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1.
Int J Pharm ; : 124676, 2024 Sep 08.
Article in English | MEDLINE | ID: mdl-39255876

ABSTRACT

Over the last 15 years, a small number of paediatric artemisinin-based combination therapy products have been marketed. These included Riamet® and Coartem® dispersible tablets, a combination of artemether and lumefantrine, co-developed by the Medicines for Malaria Venture and Novartis. Disappointingly, patient compliance, requirement for high-fat meal, and sporadic drug dissolution behaviours following administration still result in considerable challenges for these products. The first and foremost barrier that needs addressed for successful delivery of the artemether/lumefantrine combination is the poor solubility of lumefantrine within the gastrointestinal fluids. In this work, amorphous solid dispersions of lumefantrine within Soluplus®-based matrices have been manufactured using hot melt extrusion as a potential formulation strategy to achieve enhanced dissolution and apparent solubility. The drug loading capacity of Soluplus® to accommodate amorphous lumefantrine, whilst ensuring improved in-vitro dissolution performance, was investigated. The extrusion process employed a variety of processing parameters, including various temperature profiles and different production scales. The influence of variation in extrusion conditions upon the physical stability of manufactured amorphous solid dispersions was also examined. This allowed for a greater understanding of the role of extrusion processing conditions on the performance of supersaturated amorphous solid dispersions during dissolution and storage. This may allow for the design and manufacture of drug enabled formulations with lower drug dosing and thus a lower risk of adverse effects.

2.
J Med Chem ; 67(18): 16018-16034, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39269788

ABSTRACT

TSHR is a member of the glycoprotein hormone receptors, a subfamily of class A G-protein-coupled receptors and plays pivotal roles in various physiological and pathological processes, particularly in thyroid growth and hormone production. The aberrant TSHR function has been implicated in several human diseases including Graves' disease and orbitopathy, nonautoimmune hyperthyroidism, hypothyroidism, cancer, neurological disorders, and osteoporosis. Consequently, TSHR is recognized as an attractive therapeutic target, and targeting TSHR with small-molecule modulators including agonists, antagonists, and inverse agonists offers great potential for drug discovery. In this perspective, we summarize the structures and biological functions of TSHR as well as the recent advances in the development of small-molecule TSHR modulators, highlighting their chemotypes, mode of actions, structure-activity relationships, characterizations, in vitro/in vivo activities, and therapeutic potential. The challenges, new opportunities, and future directions in this area are also discussed.


Subject(s)
Receptors, Thyrotropin , Small Molecule Libraries , Humans , Receptors, Thyrotropin/metabolism , Receptors, Thyrotropin/antagonists & inhibitors , Structure-Activity Relationship , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Small Molecule Libraries/therapeutic use , Animals , Drug Discovery
3.
Nat Cell Biol ; 26(9): 1597-1612, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39147874

ABSTRACT

Bone metastasis is a lethal consequence of breast cancer. Here we used single-cell transcriptomics to investigate the molecular mechanisms underlying bone metastasis colonization-the rate-limiting step in the metastatic cascade. We identified that lymphotoxin-ß (LTß) is highly expressed in tumour cells within the bone microenvironment and this expression is associated with poor bone metastasis-free survival. LTß promotes tumour cell colonization and outgrowth in multiple breast cancer models. Mechanistically, tumour-derived LTß activates osteoblasts through nuclear factor-κB2 signalling to secrete CCL2/5, which facilitates tumour cell adhesion to osteoblasts and accelerates osteoclastogenesis, leading to bone metastasis progression. Blocking LTß signalling with a decoy receptor significantly suppressed bone metastasis in vivo, whereas clinical sample analysis revealed significantly higher LTß expression in bone metastases than in primary tumours. Our findings highlight LTß as a bone niche-induced factor that promotes tumour cell colonization and osteolytic outgrowth and underscore its potential as a therapeutic target for patients with bone metastatic disease.


Subject(s)
Bone Neoplasms , Breast Neoplasms , Lymphotoxin-beta , Osteoblasts , Osteolysis , Bone Neoplasms/secondary , Bone Neoplasms/metabolism , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Female , Animals , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Humans , Osteolysis/metabolism , Osteolysis/pathology , Osteolysis/genetics , Osteoblasts/metabolism , Osteoblasts/pathology , Cell Line, Tumor , Lymphotoxin-beta/metabolism , Lymphotoxin-beta/genetics , Mice , Tumor Microenvironment , Signal Transduction , Osteogenesis/genetics , Osteoclasts/metabolism , Osteoclasts/pathology , Gene Expression Regulation, Neoplastic , Cell Adhesion
4.
Animals (Basel) ; 14(15)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39123678

ABSTRACT

The types and morphology of sheep horns have been extensively researched, yet the genetic foundation underlying the emergence of diverse horn characteristics during the breeding of polled Tibetan sheep has remained elusive. Genome-wide association analysis (GWAS) was performed on 103 subtypes (normal large horn, scurs, and polled) differentiated from G2 (offspring (G2) of parent (G1) of polled) of the polled core herd. Six single nucleotide polymorphisms (SNPs) located on chromosome 10 of the relaxin family peptide receptor 2 (RXFP2) gene exhibited positive correlations with horn length, horn base circumference, and horn base interval. Furthermore, in genotyping 382 G2 individuals, significant variations were observed for each specific horn type. Three additional mutations were identified near the target SNP upstream of the amplification product. Finally, the RXFP2-specific haplotype associated with the horned trait effectively maintained horn length, horn base circumference, and horn base interval in Tibetan sheep, as confirmed by population validation of nine loci in a sample size of 1125 individuals. The present study offers novel insights into the genetic differentiation of the horned type during improvement breeding and evolution, thereby establishing a robust theoretical foundation for polled Tibetan sheep breeding and providing valuable guidance for practical production.

5.
Chem Sci ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39156933

ABSTRACT

The asymmetric synthesis of thiophene-derived compounds, including catalytic asymmetric dearomatization of thiophene and atroposelective synthesis of benzothiophene derivatives, has rarely been reported. In this work, the asymmetric transformation of the thiophene motif is investigated. Through the rational design of substrates with a thiophene structure, by using the vinylidene ortho-quinone methide (VQM) intermediate as a versatile tool, axially chiral naphthyl-benzothiophene derivatives and thiophene-dearomatized chiral spiranes were obtained in high yields with excellent enantioselectivities.

6.
Genes (Basel) ; 15(7)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39062700

ABSTRACT

Tibetan sheep are vital to the ecosystem and livelihood of the Tibetan Plateau; however, traditional breeding methods limit their production and growth. Modern molecular breeding techniques are required to improve these traits. This study identified a single nucleotide polymorphism (SNP) in myostatin (MSTN) and Callipyge in Tibetan sheep. The findings indicated notable associations between MSTN genotypes and growth traits including birth weight (BW), body length (BL), chest width (ChW), and chest circumference (ChC), as well as a particularly strong association with cannon circumference (CaC) at 2 months of age. Conversely, Callipyge polymorphisms did not have a significant impact on Tibetan sheep. Moreover, the analyses revealed a significant association between sex and BW or hip width (HW) at 2 months of age and ChW, ChC, and CaC at 4 months of age. Furthermore, the study's results suggested that the genotype of MSTN as a GA was associated with a notable sex effect on BW, while the genotype of Callipyge (CC) showed a significant impact of sex on CaC at 2 months of age. These results indicated that the SNP of MSTN could potentially serve as a molecular marker for early growth traits in Tibetan sheep.


Subject(s)
Myostatin , Polymorphism, Single Nucleotide , Animals , Myostatin/genetics , Sheep/genetics , Sheep/growth & development , Female , Male , Tibet , Genotype , Phenotype , Birth Weight/genetics , Breeding
7.
Arch Microbiol ; 206(8): 352, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012499

ABSTRACT

Tuberculosis (TB) is one of the infectious diseases caused by the pathogen Mycobacterium tuberculosis that continuously threatens the global human health. Bacillus Calmette-Guérin (BCG) vaccine is the only vaccine that has been used clinically to prevent tuberculosis in recent centuries, but its limitations in preventing latent infection and reactivation of tuberculosis do not provide full protection. In this study, we selected the membrane-associated antigen Rv1513 of Mycobacterium. In order to achieve stable expression and function of the target gene, the prokaryotic expression recombinant vector pET30b-Rv1513 was constructed and expressed and purified its protein. Detection of IFN- γ levels in the peripheral blood of TB patients stimulated by whole blood interferon release assay (WBIA) and multi-microsphere flow immunofluorescence luminescence (MFCIA) revealed that the induced production of cytokines, such as IFN-γ and IL-6, was significantly higher than that in the healthy group. Rv1513 combined with adjuvant DMT (adjuvant system liposomes containing dimethyldioctadecylammonium bromide (DDA), monophospholipid A (MPL), and trehalose-660-dibenzoic acid (TDB)) was used to detect serum specific antibodies, cytokine secretion from splenic suprasplenic cell supernatants, and multifunctional T-cell levels in splenocytes in immunised mice. The levels of IFN-γ, TNF-α, and IL-2 secreted by mouse splenocytes were found in the Rv1513+DMT group and the BCG+Rv1513+DMT group. The serum levels of IgG and its subclasses and the number of IFN-γ+T cells, TNF-α+T and IFN-γ+TNF-α+T cells in the induced CD4+/CD8+T cells in mice were significantly higher than those in the BCG group, and the highest levels were found in the BCG+Rv1513+DMT group. These findings suggest that Rv1513/DMT may serve as a potential subunit vaccine candidate that may be effective as a booster vaccine after the first BCG vaccination.


Subject(s)
Mycobacterium tuberculosis , Th1 Cells , Tuberculosis Vaccines , Tuberculosis , Animals , Mycobacterium tuberculosis/immunology , Mycobacterium tuberculosis/genetics , Mice , Humans , Th1 Cells/immunology , Tuberculosis Vaccines/immunology , Tuberculosis Vaccines/genetics , Tuberculosis Vaccines/administration & dosage , Tuberculosis/immunology , Tuberculosis/prevention & control , Tuberculosis/microbiology , Female , Antigens, Bacterial/immunology , Antigens, Bacterial/genetics , Cytokines/metabolism , Cytokines/immunology , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Interferon-gamma/immunology , Interferon-gamma/metabolism , Mice, Inbred BALB C , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Adjuvants, Immunologic/administration & dosage , Adult
8.
Nat Mater ; 23(7): 866-868, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38956347
9.
BMC Musculoskelet Disord ; 25(1): 459, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858713

ABSTRACT

PURPOSE: The risk factors for excessive blood loss and transfusion during total knee arthroplasty (TKA) remain unclear. The present study aimed to determine the risk factors for excessive blood loss and establish a predictive model for postoperative blood transfusion. METHODS: This retrospective study included 329 patients received TKA, who were randomly assigned to a training set (n = 229) or a test set (n = 100). Univariate and multivariate linear regression analyses were used to determine risk factors for excessive blood loss. Univariate and multivariate logistic regression analyses were used to determine risk factors for blood transfusion. R software was used to establish the prediction model. The accuracy and stability of the models were evaluated using calibration curves, consistency indices, and receiver operating characteristic (ROC) curve analysis. RESULTS: Risk factors for excessive blood loss included timing of using a tourniquet, the use of drainage, preoperative ESR, fibrinogen, HCT, ALB, and free fatty acid levels. Predictors in the nomogram included timing of using a tourniquet, the use of drainage, the use of TXA, preoperative ESR, HCT, and albumin levels. The area under the ROC curve was 0.855 (95% CI, 0.800 to 0.910) for the training set and 0.824 (95% CI, 0.740 to 0.909) for the test set. The consistency index values for the training and test sets were 0.855 and 0.824, respectively. CONCLUSIONS: Risk factors for excessive blood loss during and after TKA were determined, and a satisfactory and reliable nomogram model was designed to predict the risk for postoperative blood transfusion.


Subject(s)
Arthroplasty, Replacement, Knee , Blood Loss, Surgical , Blood Transfusion , Nomograms , Humans , Arthroplasty, Replacement, Knee/adverse effects , Female , Male , Retrospective Studies , Risk Factors , Middle Aged , Aged , Blood Transfusion/statistics & numerical data , Risk Assessment , Predictive Value of Tests
10.
J Orthop Traumatol ; 25(1): 33, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926175

ABSTRACT

BACKGROUND: The effectiveness of robot-assisted surgery remains contentious due to the lack of high-quality randomized controlled trials (RCTs) to elevate the level of evidence. We aimed to evaluate the postoperative radiographic outcomes of robot-assisted (RAS-THA) versus manual (M-THA) total hip arthroplasty. METHODS: This multicenter RCT was performed from March 1, 2021 to December 1, 2021. Patients were randomly assigned to routine M-THA or to RAS-THA that used the TRex-RS orthopedic joint surgical navigation system. The primary outcome was to compare the acetabular component orientation, femoral stem alignment, femoral canal fill ratio, and leg length discrepancy between RAS-THA and M-THA using postoperative radiography. Subgroup analyses of the two groups stratified by surgical approach, gender, and BMI were also conducted. RESULTS: Seventy-three participants were randomly allocated to the RAS-THA group, while seventy-two participants were assigned to the M-THA group. Compared to the M-THA group, the RAS-THA group exhibited less variability in the preoperative planning of the vertical center of rotation (VCOR; P < 0.001), demonstrated a significant advantage in femoral stem alignment (P = 0.004), and showed pronounced decreases in inequality and in the variability in leg length discrepancy (P < 0.001). There was no significant difference in the Lewinnek safe-zone ratio (P = 0.081) and the femoral canal fill ratio (P > 0.05) between the two groups. Further subgroup analysis also showed that the RAS-THA group had fewer horizontal center of rotation (HCOR) and leg length differences when stratified by surgical approach, gender, and overweight status. CONCLUSION: This RCT found that, regardless of the surgical approach, gender, or body mass index, RAS-THA can effectively improve the postoperative VCOR and significantly reduce the variability of leg length difference. RAS-THA should be considered an effective method to enhance surgical precision by achieving less variability in challenging patients with leg length discrepancies. TRIAL REGISTRATION: ChiCTR2100044124.


Subject(s)
Arthroplasty, Replacement, Hip , Robotic Surgical Procedures , Humans , Male , Female , Arthroplasty, Replacement, Hip/methods , Robotic Surgical Procedures/methods , Middle Aged , Aged , Radiography , Leg Length Inequality/surgery , Leg Length Inequality/diagnostic imaging , Leg Length Inequality/etiology , Treatment Outcome
11.
Pediatr Rheumatol Online J ; 22(1): 51, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724970

ABSTRACT

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies. METHODS: In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes. RESULTS: Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors-kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10- 6) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)-and three protective factors-3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14-0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20-0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51-0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA. CONCLUSION: Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.


Subject(s)
Arthritis, Juvenile , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Arthritis, Juvenile/genetics , Arthritis, Juvenile/blood , Mendelian Randomization Analysis/methods , Child , Polymorphism, Single Nucleotide , Kynurenine/blood , Kynurenine/analogs & derivatives
12.
J Robot Surg ; 18(1): 79, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38365906

ABSTRACT

Postoperative complications due to inaccurate prosthesis positioning are the main causes of early revision. The aim of this study was to (1) determine whether novel designed whole-process robotic assisted hip system allowed better radiographic outcomes and lower complications risk on the femoral side particularly stem subsidence compared to conventional THA, and to (2) identify the comparison of early clinical outcomes. 72 patients were initially enrolled and randomly divided into 2 groups. Finally, only 65 patients (31 RA-THAs, 34 C-THAs) were analyzed who had full 18-month follow-up data. Radiographic follow-up was performed at immediate and 6-month postoperatively, while clinical follow-up at 18-month postoperatively. Stem-related radiographic outcomes, femoral side complications and clinical scores were compared. The robotic arm allowed better radiographic outcomes of the femoral side, including a higher canal fill ratio (CFR) at B1 (P = 0.040), more neutral stem alignment (P = 0.029), lower subsidence (P = 0.023) and lower leg length discrepancy (LLD) (P = 0.010). In addition, low CFR at B1 (P = 0.001) was found the risk factor for subsidence. However, early clinical outcomes were consistent between both groups. The novel designed whole-process robotic assisted hip system covers both femoral and acetabular side operations. It allows accurate and safe manipulation of femoral side, including better stem-related radiographic outcomes and lower risk of subsidence and LLD. However, no advantage of robotic system in early clinical score was identified. Clinical trial registration number: ChiCTR2100044124.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Robotic Surgical Procedures , Humans , Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Robotic Surgical Procedures/methods , Prospective Studies , Treatment Outcome , Retrospective Studies
13.
Int J Surg ; 110(4): 2141-2150, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38241325

ABSTRACT

OBJECTIVE: To compare the effect of a new complete robot-assisted total hip arthroplasty (RA-THA) with that of the manual total hip arthroplasty (MTHA) and to verify the accuracy and safety of the former. METHODS: Overall, 148 patients were enroled from 3 March 2021 to 28 December 2021 in this study and classified into RA-THA ( n =74 patients) and MTHA ( n =74 patients) groups. The sex, age, operative side, BMI, diagnosis, other basic information, operative time, acetabular prosthesis anteversion and inclination, femoral prosthesis anteversion and angulation, femoral prosthesis filling rate, leg length discrepancy (LLD), Harris hip score, and visual analogue scale (VAS) score of the two groups were compared. RESULTS: No significant differences were observed in the two groups regarding sex, age, operative side, BMI, diagnosis, Harris hip score, VAS score, acetabular inclination, acetabular prosthesis anteversion, femoral prosthesis anteversion, combined anteversion, and femoral prosthesis filling rate ( P >0.05). The operative time was significantly longer in the RA-THA group than in the MTHA group (106.71±25.22 min vs. 79.42±16.16 min; t=7.30, P <0.05). The femoral angulation (1.78°±0.64°) and LLD (2.87±1.55 mm) in the RA-THA group were significantly lesser than those in the MTHA group (2.22°±1.11° and 5.81±6.27 mm, respectively; t=-2.95 and t=-3.88, P <0.05). CONCLUSION: The complete RA-THA has some advantages over the traditional procedure in restoring the lower limb length and controlling the femoral prosthesis angulation. Thus, this study verifies the accuracy and safety of the robot-assisted system.


Subject(s)
Arthroplasty, Replacement, Hip , Robotic Surgical Procedures , Humans , Male , Female , Arthroplasty, Replacement, Hip/methods , Arthroplasty, Replacement, Hip/instrumentation , Robotic Surgical Procedures/methods , Middle Aged , Aged , Operative Time , Treatment Outcome , Hip Prosthesis
14.
Tuberculosis (Edinb) ; 145: 102480, 2024 03.
Article in English | MEDLINE | ID: mdl-38278100

ABSTRACT

Tuberculosis (TB) today remains the leading cause of global deaths due to infectious bacterial pathogens. The Bacillus Calmette-Guérin (BCG) vaccine is the only vaccine clinically used to prevent TB. However, its limitations in preventing latent infection and TB reactivation mean that it does not provide comprehensive protection. In this study, we successfully constructed and expressed the multistage fusion protein, SHR3, and used whole blood IFN-γ release assay (WBIA) with flow cytometry to detect antigen specificity, further confirmed by enzyme-linked immunosorbent assay (ELISA). SHR3 and its subfractional proteins stimulated the level of IFN-γ production by lymphocytes from M. tb-infected patients, inducing the production of single-positive and double-positive CD4+ and CD8+ T cells with IFN-γ and IL-2, at levels significantly higher than those of healthy controls. The fusion protein and complex adjuvant group (SHR3/DMT) induced mice to produce significantly higher levels of IgG antibodies and their subclasses, with IgG2a/IgG1 results showing a convergent Th1-type response; mice in the BCG + SHR3/DMT group induced secretion of the highest levels of IL-2, and TNF-α, irrespective of stimulation with purified protein derivative or SHR3. These findings suggest that SHR3/DMT could be a potential subunit vaccine candidate that may serve as an effective booster vaccine after BCG primary immunization.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis Vaccines , Tuberculosis , Humans , Animals , Mice , BCG Vaccine , CD8-Positive T-Lymphocytes , Interleukin-2/metabolism , Antigens, Bacterial/genetics , Tuberculosis/prevention & control , Adjuvants, Immunologic , Bacterial Proteins/genetics
15.
J Orthop Surg Res ; 18(1): 830, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37924147

ABSTRACT

BACKGROUND: To investigate the accuracy and safety of a newly constructed robotic arm which can cover the whole process of THA, we performed a series of robot-assisted total hip replacement on the cadaver. METHODS: Fifteen frozen cadaveric specimens (30 hips) were used for this study. In this investigation, united hip system and Longwell robotic-assisted system were used. The entire lower limb was CT scanned prior to surgery. The 3D model was produced based on CT data; the site of the prosthesis, including acetabular anteversion, inclination angle, and the position of femoral prosthesis, was planned. With the assistance of a robotic arm, the surgeon changed the parameters based on the preoperative plan and the actual condition during surgery, and completed the whole procedure. Following surgery, we measured the acetabular anteversion angle, acetabular inclination angle, femur anteversion angle, combined anteversion angle, stem angulation, and canal fill ratio. RESULTS: The parameters proved that the acetabular anteversion angle was 16.85 ± 3.00°, the acetabular inclination angle was 40.38 ± 5.37°, femur anteversion angle was 15.90 ± 9.01°, combined anteversion angle was 32.75 ± 9.03°, stem angulation was 1.84 ± 0.99°, and leg length discrepancy was 2.47 ± 1.43 mm. The canal fill ratio (CFR) of femoral prosthesis of osteotomy line in sagittal section is 99.72 ± 1.54% and in coronal section is 62.94 ± 8.91%; below osteotomy line 2.5 cm in sagittal section is 100.00% and in coronal section is 81.48 ± 12.94%; below osteotomy line 7.5 cm in sagittal section is 59.51 ± 12.94% and in coronal section is 89.79 ± 11.13%; femoral shaft isthmus in sagittal section is 56.41 ± 13.80% and in coronal section is 84.95 ± 15.17%. CONCLUSION: The accuracy and safety of this novel robotic arm are suitable for preparing both the acetabular and femoral sides, providing evidence for clinical trial.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Robotic Surgical Procedures , Humans , Arthroplasty, Replacement, Hip/methods , Tomography, X-Ray Computed/methods , Acetabulum/diagnostic imaging , Acetabulum/surgery , Femur/diagnostic imaging , Femur/surgery , Cadaver
16.
Sci Rep ; 13(1): 17283, 2023 10 12.
Article in English | MEDLINE | ID: mdl-37828092

ABSTRACT

Copy number variation (CNV) is a genetic structural polymorphism important for phenotypic diversity and important economic traits of livestock breeds, and it plays an important role in the desired genetic variation. This study used whole genome sequencing to detect the CNV variation in the genome of 6 local Tibetan sheep groups. We detected 69,166 CNV events and 7230 copy number variable regions (CNVRs) after merging the overlapping CNVs, accounting for 2.72% of the reference genome. The CNVR length detected ranged from 1.1 to 1693.5 Kb, with a total length of 118.69 Mb and an average length of 16.42 Kb per CNVR. Functional GO cluster analysis showed that the CNVR genes were mainly involved in sensory perception systems, response to stimulus, and signal transduction. Through CNVR-based Vst analysis, we found that the CACNA2D3 and CTBP1 genes related to hypoxia adaptation, the HTR1A gene related to coat color, and the TRNAS-GGA and PIK3C3 genes related to body weight were all strongly selected. The findings of our study will contribute novel insights into the genetic structural variation underlying hypoxia adaptation and economically important traits in Tibetan sheep.


Subject(s)
DNA Copy Number Variations , Multifactorial Inheritance , Animals , Sheep/genetics , Tibet , Genome/genetics , Hypoxia/genetics , Polymorphism, Single Nucleotide
17.
Front Surg ; 10: 1237075, 2023.
Article in English | MEDLINE | ID: mdl-37795146

ABSTRACT

Total hip revision with osseous defects can be very difficult. Artificial intelligence offers preoperative planning, real-time measurement, and intraoperative judgment, which can guide prothesis placement more accurately. Three-dimensional printed metel augment modules which are made according to the individualized osseous anatomy, can fit the osseous defects well and provide mechanical support. In this case, we used AI to plan the size and position of the acetabular cup and 3D-printed augmented modules in a complicated hip revision with an acetabular bone defects, which achieved stable fixation and relieved hip pain postoperatively.

18.
Front Med (Lausanne) ; 10: 1212580, 2023.
Article in English | MEDLINE | ID: mdl-37795417

ABSTRACT

Ochronosis is a rare autosomal recessive disorder of tyrosine metabolism characterized by multilevel spinal degeneration and arthritis of large weight-bearing joints, which is referred to as ochronotic arthropathy. In this case report, we describe diagnosis and treatment of ochronotic arthropathy in a patient who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA). The Harris hip score was 26 preoperatively and 45, 68, 76, 90, 92, and 94 at 1, 3, 6, 9, 11, and 14 months, respectively, postoperatively. The forgotten joint score (FJS) of the hip was 27.8, 52.8, 81.1, 89.0, 90.6, and 92.4 at 1, 3, 6, 9, 11, and 14 months, respectively, postoperatively. TKA was performed 8 months after THA. The Knee Society Score was 36 before TKA and 74, 82, and 90 at 1, 3, and 6 months, respectively, after TKA. The FJS of the knee was 36.6, 63.9, and 84.5 at 1, 3, and 6 months, respectively, after TKA. The patient's knee range of motion returned to normal, with significant reduction in pain and improved satisfaction levels after TKA. THA and TKA can achieve good clinical outcomes in patients with ochronosis accompanied by severe joint pain.

19.
Mech Ageing Dev ; 216: 111880, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37839614

ABSTRACT

Osteoarthritis (OA) is a prevalent disease among elderly people and is often characterized by chronic joint pain and dysfunction. Recently, growing evidence of chondrocyte senescence in the pathogenesis of OA has been found, and targeting senescence has started to be recognized as a therapeutic approach for OA. Piezo1, a mechanosensitive Ca2+ channel, has been reported to be harmful in sensing abnormal mechanical overloading and leading to chondrocyte apoptosis. However, whether Piezo1 can transform mechanical signals into senescence signals has rarely been reported. In this study, we found that severe OA cartilage expressed more Piezo1 and the senescence markers p16 and p21. 24 h of periodic mechanical stress induced chondrocyte senescence in vitro. In addition, we demonstrated the pivotal role of Piezo1 in OA chondrocyte senescence induced by mechanical stress. Piezo1 sensed mechanical stress and promoted chondrocyte senescence via its Ca2+ channel ability. Moreover, Piezo1 promoted SASP factors production under mechanical stress, particularly in IL-6 and IL-1ß. p38MAPK and NF-κB activation were two key pathways that responded to Piezo1 activation and promoted IL-6 and IL-1ß production, respectively. Collectively, our study revealed a connection between abnormal mechanical stress and chondrocyte senescence, which was mediated by Piezo1.


Subject(s)
Interleukin-6 , Osteoarthritis , Humans , Aged , Stress, Mechanical , Interleukin-6/metabolism , Osteoarthritis/metabolism , Signal Transduction , Gene Expression Regulation , Interleukin-1beta/metabolism , Chondrocytes/metabolism , Cellular Senescence/physiology
20.
Sci Data ; 10(1): 447, 2023 07 12.
Article in English | MEDLINE | ID: mdl-37438378

ABSTRACT

The past few decades have witnessed rapid progresses in the research and development of complex metallic alloys such as metallic glasses and multi-principal element alloys, which offer new solutions to tackle engineering problems of materials such as the strength-toughness conflict and deployment in harsh environments and/or for long-term service. A fatigue database (FatigueData-CMA2022) is compiled from the literature by the end of 2022. Data for both metallic glasses and multi-principal element alloys are included and analyzed for their statistics and patterns. Automatic extraction and manual examination are combined in the workflow to improve the efficiency of processing, the quality of published data, and the reusability. The database contains 272 fatigue datasets of S-N (the stress-life relation), ε-N (the strain-life relation), and da/dN-ΔK (the relation between the fatigue crack growth rate and the stress intensity factor range) data, together with the information of materials, processing and testing conditions, and mechanical properties. The database and scripts are released in open repositories, which are designed in formats that can be continuously expanded and updated.

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