Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

Complete telomere-to-telomere genomes uncover virulence evolution conferred by chromosome fusion in oomycete plant pathogens.

Variations in chromosome number are occasionally observed among oomycetes, a group that includes many plant pathogens, but the emergence of such variations and their effects on genome and virulence evolution remain ambiguous. We generated complete telomere-to-telomere genome assemblies for Phytophthora sojae, Globisporangium ultimum, Pythium oligandrum, and G. spinosum. Reconstructing the karyotype of the most recent common ancestor in Peronosporales revealed that frequent chromosome fusion and fission drove changes in chromosome number. Centromeres enriched with Copia-like transposons may contribute to chromosome fusion and fission events. Chromosome fusion facilitated the emergence of pathogenicity genes and their adaptive evolution. Effectors tended to duplicate in the sub-telomere regions of fused chromosomes, which exhibited evolutionary features distinct to the non-fused chromosomes. By integrating ancestral genomic dynamics and structural predictions, we have identified secreted Ankyrin repeat-containing proteins (ANKs) as a novel class of effectors in P. sojae. Phylogenetic analysis and experiments further revealed that ANK is a specifically expanded effector family in oomycetes. These results revealed chromosome dynamics in oomycete plant pathogens, and provided novel insights into karyotype and effector evolution.

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Sources apportionments of heavy metal(loid)s in the farmland soils close to industrial parks: Integrated application of positive matrix factorization (PMF) and cadmium isotopic fractionation.

Understanding the source identification and distribution of heavy metal(loid)s in soil is essential for risk management. The sources of heavy metal(loid)s in farmland soil, especially in areas with rapid economic development, were complicated and need to be explored urgently. This study combined geographic information system (GIS) mapping, positive matrix factorization (PMF) model and cadmium (Cd) isotope fingerprinting methods to identify heavy metal(loid) sources in a typical town in the economically developed Yangtze River Delta region of China. Cd, As, Cu, Zn, Pb, Ni and Co in different samples were detected. The results showed that Cd was the most severely contaminated element, with an exceedance rate of 78.0 %. GIS mapping results indicated that the hotspot area was located in the northeastern area with prolonged operational histories of electroplating and non-ferrous metal smelting industries. The PMF model analysis also identified emissions from smelting and electroplating enterprises as the main sources of Cd in the soil, counted for 49.28 %, followed by traffic (25.66 %) and agricultural (25.06 %) sources. Through further isotopic analysis, it was found that in soil samples near the industrial park, the contribution of electroplating and non-ferrous metal smelting enterprises to cadmium pollution was significantly higher than other regions. The integrated use of various methodologies allows for precise analysis of sources and input pathways, offering valuable insights for future pollution control and soil remediation endeavors.

Six-Part Classification of Femoral Intertrochanteric Fractures: A Classification Method to Improve the Diagnosis Rate of Unstable Fractures.

OBJECTIVE: Three-dimensional (3D)-CT data is currently insufficient for classifying femoral trochanter fractures. Fracture classification based on fracture stability analysis is helpful to evaluate the prognosis of patients after internal fixation. Currently, there is a lack of fracture classification methods based on 3D-CT images and fracture stability analysis. The aim of this study was to propose a new six-part classification method for intertrochanteric fractures of femur based on 3D-CT images and fracture stability analysis to improve the diagnosis rate of unstable fractures. METHOD: From January 2009 to December 2019, 320 patients receiving intramedullary nail surgery for femoral intertrochanteric fractures at Chengdu University's Affiliated Hospital were studied retrospectively. AO and six-part classifications were undertaken according to the 3D-CT image data of the patients, and the stability rates of two classifications were compared. According to the six-part classification stability criteria, the patients were divided into a stable and an unstable fracture group. The perioperative and follow-up indicators of the two groups were statistically analyzed, and the six-part classification's inter-observer and internal reliability was examined. RESULTS: There were 107 men and 213 females women the 320 patients, with an average age of 79.32 ± 11.26 years and an osteoporosis rate of 55.63% (178/320). The fracture stability rate of 39.69% (127/320) was studied using a six-part classification method. The AO classification fracture stability rate was 42.50% (136/320), with no significant difference (χ2 = 0.523, p = 0.470 > 0.05). There is no statistically significant difference between the two classification techniques in the examination of fracture stability (McNemer difference test p = 0.306 > 0.05; Kappa consistency test p < 0.001). According to the six-part classification, fracture stability and instability group were divided into two groups. The following indicators were compared between the two groups: The surgery time (p = 0.280), fracture reduction quality (p = 0.062); function independent measurement (p = 0.075); timed up and go test (TUG) (p = 0.191), and Parker-Palmer score (p = 0.146). Were as compared according to the six-part classification of stable and unstable fracture groups. Perioperative blood loss (p < 0.001), the Harris score excellent and good rate (p = 0.043), fracture healing time (p < 0.001), and the entire weight-bearing duration (p = 0.002) were statistically significant. The difference in femoral head height (FHH) (p = 0.046), the change in femoral neck shaft angle (p = 0.003), the change in medial cephalic nail length (p = 0.033), and the change in tip-apex distance (TAD) (p = 0.002) were statistically significant compared to the relevant markers of imaging stability. Fracture stability had a substantial influence on Harris ratings at 3, 6, and 12 months following surgery, according to repeated measures analysis of variance (F(1,126) = 32.604, p < 0.001). The effect of time on the Harris score was similarly significant (F(1.893,238.508) = 202.771, p < 0.001). The observer intra-observer inter-group correlation coefficient (ICC) value was 0.941 > 0.75, the inter-observer ICC value was 0.921 > 0.75, and the intra-observer and inter-observer reliability were both good. CONCLUSION: The six-part classification of femoral intertrochanteric fractures based on 3D-CT images has broader guiding relevance for femoral intertrochanteric fracture stability analysis. Clinicians will find this classification simpler and more consistent than the AO classification.

Epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China: a hospital-based retrospective study.

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Cyclical endometrial repair and regeneration: Molecular mechanisms, diseases, and therapeutic interventions.

The endometrium is a unique human tissue with an extraordinary ability to undergo a hormone-regulated cycle encompassing shedding, bleeding, scarless repair, and regeneration throughout the female reproductive cycle. The cyclical repair and regeneration of the endometrium manifest as changes in endometrial epithelialization, glandular regeneration, and vascularization. The mechanisms encompass inflammation, coagulation, and fibrinolytic system balance. However, specific conditions such as endometriosis or TCRA treatment can disrupt the process of cyclical endometrial repair and regeneration. There is uncertainty about traditional clinical treatments' efficacy and side effects, and finding new therapeutic interventions is essential. Researchers have made substantial progress in the perspective of regenerative medicine toward maintaining cyclical endometrial repair and regeneration in recent years. Such progress encompasses the integration of biomaterials, tissue-engineered scaffolds, stem cell therapies, and 3D printing. This review analyzes the mechanisms, diseases, and interventions associated with cyclical endometrial repair and regeneration. The review discusses the advantages and disadvantages of the regenerative interventions currently employed in clinical practice. Additionally, it highlights the significant advantages of regenerative medicine in this domain. Finally, we review stem cells and biologics among the available interventions in regenerative medicine, providing insights into future therapeutic strategies.

Progress in the application of 3D-printed sodium alginate-based hydrogel scaffolds in bone tissue repair.

In recent years, hydrogels have been widely used in the biomedical field as materials with excellent bionic structures and biological properties. Among them, the excellent comprehensive properties of natural polymer hydrogels represented by sodium alginate have attracted the great attention of researchers. At the same time, by physically blending sodium alginate with other materials, the problems of poor cell adhesion and mechanical properties of sodium alginate hydrogels were directly improved without chemical modification of sodium alginate. The composite blending of multiple materials can also improve the functionality of sodium alginate hydrogels, and the prepared composite hydrogel also has a larger application field. In addition, based on the adjustable viscosity of sodium alginate-based hydrogels, sodium alginate-based hydrogels can be loaded with cells to prepare biological ink, and the scaffold can be printed out by 3D printing technology for the repair of bone defects. This paper first summarizes the improvement of the properties of sodium alginate and other materials after physical blending. Then, it summarizes the application progress of sodium alginate-based hydrogel scaffolds for bone tissue repair based on 3D printing technology in recent years. Moreover, we provide relevant opinions and comments to provide a theoretical basis for follow-up research.

Microplastic formation and simultaneous release of phthalic acid esters from residual mulch film in soil through mechanical abrasion.

The application of plastic mulch film could effectively enhance the productivity of facility agriculture. However, releasing microplastic and phthalate from mulch films in soil has attracted increasing concerns, and releasing characters of microplastic and phthalate from mulch films during their mechanical abrasion remains unclear. This study elucidated the dynamics and impact factors of microplastic generation, including the thickness, polymer types and ageing of mulch film during mechanical abrasion. Releasing characters of the di(2-Ethylhexyl) phthalate (DEHP), a common type of phthalate in soil, from mulch film during mechanical abrasion were also explored. Results showed that 2 pieces of mulch film debris increased to 1291 pieces of microplastic after five days of mechanical abrasion, with exponential growth in the microplastic generation. After mechanical abrasion, the thinnest (0.008 mm) mulch film completely transformed into microplastics. However, the thicker mulch (>0.01 mm) suffered slight disintegration, making it feasible to be recycled. The biodegradable mulch film discharged the most microplastics (906 pieces) compared with the HDPE (359 pieces) and LDPE (703 pieces) mulch film after three days of mechanical abrasion. In addition, the mild thermal and oxidative ageing could result in 3047 and 4532 pieces of microplastic emissions from mulch film after three days of mechanical abrasion, which were ten times more than the original mulch film (359 pieces). Furthermore, negligible DEHP was released from mulch film without mechanical abrasion, while the released DEHP significantly correlated with generated microplastics during mechanical abrasion. These results demonstrated the crucial role of mulch film disintegration in phthalate emissions.

Bioinformatics evaluation of a novel angiogenesis related genes-based signature for predicting prognosis and therapeutic efficacy in patients with gastric cancer.

OBJECTIVE: Tumor angiogenesis plays a pivotal role in the development and metastasis of tumors. This study aimed to elucidate the association between angiogenesis-related genes (ARGs) and the prognosis of patients with gastric cancer (GC). METHODS: Transcriptomics and clinical data of GC samples were obtained from The Cancer Genome Atlas (TCGA) as the training group and those from Gene Expression Omnibus (GEO, including GSE26253, GSE26091 and GSE66229) as the validation groups. Single-sample gene set enrichment analysis (ssGSEA) was performed for gene set enrichment analysis on the gene set of angiogenesis and divided patients into high- or low-ARG group. Subsequently, to improve the availability of the ARG signature, a ARGs subtype predictor was then constructed by integrating of four machine learning methods, including support vector machine (SVM), least absolute shrinkage and selection operator (LASSO) regression, Random Forest and Boruta (RFB) and extreme gradient boosting (XGBoost). Kaplan-Meier and receiver operating characteristic curves were used to evaluate the performance of prognosis prediction. The EPIC and xCELL method were used to calculate the profile of tumor-infiltrated immune cells. RESULTS: The expression levels of a total of 36 ARGs that correlated with the survival of patients with GC were identified and utilized to establish an ARG-related prognosis signature. The area under the curve for predicting overall survival (OS) in the training group at the 1-, 3- and 5-year was 0.61, 0.64 and 0.76, respectively, and this was further validated using three independent GEO datasets. Moreover, the ARG signatures were significantly correlated with cancer-associated fibroblasts (CAFs), and GC patients that exhibited both high ARG expression level and matrix CAFs level had the most inferior outcomes. The multiple machine learning algorithms were applied to establish a 10-gene ARG subtype predictor, and notably, a high ARG-subtype predictor score was associated with reduced efficacy of immunotherapy, and potential anti-HER2 or FGFR4 therapy, but an increased sensitivity to anti-angiogenesis-related therapy. CONCLUSION: The novel ARGs-based classification may act as a potential prognostic predictor for GC and be used as a guidance for clinicians in selecting potential responders for immunotherapy and targeted therapy.

3D printed PCLA scaffold with nano-hydroxyapatite coating doped green tea EGCG promotes bone growth and inhibits multidrug-resistant bacteria colonization.

OBJECTIVES: 3D-printing scaffold with specifically customized and biomimetic structures gained significant recent attention in tissue engineering for the regeneration of damaged bone tissues. However, constructed scaffolds that simultaneously promote bone regeneration and in situ inhibit bacterial proliferation remains a great challenge. This study aimed to design a bone repair scaffold with in situ antibacterial functions. MATERIALS AND METHODS: Herein, a general strategy is developed by using epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, firmly anchored in the nano-hydroxyapatite (HA) and coating the 3D printed polymerization of caprolactone and lactide (PCLA) scaffold. Then, we evaluated the stability, mechanical properties, water absorption, biocompatibility, and in vitro antibacterial and osteocyte inductive ability of the scaffolds. RESULTS: The coated scaffold exhibit excellent activity in simultaneously stimulating osteogenic differentiation and in situ resisting methicillin-resistant Staphylococcus aureus colonization in a bone repair environment without antibiotics. Meanwhile, the prepared 3D scaffold has certain mechanical properties (39.3 ± 3.2 MPa), and the applied coating provides the scaffold with remarkable cell adhesion and osteogenic conductivity. CONCLUSION: This study demonstrates that EGCG self-assembled HA coating on PCLA surface could effectively enhance the scaffold's water absorption, osteogenic induction, and antibacterial properties in situ. It provides a new strategy to construct superior performance 3D printed scaffold to promote bone tissue regeneration and combat postoperative infection in situ.

3D-Printed Poly (P-Dioxanone) Stent for Endovascular Application: In Vitro Evaluations.

Rapid formation of innovative, inexpensive, personalized, and quickly reproducible artery bioresorbable stents (BRSs) is significantly important for treating dangerous and sometimes deadly cerebrovascular disorders. It is greatly challenging to give BRSs excellent mechanical properties, biocompatibility, and bioabsorbability. The current BRSs, which are mostly fabricated from poly-l-lactide (PLLA), are usually applied to coronary revascularization but may not be suitable for cerebrovascular revascularization. Here, novel 3D-printed BRSs for cerebrovascular disease enabling anti-stenosis and gradually disappearing after vessel endothelialization are designed and fabricated by combining biocompatible poly (p-dioxanone) (PPDO) and 3D printing technology for the first time. We can control the strut thickness and vessel coverage of BRSs by adjusting the printing parameters to make the size of BRSs suitable for small-diameter vascular use. We added bis-(2,6-diisopropylphenyl) carbodiimide (commercial name: stabaxol®-1) to PPDO to improve its hydrolytic stability without affecting its mechanical properties and biocompatibility. In vitro cell experiments confirmed that endothelial cells can be conveniently seeded and attached to the BRSs and subsequently demonstrated good proliferation ability. Owing to the excellent mechanical properties of the monofilaments fabricated by the PPDO, the 3D-printed BRSs with PPDO monofilaments support desirable flexibility, therefore offering a novel BRS application in the vascular disorders field.

Diaporthe Diversity and Pathogenicity Revealed from a Broad Survey of Soybean Stem Blight in China.

Many species in the fungal Diaporthe (anamorph Phomopsis) genus have become a group of the most important pathogens that cause seed decay, stem and pot blight, and stem canker in soybean production worldwide, resulting in significant yield loss. Due to increased disease prevalence but a lack of research, we performed an extensive field survey to isolate and identify the Diaporthe species associated with soybean stem blight in six provinces of China between 2019 and 2020. A total of 92 Diaporthe isolates were identified based on morphological and multilocus phylogenetic analysis and classified into six species: D. longicolla, D. unshiuensis, D. sojae, D. caulivora, D. tectonigena, and an unknown Diaporthe sp. The most frequently identified species was D. longicolla with 57 isolates. High genetic diversity was observed for the D. longicolla isolates, and haplotype network analysis revealed a mixed structure among the population in the six provinces. In comparative pathogenicity assays, different virulence levels were observed among the 92 Diaporthe isolates. The results of this study provide new insights into the Diaporthe spp. associated with soybean stem blight in China and can help in the development of effective management strategies.

Three-dimensional graphene encapsulated hollow CoSe2-SnSe2nanoboxes for high performance asymmetric supercapacitors.

Construction of metal selenides with a large specific surface area and a hollow structure is one of the effective methods to improve the electrochemical performance of supercapacitors. However, the nano-material easily agglomerates due to the lack of support, resulting in the loss of electrochemical performance. Herein, we successfully design a three-dimensional graphene (3DG) encapsulation-protected hollow nanoboxes (CoSe2-SnSe2) composite aerogel (3DG/CoSe2-SnSe2) via a co-precipitation method coupled with self-assembly route, followed by a high temperature selenidation strategy. The obtained aerogel possesses porous 3DG conductive network, large specific surface area and plenty of reactive active sites. It could be used as a flexible and binder-free electrode after a facile mechanical compression process, which provided a high specific capacitance of 460 F g-1at 0.5 A g-1, good rate capability of 212.7 F g-1at 10 A g-1The capacitance retention rate is 80% at 2 A g-1after 5000 cycles due to the fast electron/ion transfer and electrolyte diffusion. With the as-prepared 3DG/CoSe2-SnSe2as positive electrodes and the AC (activated carbon) as negative electrodes, an asymmetric supercapacitor (3DG/CoSe2-SnSe2//AC) was fabricated, which delivered a high specific capacity of 38 F g-1at 1 A g-1and an energy density of 11.89 Wh kg-1at 749.9 W kg-1, as well as excellent cycle stability. This work provides a new method for preparing electrode material.

Improved Whole-Genome Sequence of Fusarium meridionale, the Fungal Pathogen Causing Fusarium Head Blight in Rice.

Members of the Fusarium graminearum species complex (FGSC) cause extensive yield losses in cereal production worldwide, and food safety concerns due to the accumulation of Fusarium toxins in infected grains. Among these pathogens, F. meridionale is responsible for Fusarium head blight of wheat and rice, ear and stalk rot of maize, and pod blight of soybean. Here, we present an improved genome assembly of F. meridionale strain SR5 isolated from rice in China based on PacBio long-read sequencing and Illumina short-read sequencing technology. The assembled genome of SR5 has a total size of 36.82 Mb, an N50 scaffold length of 7.82 Mb, nine scaffolds, and encodes 12,409 predicted genes. These high-quality data expand FGSC genomic resources and provide a valuable resource for better understanding their genetic diversity and the molecular basis of pathogenesis, which will facilitate the development of an effective control strategy.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The effectiveness and safety of prophylactic central neck dissection in clinically node-negative papillary thyroid carcinoma patients: A meta-analysis.

Objective: This meta-analysis was performed to evaluate the effectiveness and safety of prophylactic central neck dissection (PCND) in patients with clinically node-negative (cN0) papillary thyroid carcinoma. Materials and methods: A meta-analysis of the literature was performed using the key words "papillary thyroid carcinomas" and "lymph node ecisions" for searches of electronic databases. Complications such as transient hypocalcemia, permanent hypocalcemia, transient and permanent hypoparathyroidism, transient and permanent vocal cord paralysis, transient recurrent and permanent recurrent laryngeal nerve injury, and local recurrence were pooled by meta-analysis. Stata17.0 was used to carry out the meta-analysis. Results: Data were extracted from 15 studies. In the present review, the group of patients who had total thyroidectomy (TT) with PCND had a lower local recurrence than the group with TT alone (OR 0.22, 95% CI 0.10-0.45, P = 0.000), whereas the incidence of permanent hypocalcemia (OR 4.24, 95% CI 1.05-17.22, P = 0.043) and transient hypoparathyroidism (OR 2.14, 95% CI 1.34-3.42, P =0.001) were higher. No significant differences were recorded in the incidence of other complications: transient hypocalcemia (OR 2.24, 95% CI 0.77-6.51, P = 0.138), permanent hypoparathyroidism (OR 1.70, 95% CI 0.89-3.27, P = 0.111), transient vocal cord paralysis (OR 1.48, 95% CI 0.78-2.83, P = 0.231), permanent vocal cord paralysis (OR 1.44, 95% CI 0.53-3.94, P = 0.477), transient recurrent laryngeal nerve injury (OR 1.47, 95% CI 0.93-2.32, P = 0.102) and permanent recurrent laryngeal nerve injury (OR 1.24, 95% CI 0.56-2.74, P = 0.587) between the two groups. Conclusion: Compared with TT alone, TT with PCND was more effective in reducing local recurrence without increasing the risk of recurrent laryngeal nerve, thyroid and vocal cord, except for hypocalcemia and transient hypoparathyroidism. Therefore, we believe that TT with PCND should be recommended for patients with cN0 PTC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD4202 2355078.

Genomic alterations in tumor tissue and ctDNA from Chinese pancreatic cancer patients.

Though the genomic feature of pancreatic cancer has been comprehensively studied in western patients, the genetic feature of Chinese patients is poorly clarified. In this study, a total of 225 pancreatic cancer patients were enrolled, mainly pancreatic ductal adenocarcinoma (PDAC, 97.33%). 140 patients (62.22%) provided sufficient tumor tissues for genomic analysis, and the rest (37.78%) were provided serum instead. Utilizing target next-generation sequencing (NGS), we analyzed genomic alterations of 618 selected genes. Corresponding data in the TCGA database were also analyzed here. In total, 26 (11.61%) patients had pathogenic or likely pathogenic germline variants, mainly (84.62%) involved genes in the DNA damage repair (DDR) pathway. The mean and median counts of somatic alterations per sample were 6.28 and 5, respectively. The most frequently mutated genes in our cohort were KRAS, TP53, CDKN2A, SMAD4, FBXW7 and ARID1A, revealing a significantly different prevalence of genes including KRAS, CDKN2A, ARID1A, NOTCH1, ARID1B than the corresponding data in the TCGA database. 39.11% of patients were identified with actionable alteration and the ratio was not significantly different between tissue and serum samples. 22.67% of patients harbored DDR gene alterations, which were associated with a higher tumor mutation burden. We also found that all the DDR alterations were not correlated with the overall survival and immune and stroma score, but the changes in NK cells and follicular T cells were identified in samples with DDR changes according to TCGA database. In summary, we identified a distinct genomic feature of Chinese pancreatic cancer patients by comparing with the data in TCGA database, and suggested the role for genetic testing using tissue or ctDNA samples in decision-making process. DDR alterations were associated with a higher tumor mutation burden and the significantly higher counts of NK cells in DDR altered samples may raise the attention in future related drugs development.

The risk assessment model of fracture nonunion after intramedullary nailing for subtrochanteric femur fracture.

ABSTRACT: To investigate the influencing factors of fracture nonunion after intramedullary nailing for subtrochanteric fractures and to construct a risk assessment model.Based on the multicenter retrospective analysis of 251 patients, all patients were divided into modeling group and verification group. In the modeling group, postoperative fracture nonunion rate, general data, fracture-related factors, surgical reduction-related factors, mechanical and biological factors were calculated, and the influencing factors of fracture nonunion were screened by univariate analysis. Logistic regression model was used for multifactor analysis to construct the risk assessment model. Based on the logistic regression model, the risk prediction model was constructed by drawing the Nomogram diagram. Through the verification group, the influencing factors were evaluated again, and the differentiation and calibration of the model were evaluated. The calibration degree was evaluated by Hosmer-Lemeshow test, goodness of fit test, and calibration curve. The discriminant degree was evaluated by the receiver operating characteristic curve.Fracture nonunion occurred in 34 of 149 patients in the modeling group. Among the 14 potential influencing factors, univariate analysis and logistic regression analysis showed that postoperative hip varus, intramedullary nail fixation failure, and reduction of fracture with large incision were the risk factors of fracture nonunion. The medial cortex fracture was seen reduced on X-Ray was a protective factor for fracture nonunion, and a regression equation was established. Based on the logistic regression model, the Nomogram diagram is drawn. Twenty-four cases of fracture nonunion occurred in the verification group. The area under the receiver operating characteristic curve was area under curve =0.883 > 0.7, indicating that there was a moderate differentiation to evaluate the occurrence of fracture nonunion after operation. The goodness of fit test: the Hosmers-Lemeshow test (X2 = 2.921, P = .712 > .05) showed that the model had a good calibration.After intramedullary nailing of subtrochanteric fracture, hip varus, failure of intramedullary nail fixation and wide surgical dissection are the risk factors of fracture nonunion, and the postoperative reduction of medial cortex fracture is protective factor.National key research and development projects: 2016YFC0105806.

Potassium voltage-gated channel subfamily D member 2 induces an aggressive phenotype in lung adenocarcinoma.

The study aimed to investigate the roles of potassium voltage-gated channel subfamily D member 2 (KCND2) in lung adenocarcinoma (AD). RNA sequencing data from The Cancer Genome Atlas (TCGA) database showed that the expression of KCND2 was elevated in lung AD samples compared to the normal samples, and its upregulation was significantly associated with the unfavorable clinic outcome of lung AD patients. Cell proliferation and transwell assays revealed that the growth, migration, and invasion of lung AD cells, which was crucial to cancer aggressiveness, were markedly inhibited after the depletion of KCND2. Importantly, we demonstrated that the depletion of KCND2 suppressed the biological behaviors of lung AD cells via restraining the expression of four tumor-related genes including PCNA, CDH2, SNAI1, and MMP2. Overall, KCND2 promotes the aggressiveness of lung AD and can be considered as a potential predictor of the prognosis of lung AD patients. Downregulation of KCND2 may contribute to the therapy of lung AD.

Evaluation of the reliability and validity of Functional Assessment Of Chronic Illness Therapy-Spiritual Well-Being-Expanded in elderly patients with chronic orthopaedic diseases.

BACKGROUND: The Functional Assessment Of Chronic Illness Therapy-Spiritual Well-Being-Expanded (FACIT-Sp-Ex) scale can simultaneously evaluate the quality of life and spiritual health level of patients with chronic orthopaedic diseases. We performed the FACIT-Sp-Ex scale in Chinese, and tested its reliability and validity in patients with chronic orthopaedic diseases. METHODS: There were 249 patients with chronic orthopaedic diseases who were selected for the questionnaire survey. AMOS 23.0 and SPSS 25.0 were used for statistical analysis to calculate the reliability and validity of the Chinese version of the scale. RESULTS: The Chinese version of FACIT-Sp-Ex scale showed that root mean square error of approximation (RMSEA) was 0.06. Cronbach's alpha coefficient was 0.83, the subscale was 0.72 ~ 0.82. The meaning, peace, relational subscales and total scale of the FACIT-Sp-Ex were negatively correlated with hospital anxiety and depression scale (HADS) and positively correlated with health-related quality of life (HRQOL). All four subdomains were inversely associated with HADS anxiety symptoms, the peace and relational subscales were inversely associated with HADS depressive symptoms. Elderly female patients score higher than male patients in faith subscale. The highest-scoring disease in FACIT-Sp-Ex faith scale was osteoarthritis, which in FACIT-Sp-Ex total scale are piriformis syndrome and osteoarthritis. CONCLUSION: The Chinese version of FACIT-Sp-Ex scale has good reliability and validity, which can be used as an evaluation tool for the spiritual status and quality of life of Chinese elderly chronic orthopaedic patients.