structure and function in humans. To gain an insight into the mechanisms underlying these effects, we conducted a systematic analysis of multiple brain regions from socially isolated and group-housed dogs, whose brain and behavior are similar to humans. Our transcriptomic analysis revealed reduced expression of myelin-related genes specifically in the white matter of prefrontal cortex (PFC) after SI during the juvenile stage. Despite these gene expression changes, myelin fiber organization in PFC remained unchanged. Surprisingly, we observed more mature oligodendrocytes and thicker myelin bundles in the somatosensory parietal cortex in socially isolated dogs, which may be linked to an increased expression of ADORA2A, a gene known to promote oligodendrocyte maturation. Additionally, we found a reduced expression of blood-brain barrier (BBB) structural components Aquaporin-4, Occludin, and Claudin1 in both PFC and parietal cortices, indicating BBB disruption after SI. In agreement with BBB disruption, myelin-related sphingolipids were increased in cerebrospinal fluid in the socially isolated group. These unexpected findings show that SI induces distinct alterations in oligodendrocyte development and shared disruption in BBB integrity in different cortices, demonstrating the value of dogs as a complementary animal model to uncover molecular mechanisms underlying SI-induced brain dysfunction.

Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture.

BACKGROUND: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 × data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function. RESULTS: We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection. CONCLUSIONS: We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.

Multiple Origins and Genomic Basis of Complex Traits in Sighthounds.

Sighthounds, a distinctive group of hounds comprising numerous breeds, have their origins rooted in ancient artificial selection of dogs. In this study, we performed genome sequencing for 123 sighthounds, including one breed from Africa, six breeds from Europe, two breeds from Russia, and four breeds and 12 village dogs from the Middle East. We gathered public genome data of five sighthounds and 98 other dogs as well as 31 gray wolves to pinpoint the origin and genes influencing the morphology of the sighthound genome. Population genomic analysis suggested that sighthounds originated from native dogs independently and were comprehensively admixed among breeds, supporting the multiple origins hypothesis of sighthounds. An additional 67 published ancient wolf genomes were added for gene flow detection. Results showed dramatic admixture of ancient wolves in African sighthounds, even more than with modern wolves. Whole-genome scan analysis identified 17 positively selected genes (PSGs) in the African population, 27 PSGs in the European population, and 54 PSGs in the Middle Eastern population. None of the PSGs overlapped in the three populations. Pooled PSGs of the three populations were significantly enriched in "regulation of release of sequestered calcium ion into cytosol" (gene ontology: 0051279), which is related to blood circulation and heart contraction. In addition, ESR1, JAK2, ADRB1, PRKCE, and CAMK2D were under positive selection in all three selected groups. This suggests that different PSGs in the same pathway contributed to the similar phenotype of sighthounds. We identified an ESR1 mutation (chr1: g.42,177,149 T > C) in the transcription factor (TF) binding site of Stat5a and a JAK2 mutation (chr1: g.93,277,007 T > A) in the TF binding site of Sox5. Functional experiments confirmed that the ESR1 and JAK2 mutation reduced their expression. Our results provide new insights into the domestication history and genomic basis of sighthounds.

Impacts of gait biomechanics of patients with thoracolumbar kyphosis secondary to Scheuermann's disease.

Introduction: Thoracolumbar kyphosis (TLK) is a common feature in patients with spinal deformities. However, due to limited studies, the impacts of TLK on gait have not been reported. The objective of the study was to quantify and evaluate the impacts of gait biomechanics of patients with TLK secondary to Scheuermann's disease. Methods: Twenty cases of Scheuermann's disease patients with TLK and twenty cases of asymptomatic participants were recruited into this study. And the gait motion analysis was conducted. Results: The stride length was shorter in the TLK group compared to control group (1.24 ± 0.11 m vs. 1.36 ± 0.21 m, p = 0.04). Compared to control group, the stride time and step time were more prolonged in the TLK group (1.18 ± 0.11s vs. 1.11 ± 0.08 s, p = 0.03; 0.59 ± 0.06 s vs. 0.56 ± 0.04 s, p = 0.04). The gait speed of the TLK group was significantly slower than it of control group (1.05 ± 0.12 m/s vs. 1.17 ± 0.14 m/s, p = 0.01); In the sagittal plane, the range of motion (ROM) of the hip in the TLK group was significantly smaller than that of the control group (37.71 ± 4.35° vs. 40.05 ± 3.71°, p = 0.00). In the transverse plane, the adduction/abduction ROMs of the knee and ankle, as well as the internal and external rotation of the knee, were smaller in TLK group than ROMs in the control group (4.66 ± 2.21° vs. 5.61 ± 1.82°, p = 0.00; 11.48 ± 3.97° vs. 13.16 ± 5.6°, p = 0.02; 9.00 ± 5.14° vs. 12.95 ± 5.78°, p = 0.00). Discussion: The main finding of this study was that measurements of gait patterns and joint movement of the TLK group were significantly lower than those of the control group. And these impacts have the potential to exacerbate degenerative progress of joints in the lower extremities. These abnormal features of gait can also serve as a guideline for physicians to focus on TLK in these patients.

Hologenomic insights into mammalian adaptations to myrmecophagy.

Highly specialized myrmecophagy (ant- and termite-eating) has independently evolved multiple times in species of various mammalian orders and represents a textbook example of phenotypic evolutionary convergence. We explored the mechanisms involved in this unique dietary adaptation and convergence through multi-omic analyses, including analyses of host genomes and transcriptomes, as well as gut metagenomes, in combination with validating assays of key enzymes' activities, in the species of three mammalian orders (anteaters, echidnas and pangolins of the orders Xenarthra, Monotremata and Pholidota, respectively) and their relatives. We demonstrate the complex and diverse interactions between hosts and their symbiotic microbiota that have provided adaptive solutions for nutritional and detoxification challenges associated with high levels of protein and lipid metabolisms, trehalose degradation, and toxic substance detoxification. Interestingly, we also reveal their spatially complementary cooperation involved in degradation of ants' and termites' chitin exoskeletons. This study contributes new insights into the dietary evolution of mammals and the mechanisms involved in the coordination of physiological functions by animal hosts and their gut commensals.

Homeostasis of flavonoids and triterpenoids most likely modulates starch metabolism for pollen tube penetration in rice.

In angiosperms, the timely delivery of sperm cell nuclei by pollen tube (PT) to the ovule is vital for double fertilization. Penetration of PT into maternal stigma tissue is a critical step for sperm cell nuclei delivery, yet little is known about the process. Here, a male-specific and sporophytic mutant xt6, where PTs are able to germinate but unable to penetrate the stigma tissue, is reported in Oryza sativa. Through genetic study, the causative gene was identified as Chalcone synthase (OsCHS1), encoding the first enzyme in flavonoid biosynthesis. Indeed, flavonols were undetected in mutant pollen grains and PTs, indicating that the mutation abolished flavonoid biosynthesis. Nevertheless, the phenotype cannot be rescued by exogenous application of quercetin and kaempferol as reported in maize and petunia, suggesting a different mechanism exists in rice. Further analysis showed that loss of OsCHS1 function disrupted the homeostasis of flavonoid and triterpenoid metabolism and led to the accumulation of triterpenoid, which inhibits significantly α-amylase activity, amyloplast hydrolysis and monosaccharide content in xt6, these ultimately impaired tricarboxylic acid (TCA) cycle, reduced ATP content and lowered the turgor pressure as well. Our findings reveal a new mechanism that OsCHS1 modulates starch hydrolysis and glycometabolism through modulating the metabolic homeostasis of flavonoids and triterpenoids which affects α-amylase activity to maintain PT penetration in rice, which contributes to a better understanding of the function of CHS1 in crop fertility and breeding.

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study.

OBJECTIVE: To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes. PATIENTS AND METHODS: Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020. RESULTS: A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses. CONCLUSION: The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.

Diagnostic accuracy of ultrasound-based multimodal radiomics modeling for fibrosis detection in chronic kidney disease.

OBJECTIVES: To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features. METHODS: The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1-5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26-50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves. RESULTS: A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85-0.97) and 0.85 (95% CI: 0.77-0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89-0.98) and 0.83 (95% CI: 0.70-0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts). CONCLUSION: A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities. KEY POINTS: • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.

Comparison of Three-Dimensional Navigation-Guided Percutaneous Iliosacral Screw and Minimally Invasive Percutaneous Plate for the Treatment of Zone II Unstable Sacral Fractures.

OBJECTIVE: The percutaneous IS screws and the minimally invasive percutaneous plate are the most popular internal methods for Zone II unstable sacral fractures. However, the choice of fixation remains controversial for orthopaedic surgeons. The purpose of study was to evaluate and compare the clinical results of percutaneous iliosacral (IS) screw fixation under three-dimensional (3D) navigation and minimally invasive percutaneous plate fixation in the treatment of Zone II unstable sacral fractures. METHODS: A retrospective study was performed, including 64 patients with Zone II unstable sacral fractures who underwent percutaneous IS screw fixation under 3D navigation (navigation group) and minimally invasive percutaneous plate fixation (plate group) from January 2011 and March 2021 in our department. The age, gender, fracture type, mechanism of injury, injury severity score (ISS), time from admission to operation, operative time, intraoperative blood loss, hospital stay, incision length, follow-up time, time to clinical healing, and complications were recorded and analyzed. Matta standard was used to assess fracture reduction outcomes. The Majeed function system assessed functional outcomes at the last follow-up. RESULTS: The average follow-up time was (14.42 ± 1.57) months in the navigation group and (14.79 ± 1.37) months in the plate group. No statistical difference between the two groups in age, gender, fracture type, mechanism of injury, ISS, time from admission to operation, and time to clinical healing. However, significant differences were detected in operative time, intraoperative blood loss, hospital stay, and incision length (p < 0.001). According to Matta standard at 2 days postoperatively, the excellent and good rate was 91.42% in the navigation group, and it was 93.10% in the plate group. There was no significant difference between the two groups (p = 0.961). According to Majeed function system at the follow-up, the excellent and good rate was 97.14% in the navigation group, and 93.10% in the plate group. The difference between the two groups was not statistically significant (p = 0.748). There were no neurovascular injuries associated with this procedure. The incidence of complications was 44.82% (13/29) in the plate group, while 14.28% (5/35) in the navigation group (p = 0.007). CONCLUSION: This study found that compared with minimally invasive percutaneous plate fixation, percutaneous IS screw fixation under 3D navigation is a suitable option for the treatment of Zone II unstable sacral fractures. This approach is characterized by its shorter operation time, less surgical trauma, less bleeding, less hospital time, and fewer complications.

Germline gene fusions across species reveal the chromosomal instability regions and cancer susceptibility.

The canine transmissible venereal tumor (CTVT) is a clonal cell-mediated cancer with a long evolutionary history and extensive karyotype rearrangements in its genome. However, little is known about its genetic similarity to human tumors. Here, using multi-omics data we identified 11 germline gene fusions (GGFs) in CTVT, which showed higher genetic susceptibility than others. Additionally, we illustrate a mechanism of a complex gene fusion of three gene segments (HSD17B4-DMXL1-TNFAIP8) that we refer to "greedy fusion". Our findings also provided evidence that expressions of GGFs are downregulated during the tumor regressive phase, which is associated with DNA methylation level. This study presents a comprehensive landscape of gene fusions (GFs) in CTVT, which offers a valuable genetic resource for exploring potential genetic mechanisms underlying the development of cancers in both dogs and humans.