Intracellular Staphylococcus aureus infection in human osteoblasts: circRNA expression analysis.

Staphylococcus aureus (S. aureus) has the ability to invade human cortical bones and cause intracellular infections in osteoblasts, which may lead to a long-term infection that is difficult to eliminate. It is critical to identify the underlying mechanisms of the osteoblast response to the intracellular S. aureus. More recently, multiple circular RNA (circRNA) functions have been identified, including serving as protein scaffolds or miRNA sponges and being translated into polypeptides. The role that circRNAs play in intracellular S. aureus infection of osteoblasts has not, to our knowledge, been investigated. Here, we established an intracellular infection model of S. aureus in osteoblasts and compared the circRNA expression of osteoblasts between the infected and control groups using RNA sequencing technology, by which a significant difference was found. In total, 117 upregulated and 125 down-regulated differentially expressed circRNAs (DEcircRNAs) were identified, and reverse transcription-quantitative PCR was employed to validate the results of RNA sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that DEcircRNAs were enriched in processes associated with macromolecule modification, cellular component organization or biogenesis, and intracellular non-membrane-bound organelles. Finally, a potentially important network of circRNA-miRNA-mRNA based on the DEcircRNAs was constructed. Overall, this study revealed the circRNA expression profile of human osteoblasts infected by intracellular S. aureus for the first time, and identified the circRNAs that may contribute to the pathogenesis of infectious diseases caused by intracellular S. aureus infection in human osteoblasts.

Gender differences in the impact of anatomical factors on non-contact anterior cruciate ligament injuries: a magnetic resonance study.

PURPOSE: To identify MRI-detected anatomical risk factors for non-contact anterior cruciate ligament (ACL) injuries across genders. METHODS: A retrospective analysis was performed on 141 ACL-reconstructed patients (35 females, 106 males) and 142 controls (37 females, 105 males) from January 2020 to April 2022. Inclusion criteria were primary non-contact ACL injuries. The tibial plateau slope, lateral femoral condyle index, Insall-Salvati index, and patellar tendon angle were measured, using binary logistic regression for gender-specific risk evaluation. RESULTS: Increased lateral tibial plateau slope, reduced intercondylar notch width index, lateral femoral condyle index, and patellar tendon angle correlated with ACL injuries in both genders. The Insall-Salvati index was a significant risk factor in females but not in males. CONCLUSION: This study identifies the lateral tibial plateau slope, notch width index, lateral femoral condyle index, and patellar tendon angle at near-extension as risk factors for ACL injuries in both genders, with the Insall-Salvati index also implicated in females.

Contributing Risk Factors to Self-Contamination During the Process of Donning and Doffing Personal Protective Equipment.

OBJECTIVE: The goal of this study is to explore the risk factors associated with self-contamination points during personal protective equipment (PPE) donning and doffing among health care workers (HCWs). METHODS: In total, 116 HCWs were randomly sampled and trained to don and doff the whole PPE set. We smeared the whole PPE set with the fluorescent powder. After each participant finished PPE doffing, the whole body was irradiated with ultraviolet light in order to detect contamination points and record the position and quantity. Sociodemographic characteristics and previous infection prevention control (IPC) training experience, among others, were collected by using electronic questionnaires. Poisson regression was used in identifying risk factors that are associated with the number of contamination points, and the relative risk (RR) and its 95% confidence interval (CI) were calculated. RESULTS: About 78.5% of participants were contaminated. Ever training experience (RR = 0.37; 0.26, 0.52), clinical departments (RR = 0.67; 0.49, 0.93), body mass index (BMI) (RR = 1.09; 1.01, 1.18), and shoulder width (RR = 1.07; 1.01, 1.13) were associated with the number of contamination points. CONCLUSIONS: Previous IPC training experience, department types, BMI, and shoulder width were associated with self-contamination points after the PPE was removed.

GLIM criteria represent a more suitable tool to evaluate the nutritional status and predict postoperative motor functional recovery of older patients with hip fracture: A retrospective study.

Early recognition of malnutrition is essential to improve the prognosis of older patients with hip fracture. The Nutritional Risk Screening 2002 (NRS-2002), the Short-Form Mini Nutritional Assessment (MNA-SF) and the Global Leadership Initiative on Malnutrition (GLIM) are widely used in malnutrition diagnosis. However, criteria for predicting postoperative hip joint motor function in older patients with hip fractures are still necessary. The objective of this study was to select the most appropriate criteria from the NRS-2002, the MNA-SF and the GLIM in predicting the postoperative hip joint motor function recovery 1 year after surgery. This retrospective observational study included 161 patients aged ≥ 65 years with hip fractures. The nutritional status of patients was determined by the NRS-2002, MNA-SF and GLIM. The Harris hip joint score (HHS), the primary outcome of this study, was used to evaluate hip joint motor function. HHS was classified as excellent (HHS > 75) or non-excellent outcomes (HHS ≤ 75). Logistic regression models for hip joint motor function recovery were constructed. Both the receiver operating characteristic curve and the decision curve analysis were used to select the most predictive criteria. The overall mean age of the 161 patients was 77.90 ±â€…8.17. As a result, NRS-2002 (OR:0.06, 95%CI [0.01, 0.17]), MNA-SF (OR:0.05, 95%CI [0.00, 0.23]) and GLIM (OR of moderate: 0.03, 95%CI [0.01, 0.11]; OR of severe: 0.02 [0.00, 0.07]) were predictive for recovery of hip joint motor function. Additionally, both the area under curve of the receiver operating characteristic curve (NRS-2002: 81.2 [73.8, 88.6], MNA-SF: 76.3 [68.5, 84.2], GLIM: 86.2 [79.6,92.8]) and the decision curve analysis showed the GLIM was better than others. Compared with NRS-2002 and MNA-SF, GLIM was a more suitable nutritional assessment criteria to predict the postoperative recovery of hip joint motor function for older patients with hip fracture 1 year after surgery.

Biomechanics and finite element analysis comparing posterior T-plates with LCP for fixation of posterolateral tibial plate fractures.

Objective: The treatment for posterolateral tibial plateau fractures (PTPF) have been subjects of controversy. We conducted a study to improve the fixation of PTPF through a lateral approach. Methods: We utilized 40 synthetic tibias and categorized the fracture models into five groups based on the locking compression plate (LCP) and T-distal radius plate (TPP) via various forms of fixation with screws through the posterolateral (PL) fracture fragments. I: Two-screw fixation using two locking screws (LPTL). Ⅱ: Two-screw fixation with both variable angle locking screws (LPTV). Ⅲ: One-screw fixation with one locking screw (LPOL). Ⅳ: One-screw fixation with one locking screw and two anteroposterior lag screws (LPOLTL). Ⅴ: a distal radius plate with three locking screws (TPP). Biomechanical tests were conducted to observe the axial compression displacement of the PL fracture fragments at force levels of 250 N, 500 N, and 750 N, as well as to determine the failure load and the axial stiffness for each respective group. Results: Under a 750 N load condition, the displacements within the five experimental groups exhibited the following trend: Ⅴ < Ⅱ < Ⅰ< Ⅳ < Ⅲ. However, there were no significant differences between Group V and Group II, Group I and Group IV (p > 0.05), and only Group Ⅲ demonstrated a displacement exceeding 3 mm. The failure load and the axial stiffness exhibited the same trend. Conversely, statistical significance was identified among the remaining group compared with Group Ⅲ (p < 0.05). Regarding the finite element analysis, the maximum displacements for the five models under the load of 750 N exhibited the following trend: Ⅴ < Ⅱ < Ⅰ< Ⅳ < Ⅲ. The following trends were observed in maximum von Mises stresses for these models under the load of 750 N: Ⅴ < Ⅱ < Ⅳ< Ⅰ < Ⅲ. Conclusion: It is crucial to address the inadequate mechanical strength associated with single screw fixation of LCP for fixing PL fractures in a clinical setting. The biomechanical strength of two-screw fixation surpasses that of single-screw fixation. Introducing variable-angle screws can further enhance the fixation range. Furthermore, the addition of two lag screws threaded from anterior to posterior can compensate the mechanical stability, when PL fracture is fixed with single screw in clinic.

Potential problem and solution of lateral plate postposition for the posterolateral tibial plateau fracture.

BACKGROUND: There has been controversial for the treatment of the posterolateral tibial plateau fractures (PTPF). This study aimed to evaluate clinic outcomes of the lateral locking compression plate (LCP) postposition, analyze the feasibility of LCP postposition through anatomical measurement, and address the potential problems of LCP postposition through the biomechanical assessment. METHODS: 39 patients with PTPF undergoing LCP fixation between June 2019 and June 2022 were retrospectively evaluated. All cases were divided into two group: Group A (15 cases) employed plate transverse arm postpositioning with posterolateral (PL) fracture fixation using two raft screws, while Group B (24 cases) utilized non-postpositioning with fixation by a single raft screw. Surgical duration, intraoperative blood loss, the change of lateral tibial plateau angle (LTPA), lateral tibial plateau posterior slope angle (LPSA) and fracture collapse between immediate postoperative and last follow up, range of motion (ROM), HSS knee score, and Lysholm knee score were recorded. CT measurements of the fibular head superior space and LCP transverse arm were taken in 50 healthy adult knees to assess postposition feasibility. Finally, three fracture models were established using finite element analysis: Model A with plate postposition and PL split fracture fixed by two raft screws of transverse arm, Model B with plate non-postposition and PL split fracture fixed by one raft screw, and Model C with plate non-postposition and PL split fracture fixed by one raft screw and anterior-posterior tension screws. Loadings of 250N, 500N, and 750N were applied for the analysis of the displacement degree, von Mises stress distribution. RESULTS: Results indicate comparable operative duration and intraoperative hemorrhage between groups. Complications were minimal in both groups. Group A demonstrated superior outcomes in terms of radiographic parameters, functional scores, and fracture collapse prevention. CT measurements revealed compatibility in 72% of healthy knees with the postpositioning technique. Finite element analysis indicated favorable biomechanical stability. CONCLUSION: Not all patients with PTPF were applicable to the management of the plate postposition and two raft screws fixation, even though this technique exerted good biomechanical stability and achieved satisfactory clinic outcomes. When the PL fracture was fixed by only raft screw through LCP owing to various reasons, two anterior-posterior tension screws might be necessitated to maintain the fracture stability.

Identification of mitochondria-related action targets of quercetin in melanoma cells.

Melanoma is a complex and genetically heterogeneous malignant tumor with high rates of mortality. Although current therapies provide a short-term clinical benefit, they are unable to cure the majority of patients with metastatic melanoma. Therefore, the investigation of pathological mechanisms and the development of new therapy strategies for melanoma are of great significance. Quercetin can effectively inhibit tumor growth in various tumors. However, the exact action mechanisms of quercetin against melanoma have not been comprehensively clarified, which limits its application. Accumulating evidence has suggested that the dysfunction of mitochondria is closely linked to carcinogenesis, and a better understanding of the regulation of mitochondria-related genes will shed light on providing new therapies for melanoma. In this study, we performed RNA-seq from melanoma B16-F1 cells treated with quercetin versus controls and screened for differentially expressed genes (DEGs). GO and KEGG enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Combining the results of RNA-seq, molecular docking, and bioinformatics analysis, we found six mitochondria-related genes, BTG2, CP, LRIG1, CYP1A1, GBP2, and MBNL1, which might be targets of quercetin in melanoma and provide an available targeting therapy strategy for melanoma.

The degree of fracture reduction does not compromise the clinical efficacy of arthroscopic reduction and fixation of tibial posterior cruciate ligament avulsion fractures: A retrospective study.

This study aimed to explore the postoperative outcomes of patients who underwent arthroscopic internal fixation with repositioning sutures for the treatment of posterior cruciate ligament (PCL) avulsion fractures with poorly reduced fracture fragments. It was hypothesized that improperly repositioned fracture fragments might not influence the postoperative clinical outcomes in patients with PCL avulsion fractures treated by arthroscopic sutures. From January 2020 to December 2021, patients admitted to our hospital with PCL avulsion fractures were evaluated. Our inclusion criteria were as follows: diagnosis of PCL avulsion fracture as Meyers & McKeever Type II or Type III; underwent arthroscopic double tunnel suture fixation; and age below 70. Of the patients meeting these criteria, data from 34 individuals were collected by a designated follow-up officer. Based on postoperative imaging, the patients were divided into 2 groups: well fracture reduction and poor fracture reduction groups. Prior to the surgery, the Lysholm score, knee mobility, and international knee documentation committee (IKDC score) were recorded for both groups. At the 3-month post-surgery mark, CT-3D reconstruction was performed. Statistical analysis was conducted on the collected data. For data that conformed to a normal distribution, the t test was applied. For data that didn't conform, we used a non-parametric test. Both groups achieved successful wound healing without encountering any adverse events, such as fracture nonunion infection. Fracture healing was observed in both groups at the 3-month postoperative mark. The average follow-up duration was 13.24 ± 6.18 months. There were no significant differences in Lysholm score, IKDC score, or knee mobility between the well- and poorly-reduced groups at the final follow-up (P > .05). Postoperatively, both groups demonstrated significant improvements in knee function compared to the preoperative scores, with statistically significant differences observed in Lysholm score, IKDC score, and knee mobility (P < .05). Arthroscopic fixation with double-tunnel sutures proved to be a highly effective treatment approach for PCL avulsion fractures, even in cases where the fractures were poorly reduced. Remarkably, there were no significant differences observed in postoperative knee function between the well- and poorly-reduced groups, indicating that both groups achieved favorable outcomes.

Identification of Anti-SNRPA as a Novel Serological Biomarker for Systemic Sclerosis Diagnosis.

Systemic sclerosis (SSc) is a systemic autoimmune disorder that leads to vasculopathy and tissue fibrosis. A lack of reliable biomarkers has been a challenge for clinical diagnosis of the disease. We employed a protein array-based approach to identify and validate SSc-specific autoantibodies. Phase I involved profiled autoimmunity using human proteome microarray (HuProt arrays) with 90 serum samples: 40 patients with SSc, 30 patients diagnosed with autoimmune diseases, and 20 healthy subjects. In Phase II, we constructed a focused array with candidates identified antigens and used this to profile a much larger cohort comprised of serum samples. Finally, we used a western blot analysis to validate the serum of validated proteins with high signal values. Bioinformatics analysis allowed us to identify 113 candidate autoantigens that were significantly associated with SSc. This two-phase strategy allowed us to identify and validate anti-small nuclear ribonucleoprotein polypeptide A (SNRPA) as a novel SSc-specific serological biomarker. The observed positive rate of anti-SNRPA antibody in patients with SSc was 11.25%, which was significantly higher than that of any disease control group (3.33%) or healthy controls (1%). In conclusion, anti-SNRPA autoantibody serves as a novel biomarker for SSc diagnosis and may be promising for clinical applications.

Multidrug-Resistant Organism Infections of Inpatients in a Hospital in Eastern China from 2015 to 2021.

Background: The prevalence of multidrug-resistant organisms (MDRO) is gradually increasing in the global scope, causing serious burden to patients and society, which is an important public health problem. Objective: To analyze the distribution and trend of MDROs and provide a reference for hospital infection control. Methods: Collected data on MDROs infections among inpatients in a Grade III Level A hospital in Suzhou from 2015 to 2021, including drug-resistant bacteria strains and specimen sources, etc. Mantel-Haenszel χ2 test was used to evaluate the trend of infection rates over the years and SPSS version 26.0 was used for statistics analysis. Results: The hospital infection rate showed an overall downward trend across the seven-year period, ranging from 1.53% to 2.10%. According to the analysis of change of drug-resistant bacteria strains, the highest infection rate was carbapenem-resistant Acinetobacter baumannii (CRABA) (63.74%), followed by methicillin-resistant Staphylococcus aureus (MRSA) (46.37%), carbapenem-resistant Pseudomonas aeruginosa (CRPAE) (24.87%), carbapenem-resistant Enterobacteriaceae (CRE) (13.14%) and vancomycin-resistant Enterococcus (VRE) (0.42%). The results of Mantel-Haenszel χ2 test showed that there was a linear relationship between the detection rate of CRE and CRPAE and the time (P<0.001), but the correlation was not strong (R = 0.136; R = 0.139). The overall detection rate of the five pathogens also increased (P<0.001). The majority of the specimens, mainly from sputum, airway secretions, and midstream urine, had a detection rate of over 70%. Conclusion: Our data showed that the detection rate of MDROs generally increased from 2015 to 2021, although the hospital infection rate displayed a declining trend. Among the detection rate MDROs, the highest was CRABA, and the lowest was VRE. It is necessary to enhance the prevention, control, and management of MDROs infections in the clinical practice.

Elevated serum levels of human epididymis protein 4 in adult patients with proliferative lupus nephritis.

Background: This study aimed to access whether serum human epididymis protein 4 (HE4) level could identify lupus nephritis (LN) pathological classes in adults and children. Methods: The serum HE4 levels of 190 healthy subjects and 182 patients with systemic lupus erythematosus (SLE) (61 adult-onset LN [aLN], 39 childhood-onset LN [cLN], and 82 SLE without LN) were determined using Architect HE4 kits and an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Results: Serum HE4 level was significantly higher in the aLN patients (median, 85.5 pmol/L) than in the patients with cLN (44 pmol/L, P < 0.001) or SLE without LN (37 pmol/L, P < 0.001), or the healthy controls (30 pmol/L, P < 0.001). Multivariate analysis showed that serum HE4 level was independently associated with aLN. Stratified by LN class, serum HE4 level was significantly higher in the patients with proliferative LN (PLN) than in those with non-PLN, and this difference was found only in aLN (median, 98.3 versus 49.3 pmol/L, P = 0.021) but not in cLN. Stratified by activity (A) and chronicity (C) indices, the aLN patients with class IV (A/C) possessed significantly higher serum HE4 levels than those with class IV (A) (median, 195.5 versus 60.8 pmol/L, P = 0.006), and this difference was not seen in the class III aLN or cLN patients. Conclusion: Serum HE4 level is elevated in patients with class IV (A/C) aLN. The role of HE4 in the pathogenesis of chronic lesions of class IV aLN needs further investigation.

Chemotherapy-Sensitized In Situ Vaccination for Malignant Osteosarcoma Enabled by Bioinspired Calcium Phosphonate Nanoagents.

How to effectively treat malignant osteosarcoma remains clinically challenging. Programmed delivery of chemotherapeutic agents and immunostimulants may offer a universal strategy for killing osteosarcoma cells while simultaneously eliciting in situ antitumor immunity. However, targeted chemoimmunotherapy lacks a reliable delivery system. To address this issue, we herein developed a bioinspired calcium phosphonate nanoagent that was synthesized by chemical reactions between Ca2+ and phosphonate residue from zoledronic acid using bovine serum albumin as a scaffold. In addition, methotrexate combination with a phosphorothioate CpG immunomodulator was also loaded for pH-responsive delivery to enable synergistic chemoimmunotherapy of osteosarcoma. The calcium phosphonate nanoagents were found to effectively accumulate in osteosarcoma for nearly 1 week, which is favorable for exerting the vaccination effects in situ by maturing dendritic cells and priming CD8+ T cells to suppress the osteosarcoma progression and pulmonary metastasis through controlled release of the three loaded agents in the acidic tumor microenvironment. The current study may thus offer a reliable delivery platform for achieving targeted chemotherapy-induced in situ antitumor immunity.

Impacts of delta and omicron variants on inactivated SARS-CoV-2 vaccine-induced T cell responses in patients with autoimmune diseases and healthy controls.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), which is still devastating economies and communities globally. The increasing infections of variants of concern (VOCs) in vaccinated population have raised concerns about the effectiveness of current vaccines. Patients with autoimmune diseases (PAD) under immunosuppressant treatments are facing higher risk of infection and potentially lower immune responses to SARS-CoV-2 vaccination. METHODS: Blood samples were collected from PAD or healthy controls (HC) who finished two or three doses of inactivated vaccines. Spike peptides derived from wild-type strain, delta, omicron BA.1 were utilised to evaluate T cell responses and their cross-recognition of delta and omicron in HC and PAD by flow cytometry and ex vivo IFNγ-ELISpot. RESULTS: We found that inactivated vaccine-induced spike-specific memory T cells were long-lasting in both PAD and HC. These spike-specific T cells were highly conserved and cross-recognized delta and omicron. Moreover, a third inactivated vaccine expanded spike-specific T cells that responded to delta and omicron spike peptides substantially in both PAD and HC. Importantly, the polyfunctionality of spike-specific memory T cells was preserved in terms of cytokine and cytotoxic responses. Although the extent of T cell responses was lower in PAD after two-dose, T cell responses were boosted to a greater magnitude in PAD by the third dose, bringing comparable spike-specific T cell immunity after the third dose. CONCLUSION: Inactivated vaccine-induced spike-specific T cells remain largely intact against delta and omicron variants. This study expands our understanding of inactivated vaccine-induced T cell responses in PAD and HC, which could have important indications for vaccination strategy.

Several genetic variants associated with systemic sclerosis in a Chinese Han population.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease with ethnic differences. Single-nucleotide polymorphisms (SNPs) in the ARID3A, CXCR5, and TNFSF8 genes have been reported to be associated with various autoimmune diseases. The aim of this study was to investigate the association between these SNPs and susceptibility to SSc in a Chinese Han population. METHODS: A case-control study was conducted in 342 patients with SSc and 694 ethnically matched healthy controls. SNPs in ARID3A, CXCR5, and TNFSF8 were genotyped using a Sequenom MassArray iPLEX system, and allele association analyses were performed using the PLINK v1.90 software. RESULTS: Our study demonstrated that the ARID3A rs10415976 G and CXCR5 rs77871618 T alleles were suggestively associated with patients with SSc (P = 0.049 and P = 0.024, respectively) and TNFSF8 rs1555457 T allele was strongly associated with SSc (P = 0.003). Patients carrying the ARID3A rs350146 TT and TNFSF8 rs1555457 TT genotypes had a significant increased risk of SSc (P = 0.03 and P = 0.004, respectively). Moreover, rs10415976, rs77871618, and rs1555457 were associated with SSc in an additive genetic model (P < 0.05). rs62132345 and rs1555457 were associated with SSc in the dominant genetic model (P < 0.05). rs350146 was associated with SSc in the recessive genetic model (P = 0.029). CONCLUSIONS: ARID3A rs10415976, ARID3A rs350146, and CXCR5 rs77871618 were suggestively associated with SSc and TNFSF8 rs1555457 was strongly associated with SSc in the Chinese Han population in this study. Key Points • This case-control study determined that ARID3A rs10415976, ARID3A rs350146 and CXCR5 rs77871618 were suggestively associated with SSc and TNFSF8 rs1555457 was strongly associated with SSc in the Chinese Han population. • The differences in these results compared with previous studies may be a result of ethnic and racial differences.

Circulating VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis.

OBJECTIVES: The objective of the current study was to detect plasma profiles of inflammatory cytokines for determining potential biomarkers indicating cancer presence among the anti-TIF1-γ antibody-positive dermatomyositis (DM) patients. METHODS: Twenty-seven cancer-associated anti-TIF1-γ antibody-positive DM (Cancer TIF1-γ-DM) patients were compared with 20 anti-TIF1-γ antibody-positive DM patients without cancer (Non-cancer TIF1-γ-DM) and 10 healthy controls (HC). The plasma levels of 17 cytokines were determined using the Luminex 200 system. The ability of plasma VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ levels to distinguish the presence of cancer was evaluated through the area under the curve (AUC) analysis. Potential protein interactions of TIF1-γ and the five cytokines were analyzed using the STRING database. RESULTS: VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ plasma levels were significantly higher in the Cancer TIF1-γ-DM group, especially those without any anticancer treatment, than those in the non-cancer TIF1-γ-DM and HC groups. Meanwhile, anti-TIF1-γ antibody and the five cytokines could distinguish cancer presence in anti-TIF1-γ antibody-positive DM patients. The STRING network indicated that TIF1-γ potentially interacted with the cytokines. Positive correlations of VEGF-A among CCL2, IL-6, and IFN-γ and between IFN-γ and IL-6 were observed in Cancer TIF1-γ-DM patients. VEGF-A, TNF-α, CCL2, and IL-6 were positively associated with muscle-associated enzymes among the Cancer TIF1-γ-DM patients. CONCLUSION: The present study identified VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as significant potential biomarkers indicating the presence of cancer and demonstrated a more detailed cytokine profile during diagnosis. These biomarkers could provide better screening strategies and insight into the Cancer TIF1-γ-DM pathogenesis. Key Points • VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ are potential biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis. Potential pathogenic molecular mechanism of the cancer-associated anti-TIF1-γ antibody-positive dermatomyositis.

Gadolinium-Bisphosphonate Nanoparticle-Based Low-Dose Radioimmunotherapy for Osteosarcoma.

Osteosarcoma is a malignant osteogenic tumor with a high metastatic rate commonly occurring in adolescents. Although radiotherapy is applied to treat unresectable osteosarcoma with radiation resistance, a high dose of radiotherapy is required, which may weaken the immune microenvironment. Therefore, there is an urgent need to develop novel agents to maximize the radiotherapeutic effects by eliciting immune activation effects. In this study, we synthesized therapeutic gadolinium-based metal-bisphosphonate nanoparticles (NPs) for osteosarcoma treatment that can be combined with radiotherapy. The gadolinium ion (Gd) was chelated with zoledronic acid (Zol), a commonly used drug to prevent/treat osteoporosis or bone metastases from advanced cancers, and stabilized by ovalbumin (OVA) to produce OVA-GdZol NPs. OVA-GdZol NPs were internalized into K7M2 osteosarcoma cells, showing a high sensitization effect under X-ray irradiation. Cell pretreatment of OVA-GdZol NPs significantly enhanced the radiation therapeutic effect in vitro by reducing the cell colonies and increased the signal of γH2AX-positive cells. More importantly, OVA-GdZol NPs promoted the maturation of bone marrow-derived dendritic cells (BMDCs) and M1 polarization of macrophages. The inhibitory effect on K7M2 osteosarcoma of OVA-GdZol NPs and X-ray radiation was evident, indicated by a significantly reduced tumor volume, high survival rate, and decreased lung metastasis. Meanwhile, both innate and adaptive immune systems were activated to exert a strong antitumor effect. The above results highly suggest that OVA-GdZol NPs serve as both radiosensitizers and immune adjuvants, suitable for the sequential combination of vaccination and radiotherapy.

Mid-term study on the effects of arthroscopic discoid lateral meniscus plasty on patellofemoral joint: An observational study.

In the present study, we aimed to investigate the clinical outcomes of arthroscopic discoid lateral meniscus (DLM) plasty and the adaptive changes in the patellofemoral joint after surgery. From September 2010 to March 2012, 25 patients with DLM injuries who underwent arthroscopic meniscus plasty were enrolled in the prospective study. All patients underwent clinical evaluation before the operation and at the last follow-up, and imaging evaluation was performed by upright magnetic resonance imaging before and 1 month after the operation as well as at the last follow-up. Clinical evaluation included Lysholm score, Kujala score, McMurray's sign, patellar mobility, patella grind test, and quadriceps atrophy. Imaging evaluation included bisect offset index, patella tilt angle (PTA), and cartilage damage. Lysholm score, Kujala score, McMurray's sign, and quadriceps atrophy at the last follow-up were significantly improved compared with the preoperative levels (P < .05). At the last follow-up, there were no statistical differences in patella mobility and patella grind test compared with the preoperative levels. In addition, bisect offset index and PTA showed a dynamic trend of rising and then falling over time (P < .05). At 1 month after the operation, bisect offset index and PTA were significantly increased compared with the preoperative levels or the values at the last follow-up (P < .05), while there were no differences between the preoperation and the last follow-up. Cartilage damage became worse with time (P < 0.05), and the 2 were positively correlated (Spearman = 0.368). At the last follow-up, the degree of cartilage damage was significantly increased compared with the preoperative level (P < .017), while there was no significant difference between the 1-month postoperative grade and the preoperational grade or the last follow-up grade. The effect of arthroscopic DLM plasty on the patellofemoral joint was dynamic, with the position of the patella deviating in the early stages and recovering in the mid-term, especially when the knee was in the biomechanical standing position. In addition, the patellofemoral joint cartilage might undergo accelerated degeneration after the operation, while the mid-term effect of the operation was positive, and the patellofemoral joint function was acceptable.

A fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain.

The effectiveness of a 3rd dose of SARS-CoV-2 vaccines waned quickly in the Omicron-predominant period. In response to fast-waning immunity and the threat of Omicron variant of concern (VOC) to healthcare workers (HCWs), we conduct a non-randomized trial (ChiCTR2200055564) in which 38 HCWs volunteer to receive a homologous booster of inactivated vaccines (BBIBP-CorV) 6 months after the 3rd dose. The primary and secondary outcomes are neutralizing antibodies (NAbs) and the receptor-binding domain (RBD)-directed antibodies, respectively. The 4th dose recalls waned immunity while having distinct effects on humoral responses to different antigens. The peak antibody response to the RBD induced by the 4th dose is inferior to that after the 3rd dose, whereas responses to the N-terminal domain (NTD) of spike protein are further strengthened significantly. Accordingly, the 4th dose further elevates the peak level of NAbs against ancestral SARS-CoV-2 and Omicron BA.2, but not BA.1 which has more NTD mutations. No severe adverse events related to vaccination are recorded during the trial. Here, we show that redistribution of immune focus after repeated vaccinations may modulate cross-protective immune responses against different VOCs.

Effect of Inactivated SARS-CoV-2 Vaccine on Thyroid Function and Autoimmunity Within 28 Days After the Second Dose.

Background: The safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is widely appreciated. However, there is limited knowledge regarding the potential impact of SARS-CoV-2 vaccines on the thyroid. Methods: We performed two prospective clinical trials between April and June, 2021, enrolling recipients of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV and CoronaVac). Thyroid function, antithyroid antibody levels, and SARS-CoV-2 neutralizing antibody levels were detected for each participant before receiving the first vaccine dose and 28 days after receiving the second vaccine dose. Results: A total of 657 recipients participated in the study. The overall median thyroid function and levels of antithyroid antibodies before and after SARS-CoV-2 vaccination were within the normal range. Among the 564 participants with normal thyroid function at baseline, 36 (6.38% [confidence interval; CI 4.51-8.73]) developed thyroid dysfunction. Of the 545 recipients with negative antithyroid antibodies at baseline, none developed abnormal antibodies after vaccination. Notably, 75.27% (70/93 [CI 65.24-83.63]) of the 93 recipients with thyroid dysfunction returned to normal function after vaccination. The levels of antithyroid peroxidase antibody (96.20% [CI 89.30-99.21]) and antithyroglobulin antibody (TgAb; 88.31% [CI 78.97-94.51]) remained positive after vaccination in most patients with abnormal values at baseline. However, the TgAb levels in more than half of the patients (48/77) decreased. All of 11 abnormal thyrotropin receptor antibody levels at baseline decreased postvaccination. Conclusions: Vaccination with an inactivated SARS-CoV-2 vaccine had no significant adverse impact on thyroid function or antithyroid antibodies within the first 28 days after the second dose. Clinical Trial Registration: ChiCTR2100045109 and ChiCTR2100042222.

Profile analysis of circRNAs in human THP-1 derived macrophages infected with intracellular Staphylococcus aureus.

BACKGROUND: Intracellular Staphylococcus aureus (S. aureus) infection is generally persistent, recurrent and difficult to treat due to the poor availability of antibiotics within macrophages cells and the lack of ideal diagnostic markers. Circular RNAs (circRNAs), with covalently closed circular structures, exists in the serum stably and is not easily degraded by nucleases. Besides, circRNAs play a pivotal in the eukaryotic regulation of genes expression and served as biomarkers in variety disease including microbial infections. However, the function of host circRNAs in intracellular S. aureus infection remains largely unclear. METHODS: In this study, the circRNAs expression profile was investigated by RNA sequencing technology in both S. aureus-infected THP-1 derived macrophages and mock control cells. The differentially expressed circRNAs (DE circRNAs) with a fold-change >1.5 (p < 0.05) are analyzed using functional pathway clustering prediction. Then, RT-qPCR was performed to verify the top 2 up-regulated circRNAs in the THP-1 cell and human serum samples so as to evaluate the value of circRNAs for S. aureus diagnosis. RESULTS: An intracellular survival THP-1 derived macrophages model of S. aureus infection was established. A total of 5,299 circRNAs were identified in human THP-1 derived macrophages infected with intracellular S. aureus. There were 61 DE circRNAs with a fold-change >1.5 (p < 0.05) after S. aureus infection. Among them, 22 circRNAs were up-regulated while 39 circRNAs down-regulated. GO and KEGG pathway analysis demonstrated that DE circRNAs were enriched in the processes such as Neurotrophin, Pyruvate metabolism and Notch signaling pathway. Moreover, hsa_circ_0000311 and chr13:43500472-43544806-(novel) were verified to be significantly upregulated in THP-1 derived macrophages and human serum samples between two groups. Finally, the networks of circRNA-miRNA-mRNA based on these two circRNAs were constructed respectively. CONCLUSION: Our study provides the first profile analysis of host circRNAs involved in intracellular S. aureus infection, which may serve as biomarkers for S. aureus diagnosis and contribute to the understanding of S. aureus evasion mechanisms.