Genome-wide mapping of quantitative trait loci conferring resistance to stripe rust in spring wheat line PI 660072.

KEY MESSAGE: Two major QTL for resistance to stripe rust were mapped on chromosome 2BL and 4BL in spring wheat PI 660072, and their KASP markers were developed. Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of wheat worldwide. Identifying resistance genes is crucial for developing resistant cultivars to control the disease. Spring wheat PI 660072 (Triticum aestivum) has been identified to possess both adult-plant resistance (APR) and all-stage resistance (ASR) to stripe rust. To elucidate the genetic basis of the resistance in PI 660072, a mapping population consisting of 211 F5-F7 recombinant-inbred lines (RILs) was developed from a cross of PI 660072 with susceptible spring wheat Avocet S. The mapping population was phenotyped for stripe rust responses across five field environments from 2020 to 2022 and genotyped using the 15 K SNP (single nucleotide polymorphism) array to map stripe rust resistance loci. The mapping population was also tested at the seedling stage with predominant Chinese Pst races CYR31, CYR32, CYR34 and PST-YX1-3-1 in the greenhouse. Stripe rust resistance genes were identified using the quantitative trait locus (QTL) mapping approach. Two QTL were identified with QYrPI660072.swust-2BL mapped on the long arm of chromosome 2B for ASR and QYrPI660072.swust-4BL on the long arm of chromosome 4B for APR. To facilitate marker-assisted selection breeding, Kompetitive allele specific PCR (KASP) markers, KASP-1269 for QYrPI660072.swust-2BL and KASP-3209 for QYrPI660072.swust-4BL, were developed. These markers could be used to introgress the effective resistance QTL into new wheat cultivars.

Prevalence, treatment efficacy, and risk factors of vascular complications in acute pancreatitis: A case-control study.

OBJECTIVE: We aimed to investigate the prevalence of vascular complications in acute pancreatitis (AP), to compare patient outcomes using various treatments, and to explore the related risk factors. METHODS: Consecutive AP patients admitted from January 2010 to July 2017 were retrospectively included. Demographics, vascular complications, laboratory indices, and imaging findings were collected. Univariate and multivariate analyses were used to explore potential risk factors of vascular complications. RESULTS: Of 3048 AP patients, 808 (26.5%) had vascular complications, including visceral vein thrombosis, sinistral portal hypertension, and arterial complications. And 38 (4.7%) patients received anticoagulant therapy and had a higher rate of recanalization (P < 0.001). Bleeding occurred in 95 (11.8%) patients, who received further treatment. Multivariate analysis identified male gender (odds ratio [OR] 1.650, 95% confidence interval [CI] 1.101-2.472), hyperlipidemia (OR 1.714, 95% CI 1.356-2.165), disease recurrence (OR 3.727, 95% CI 2.713-5.118), smoking (OR 1.519, 95% CI 1.011-2.283), hemoglobin level (OR 0.987, 95% CI 0.981-0.993), white blood cell (WBC) count (OR 1.094, 95% CI 1.068-1.122), non-vascular local complications (OR 3.018, 95% CI 1.992-4.573), computed tomography severity index (CTSI) (OR 1.425, 95% CI 1.273-1.596), and acute physiology and chronic health evaluation (APACHE) II score (OR 1.057, 95% CI 1.025-1.090) were related to vascular complications. CONCLUSIONS: Vascular complications in AP is prevalent and their treatment is challenging. Further investigations are warranted to determine the optimal treatment strategy. Independent risk factors included male gender, hyperlipidemia, disease recurrence, smoking, WBC count, non-vascular local complications, CTSI, and APACHE II score.

Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

Conservative treatment of congenital radial head subluxation and non-traumatic elbow locking: A case report.

Congenital radial head subluxation is relatively rare and may be overlooked due to mild symptoms. The diagnosis mainly relies on imaging and history. Observation is an option for those with insignificant symptoms, while surgical intervention, such as ulnar osteotomy or arthroscopy, is often required when dysfunction exists. A 30-year-old man was admitted with congenital radial head dislocation, which was treated with manipulative repositioning. During follow-up, the patient regained the original mobility of the elbow joint and had no recurrence of dislocation. In conclusion, in adults with congenital dislocation of the radial head, we recommend conservative treatment as a first step.

Gibberellins regulate masculinization through the SpGAI-SpSTM module in dioecious spinach.

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA3, showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Intra-articular injection of tranexamic acid in patients with haemophilia arthritis: retrospective controlled study in total knee arthroplasty.

PURPOSE: Total knee arthroplasty is the main method for the treatment of advanced haemophilic knee arthritis. Due to the particularity of hemophilia, the blood management plan is the focus of the perioperative period for haemophilia patients. This study aimed to investigate the clinical effect and safety of intra-articular injection of tranexamic acid in patients with haemophilia. METHODS: This is a retrospective study. According to whether tranexamic acid is used or not, patients are divided into tranexamic acid group (n=30) and non-tranexamic acid group (n=29). Total blood loss, intraoperative blood loss, complete blood count, total amount of coagulation factor VIII (FVIII) usage, coagulation biomarkers, inflammatory biomarkers, knee range of motion, knee joint function, pain status, complication rate, and patient satisfaction were assessed and compared at a mean follow-up of 16 months. RESULTS: Injecting tranexamic acid into the knee joint cavity can effectively reduce the hidden blood loss and total blood loss (P<0.001), and reduce the patient's early postoperative inflammation biomarkers, pain status, and limb swelling. Therefore, the patient can obtain a better range of motion following total knee arthroplasty. In the long run, in terms of joint function and surgical satisfaction, there are no statistically significant differences. In addition, there are no statistically significant differences between the two groups of patients in terms of the total amount of FVIII usage, length of stay, and hospitalization expenses. CONCLUSION: In patients with haemophilia, intra-articular injection of tranexamic acid during total knee arthroplasty can effectively reduce postoperative blood loss, early postoperative inflammation levels, pain and limb swelling, and enable patients to receive higher-quality rehabilitation exercises to get better joint function. Previous studies on TKA in haemophilic patients have already demonstrated the efficacy of intra-articular injections of TXA in reducing postoperative blood loss. Our study confirms this efficacy.

Relationship between 25-hydroxy vitamin D and knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

Objective: In order to examine the relationship between 25-hydroxyl vitamin D and knee osteoarthritis (KOA), a meta-analysis of 8 randomized controlled trials (RCTs) publications was hereby performed. Methods: For the purpose of finding pertinent research, the databases of PubMed, Embase and the Cochrane Library were searched. Factors including tibial cartilage volume, joint space width (JSW), synovial fluid volume, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were correspondingly evaluated, and the results were expressed using SMD and 95% confidence intervals (CI). Results: The present meta-analysis evaluated the effects of vitamin D supplementation in patients with knee osteoarthritis, with 3,077 patients included. The results showed that vitamin D administration had a statistically significant impact on the amount of synovial fluid, Visual Analog Scale (VAS) and tibial cartilage. The pain and function scales of the WOMAC scale presented a statistically significant difference, and there was no discernible difference between the vitamin D and placebo groups in the stiffness scale. Additionally, bone marrow lesions and alterations in the diameter of the joint space were not influenced by the administration of vitamin D, and according to a subgroup study, a daily vitamin D supplement containing more than 2,000 IU significantly slowed the development of synovial tissue. Conclusion: Vitamin D supplementation did benefit those suffering from knee discomfort and knee dysfunction. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332033, identifier: CRD42022332033.

Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development.

Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/ + mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo-germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo-germ mice receiving fecal sample from male mice. Sex-biased gut metabolites in pseudo-germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.

Integrating massive RNA-seq data to elucidate transcriptome dynamics in Drosophila melanogaster.

The volume of ribonucleic acid (RNA)-seq data has increased exponentially, providing numerous new insights into various biological processes. However, due to significant practical challenges, such as data heterogeneity, it is still difficult to ensure the quality of these data when integrated. Although some quality control methods have been developed, sample consistency is rarely considered and these methods are susceptible to artificial factors. Here, we developed MassiveQC, an unsupervised machine learning-based approach, to automatically download and filter large-scale high-throughput data. In addition to the read quality used in other tools, MassiveQC also uses the alignment and expression quality as model features. Meanwhile, it is user-friendly since the cutoff is generated from self-reporting and is applicable to multimodal data. To explore its value, we applied MassiveQC to Drosophila RNA-seq data and generated a comprehensive transcriptome atlas across 28 tissues from embryogenesis to adulthood. We systematically characterized fly gene expression dynamics and found that genes with high expression dynamics were likely to be evolutionarily young and expressed at late developmental stages, exhibiting high nonsynonymous substitution rates and low phenotypic severity, and they were involved in simple regulatory programs. We also discovered that human and Drosophila had strong positive correlations in gene expression in orthologous organs, revealing the great potential of the Drosophila system for studying human development and disease.

Comparative transcriptomics identifies the key in planta-expressed genes of Fusarium graminearum during infection of wheat varieties.

Fusarium head blight (FHB), caused mainly by the fungus Fusarium graminearum, is one of the most devastating diseases in wheat, which reduces the yield and quality of grain. Fusarium graminearum infection of wheat cells triggers dynamic changes of gene expression in both F. graminearum and wheat, leading to molecular interactions between pathogen and host. The wheat plant in turn activates immune signaling or host defense pathways against FHB. However, the mechanisms by which F. graminearum infects wheat varieties with different levels of host resistance are largely limited. In this study, we conducted a comparative analysis of the F. graminearum transcriptome in planta during the infection of susceptible and resistant wheat varieties at three timepoints. A total of 6,106 F. graminearum genes including those functioning in cell wall degradation, synthesis of secondary metabolites, virulence, and pathogenicity were identified during the infection of different hosts, which were regulated by hosts with different genetic backgrounds. Genes enriched with metabolism of host cell wall components and defense response processes were specifically dynamic during the infection with different hosts. Our study also identified F. graminearum genes that were specifically suppressed by signals derived from the resistant plant host. These genes may represent direct targets of the plant defense against infection by this fungus. Briefly, we generated databases of in planta-expressed genes of F. graminearum during infection of two different FHB resistance level wheat varieties, highlighted their dynamic expression patterns and functions of virulence, invasion, defense response, metabolism, and effector signaling, providing valuable insight into the interactions between F. graminearum and susceptible/resistant wheat varieties.

Hydroxycamptothecin regulates scar formation of the filtration channel under scleral flap by inhibiting the proliferation of scleral fibroblasts.

BACKGROUND: To investigate the inhibitory effect of a hyaluronic acid hydrogel loaded with hydroxycamptothecin (HCPT) on scar formation after filtration surgery in a rabbit model. METHODS: Scleral fibroblasts were isolated and extracted from rabbits' eyes. After treatment with different concentrations of HCPT, cytotoxicity was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and proliferation and extent of apoptosis were analysed using flow cytometry. Hydrogels loaded with different dosages of HCPT were prepared and placed under the scleral flap after the filtration surgery. One day, one week, and two weeks after surgery, follicular, conjunctival, corneal, and anterior chamber inflammation and iris and lens changes were observed. RESULTS: In vitro, compared with cells not treated with HCPT, cells treated with HCPT had decreased survival rate and proliferation, and the apoptosis level increased with increasing HCPT concentrations (p < 0.05). In vivo, the flattening time of filtering blebs in the three groups treated with different dosages of HCPT hydrogel was delayed. The degrees of oedema, inflammation, and bleeding were similar to those observed in the control group. The HCPT hydrogel effectively downregulated the expression of collagen 1 and 3 and tissue inhibitor of metalloproteinase 2 and upregulated the expression of matrix metalloproteinase 2 in a dose-dependent manner. CONCLUSIONS: HCPT significantly inhibited the growth of rabbits' scleral fibroblasts and effectively inhibited scar formation after filtering surgery by accelerating the degradation of extracellular matrix deposition.

Explore the effects of forest travel activities on university students' stress affection.

This study aims to explore the effects of forest travel activities on university students' stress affection. Forty volunteer university students participated in this study. All participants were asked to complete physiological (Heart Rate Variability) and psychological (Brief Profile of Mood State and State-Trait Anxiety Inventory) tests before and after the travel activities. The results reported that students' heart rates were significantly lower after the forest travel activities than before. All domains of negative mood and anxiety decreased from the pre-test to the post-test. This study found that university students could feel less stressed if they went on forest travel activities.

Total knee arthroplasty in Ranawat II valgus deformity with enlarged femoral valgus cut angle: A new technique to achieve balanced gap.

BACKGROUND: Nearly 10% of patients undergoing primary total knee arthroplasty (TKA) have valgus deformity (VD) of the knee. For severe VD of the knee, a more lateral structural release is needed to achieve balance between medial and lateral space and neutral femorotibial mechanical axis (FTMA), which is challenging and technical. AIM: To introduce a new surgical technique of resection, soft tissue release, and FTMA for Ranawat type-II VD with a 5-year follow-up. METHODS: A retrospective study was conducted on patients who underwent TKA from December 2011 to December 2014. Hip-knee-ankle (HKA), range of motion (ROM), Oxford knee score (OKS), and knee society score (KSS) were used to assess the joint activity of patients in the new theory TKA group (NT-TKA) and were compared with those of the conventional TKA group (C-TKA). RESULTS: A total of 103 people (103 knees) were included in this study, including 42 patients with an average follow-up period of 83 mo in the C-TKA group and 61 patients with an average follow-up period of 76 mo in the NT-TKA group. Six patients had constrained prosthesis, one had common peroneal nerve injury, and two had joint instability in the C-TKA group, but none of these occurred in the NT-TKA group. There were significant statistical differences in constrained prosthesis usage and complications between the groups (P = 0.002 and P = 0.034, respectively). The KSS at 1 mo post-operation for the C-TKA and NT-TKA groups were 11.2 ± 3.8 and 13.3 ± 2.9, respectively, with a significant difference (P = 0.007). However, the data of HKA, ROM, OKS KSS, and prosthesis survival rate were insignificant (P > 0.05) in both the preoperative and follow-up periods. CONCLUSION: Adopting 5°-7° valgus cut angle for VD and sacrificing 2° neutral FTMA for severe VD which cannot be completely corrected during TKA can reduce the need for soft tissue release, maintain early joint stability, reduce the use of constrained prostheses, and minimize postoperative complications.

Bilateral synchronous total hip arthroplasty for end-stage arthropathy in hemophilia A patients: A retrospective study.

Total hip arthroplasty (THA) has been an effective tool of advanced hemophiliac hip arthritis. There are only limited data of bilateral synchronous THA for end-stage arthropathy in hemophilia A patients. The aim of this retrospective study was to analyze clinical outcome and complication rate of bilateral THA for hemophilia A patients with end-stage arthropathy of hip and review the operative strategy. From August 2012 to July 2016, 48 hips of 24 patients with hemophilia A patients underwent THA by a single experienced chief orthopedic surgeon. Clinical and radiological evaluations were included of operation time, blood loss, the quantity of blood transfusion, clotting factor consumption, duration of hospitalization, modified Harris hip score, complication rate, and radiographic assessment. All the 24 patients successfully completed the operation, followed up for 5 to 8 years, and the mean time was 6.5 years. The average operation time was 140 minutes (range, 120-180 minutes). The average total blood loss was 225 mL (range, 150-400 mL). The mean red blood cell transfusion amount was 2.4 U (range, 0-6 U). the mean hospitalization time was 24 days (range, 16-46 days). The mean amount of clotting factor VIII used in the perioperative period for management of hemophilia A was 30,600 U (range, 18,000-52,000 U). Average modified Harris hip score increased from 46.6 (range 28-70) points preoperatively to 90.2 (range 75-98) points at final follow-up, complications were few. With excellent operative techniques and hematological management, bilateral synchronous THA for end-stage arthropathy in hemophilia A patients can provide satisfactory outcomes.

Hidden blood loss of total knee arthroplasty in hemophilia arthritis: an analysis of influencing factors.

BACKGROUND: Total knee arthroplasty is the leading way to treat hemophilia arthritis. At present, there is a lack of research on the influencing factors of blood loss in total knee arthroplasty for hemophilia arthritis. This study comprehensively explores the definite factors affecting the hidden blood loss in total knee arthroplasty for hemophilia patients. MATERIALS AND METHODS: Ninety-two hemophilia A patients who underwent total knee arthroplasty in our center were included. Demographics, laboratory data, surgical data, and complications were collected. The Gross equation and Sehat equation were used to calculate the estimated value of hidden blood loss. Multivariate linear regression analysis was used to determine the influencing factors of hidden blood loss. RESULT: The hidden blood loss of hemophilia A patients undergoing total knee arthroplasty was 1069.51 ± 341.99 mL, and the age was positively correlated with the hidden blood loss (P < 0.001), while tranexamic acid, FVIII prophylaxis, and incremental invivo recovery were negatively correlated with the hidden blood loss (P < 0.001, P = 0.008, P = 0.017). CONCLUSION: Elderly patients have a greater risk of blood loss, and additional preventive measures can be appropriately added. Intraoperative intra-articular injection of tranexamic acid is recommended to reduce hidden blood loss, FVIII prophylaxis is recommended for every patient. We recommend that all HA patients measure the incremental invivo recovery and develop a personalized infusion regimen of coagulation factor.

Effects of Elevated CO2 on the Fitness of Three Successive Generations of Lipaphis erysimi.

To assess the effect of elevated CO2 on the development, fecundity, and population dynamic parameters of L. erysimi, the age-stage, two-sex life table was used to predict the individual fitness and population parameters of three successive generations of L. erysimi in this study. The results show that a significantly longer total pre-adult stage before oviposition (TPOP) was observed in the third generation compared with the first generation of L. erysimi under the 800 µL/L CO2 treatment. The fecundity is significantly lower in the 800 µL/L CO2 treatment than that in the 400 µL/L CO2 treatment in the third generation of L. erysimi, which indicates that elevated CO2 had a negative effect on the individual fitness parameters of L. erysimi. Additionally, the life expectancy (exj) is significantly lower under the 800 µL/L CO2 treatment than that under the 400 µL/L CO2 treatment in the three successive generations. A significantly higher intrinsic rate of increase (r) and finite rate of increase (λ) were found in the second generation compared with those in the first and third generations of L. erysimi under the 800 µL/L CO2 treatment. Moreover, significantly lower r and λ were observed under the 800 µL/L CO2 treatment compared with those under the 400 µL/L and 600 µL/L CO2 treatments in the first generation of L. erysimi, which indicates that elevated CO2 has a short-term effect on the population parameters (r and λ) of L. erysimi. Our experiment can provide the data for the comprehensive prevention and control of L. erysimi in the future with increasing CO2 levels.

Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. Design, Settings, and Participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). Conclusions and Relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02578069.

Total knee arthroplasty and femoral osteotomy with a patient-specific cutting guide to treat haemophilic arthritis with severe extra-articular deformity: A case report and review of literatures.

Background: Total knee arthroplasty (TKA) is recommended for haemophilic patients with end-stage arthritis. TKA combined with a one-stage extraarticular osteotomy is uncommon in the treatment of haemophilic arthritis (HA) with severe extra-articular deformities (EADs) and a history of inhibitors under the guidance of a patient-specific cutting guide (PSI). Case presentation: We reported a 20-year-old male patient with severe haemophilia, limited knee functionality, a 30° sagittal deformity on the femoral side and a history of inhibitors. We adopted the Van Creveld protocol to decrease the inhibitors. TKA and extra-articular osteotomy (EAO) were performed simultaneously and sequentially under the guidance of PSI. An appropriate central alignment of the lower limb was restored by using cement prostheses with antibiotics and femur shaft locking compression plates. The last follow-up showed that the knee function was good, the VAS score was 0, the WOMAC score was 18 and the ROM was 0°-95°. Conclision: Regular haematology management can reduce the perioperative bleeding risk in haemophilic patients treated with inhibitors. PSI plays an important role in guiding the TKA and EAO of end-stage HA patients with severe EAD.

Mutational analysis of mitochondrial tRNA genes in 138 patients with Leber's hereditary optic neuropathy.

INTRODUCTION: Mutations in mitochondrial DNA (mtDNA) are the most important causes for Leber's hereditary optic neuropathy (LHON). Of these, three primary mtDNA mutations account for more than 90% cases of this disease. However, to date, little is known regarding the relationship between mitochondrial tRNA (mt-tRNA) variants and LHON. AIM: In this study, we aimed to investigate the association between mt-tRNA variants and LHON. METHODOLOGY: One hundred thirty-eight LHON patients lacking three primary mutations (ND1 3460G > A, ND4 11778Gxs > A, and ND6 14484 T > C), as well as 266 controls were enrolled in this study. PCR-Sanger sequencing was performed to screen the mt-tRNA variants. Moreover, the phylogenetic analysis, pathogenicity scoring system, as well as mitochondrial functions were performed. RESULTS: We identified 8 possible pathogenic variants: tRNAPhe 593 T > C, tRNALeu(UUR) 3275C > T, tRNAGln 4363 T > C, tRNAMet 4435A > G, tRNAAla 5587 T > C, tRNAGlu 14693A > G, tRNAThr 15927G > A, and 15951A > G, which may change the structural and functional impact on the corresponding tRNAs, and subsequently lead to a failure in tRNA metabolism. Furthermore, significant reductions in mitochondrial ATP and MMP levels and an overproduction of ROS were observed in cybrid cells containing these mt-tRNA variants, suggesting that these variants may lead to mitochondrial dysfunction which was responsible for LHON. CONCLUSION: Our study indicated that mt-tRNA variants were associated with LHON, and screening for mt-tRNA variants were recommended for early detection, diagnosis, and prevention of maternally inherited LHON.