Correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension.

OBJECTIVE: To explore the correlation between pulmonary vascular performance and hemodynamics in patients with pulmonary arterial hypertension (PAH), using right heart catheterization (RHC) and intravascular ultrasound (IVUS). METHOD: A total of 60 patients underwent RHC and IVUS examinations. Of these, 27 patients were diagnosed with PAH associated with connective tissue diseases (PAH-CTD group), 18 patients were diagnosed with other types of PAH (other-types-PAH group), and 15 patients were without PAH (control group). The hemodynamics and morphological parameters of pulmonary vessels in PAH patients were assessed using RHC and IVUS. RESULTS: There were statistically significant differences in right atrial pressure (RAP), pulmonary artery systolic pressure (sPAP), pulmonary artery diastolic pressure (dPAP), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) values between the PAH-CTD group, other-types-PAH group, and the control group (P < .05). No statistically significant difference was noticed in pulmonary artery wedge pressure (PAWP) and cardiac output (CO) values between these three groups (P > .05). The mean wall thickness (MWT), wall thickness percentage (WTP), pulmonary vascular compliance, dilation, elasticity modulus, stiffness index ß, and other indicators were significantly different between these three groups (P < .05). Pairwise comparison showed that the average levels of pulmonary vascular compliance and dilation in PAH-CTD group and other-types-PAH group were lower than those in control group, while the average levels of elastic modulus and stiffness index ß were higher than those in control group. CONCLUSION: Pulmonary vascular performance deteriorates in PAH patients, and the performance is better in PAH-CTD patients than in other types of PAH.

Distinct contact scaling effects in MoS2 Transistors revealed with asymmetrical contact measurements.

Two-dimensional (2D) semiconducting materials have great potential for use in future electronics due to their atomically thin nature enabling better scalability. The channel scalability of 2D materials has been thoroughly investigated, confirming their resilience to short-channel effects. However, the current understanding of contact scaling in 2D devices is inconsistent and oversimplified. Here we combine physically scaled contacts and asymmetrical contact measurements (ACMs) to investigate the contact scaling behavior in 2D field-effect transistors (FETs). The ACMs directly compare electron injection at different contact lengths while using the exact same MoS2  channel, eliminating channel-to-channel variations. Compared to devices with long contact lengths, devices with short contact lengths (scaled contacts) exhibit larger variations, 15% lower drain currents at high drain-source voltages, and a higher chance of early saturation and negative differential resistance. Quantum transport simulations show that the transfer length of Ni-MoS2  contacts can be as short as 5 nm. Importantly, our results suggest that scaled source contacts can limit the drain current, whereas scaled drain contacts do not. Furthermore, we clearly identify that the actual transfer length depends on the quality of the metal-2D interface. The asymmetrical contact measurements demonstrated here will enable further understanding of contact scaling behavior at various interfaces. This article is protected by copyright. All rights reserved.

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma.

Background: Increasing evidence indicates a crucial role for N7-methylguanosine (m7G) methylation modification in human disease development, particularly cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. However, the role of m7G in sarcomas (SARC) has not been adequately evaluated. Materials and methods: Transcriptome and clinical data were gathered from the TCGA database for this study. Normal and SARC groups were compared for the expression of m7G-related genes (m7GRGs). The expression of m7GRGs was verified using real-time quantitative PCR (RT-qPCR) in SARC cell lines. Then, differentially expressed genes (DEGs) were identified between high and low m7GRGs expression groups in SARC samples, and GO enrichment and KEGG pathways were evaluated. Next, prognostic values of m7GRGs were evaluated by Cox regression analysis. Subsequently, a prognostic model was constructed using m7GRGs with good prognostic values by Lasso regression analysis. Besides, the relationships between prognostic m7GRGs and immune infiltration, clinical features, cuproptosis-related genes, and antitumor drugs were investigated in patients with SARC. Finally, a ceRNA regulatory network based on m7GRGs was constructed. Results: The expression of ten m7GRGs was higher in the SARC group than in the control group. DEGs across groups with high and low m7GRGs expression were enriched for adhesion sites and cGMP-PKG. Besides, we constructed a prognostic model that consists of EIF4A1, EIF4G3, NCBP1, and WDR4 m7GRGs for predicting the survival likelihood of sarcoma patients. And the elevated expression of these four prognostic m7GRGs was substantially associated with poor prognosis and elevated expression in SARC cell lines. Moreover, we discovered that these four m7GRGs expressions were negatively correlated with CD4+ T cell levels, dendritic cell level and tumor purity, and positively correlated with tumor mutational burden, microsatellite instability, drug sensitivity and cuproptosis-related genes in patients with sarcomas. Then, a triple regulatory network of mRNA, miRNA, and lncRNA was established. Conclusion: The current study identified EIF4A1, EIF4G3, NCBP1, and WDR4 as prognostic genes for SARC that are associated with m7G.These findings extend our knowledge of m7G methylation in SARC and may guide the development of innovative treatment options.

Progress and perspectives of perioperative immunotherapy in non-small cell lung cancer.

Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC.

Patient characteristics and procedural variables are associated with length of stay and hospital cost among unilateral primary total hip arthroplasty patients: a single-center retrospective cohort study.

BACKGROUND: Total hip arthroplasty (THA) is a successful treatment for many hip diseases. Length of stay (LOS) and hospital cost are crucial parameters to quantify the medical efficacy and quality of unilateral primary THA patients. Clinical variables associated with LOS and hospital costs haven't been investigated thoroughly. METHODS: The present study retrospectively explored the contributors of LOS and hospital costs among a total of 452 unilateral primary THA patients from January 2019 to January 2020. All patients received conventional in-house rehabilitation services within our institute prior to discharge. Outcome parameters included LOS and hospital cost while clinical variables included patient characteristics and procedural variables. Multivariable linear regression analysis was performed to assess the association between outcome parameters and clinical variables by controlling confounding factors. Moreover, we analyzed patients in two groups according to their diagnosis with femur neck fracture (FNF) (confine THA) or non-FNF (elective THA) separately. RESULTS: Among all 452 eligible participants (266 females and 186 males; age 57.05 ± 15.99 year-old), 145 (32.08%) patients diagnosed with FNF and 307 (67.92%) diagnosed with non-FNF were analyzed separately. Multivariable linear regression analysis revealed that clinical variables including surgery duration, transfusion, and comorbidity (stroke) among the elective THA patients while the approach and comorbidities (stoke, diabetes mellitus, coronary heart disease) among the confine THA patients were associated with a prolonged LOS (P < 0.05). Variables including the American Society of Anesthesiologists classification (ASA), duration, blood loss, and transfusion among the elective THA while the approach, duration, blood loss, transfusion, catheter, and comorbidities (stoke and coronary heart disease) among the confine THA were associated with higher hospital cost (P < 0.05). The results revealed that variables were associated with LOS and hospital cost at different degrees among both elective and confine THA. CONCLUSIONS: Specific clinical variables of the patient characteristics and procedural variables are associated the LOS and hospital cost, which may be different between the elective and confine THA patients. The findings may indicate that evaluation and identification of detailed perioperative factors are beneficial in managing perioperative preparation, adjusting patients' anticipation, decreasing LOS, and reducing hospital cost.

Ethnic Disparities in Risk Factors for Myopia among Han and Minority Schoolchildren in Shawan, Xinjiang, China.

SIGNIFICANCE: The ethnic differences in myopia rates, ocular dimensions, and risk factors between Han and non-Han schoolchildren observed in this study may help fill the knowledge gap about ethnic minorities and are important for China and other countries to address vision-related health inequalities among different ethnic groups. PURPOSE: This study aimed to investigate the risk factors of juvenile myopia and elucidate the disparities of risk factors among Han and non-Han school students in Xinjiang, China. METHODS: A population-based cross-sectional study of 876 schoolchildren from grades 1 to 9 was conducted in the Anjihai Middle School in Shawan, Xinjiang Uygur Autonomous Region, China. Visual acuity and ocular biometry were assessed, and personal information, including behavior, birth status, and familial factors, was collected using self-made standardized questionnaires. RESULTS: The myopia rate among students of Han ethnicity (50.5%) was the highest, followed by Hui (41.3%) and Uygur et al. (32.0%, P < .001). Similar patterns were observed for mean axial length. The mean axial lengths are 23.7, 23.4, and 23.3 mm, respectively ( P = .01). Overall, performing high-quality eye exercises, longer sleep duration, being born in summer, parental smoking, and consuming more food containing anthocyanins were all associated with a lower incidence of myopia. Meanwhile, Han ethnicity, intensive near task, bad eye habits, and myopic mothers were associated with higher odds of myopia. After adjusting for environmental influences pertaining to myopia, the variation in myopia prevalence between Han and Uygur et al. remained significant, whereas it changed to not significant between Han and Hui ethnicities. CONCLUSIONS: Significant disparities were found in the prevalence of myopia among various ethnic groups in Shawan, Xinjiang. Life habits, birth status, and familial factors may contribute to such variance and play different roles in the occurrence of juvenile myopia among various ethnicities.

Circular RNA circGlis3 protects against islet ß-cell dysfunction and apoptosis in obesity.

Pancreatic ß-cell compensation is a major mechanism in delaying T2DM progression. Here we report the abnormal high expression of circGlis3 in islets of male mice with obesity and serum of people with obesity. Increasing circGlis3 is regulated by Quaking (QKI)-mediated splicing circularization. circGlis3 overexpression enhances insulin secretion and inhibits obesity-induced apoptosis in vitro and in vivo. Mechanistically, circGlis3 promotes insulin secretion by up-regulating NeuroD1 and Creb1 via sponging miR-124-3p and decreases apoptosis via interacting with the pro-apoptotic factor SCOTIN. The RNA binding protein FUS recruits circGlis3 and collectively assemble abnormal stable cytoplasmic stress granules (SG) in response to cellular stress. These findings highlight a physiological role for circRNAs in ß-cell compensation and indicate that modulation of circGlis3 expression may represent a potential strategy to prevent ß-cell dysfunction and apoptosis after obesity.

Onshore wind farms do not affect global wind speeds or patterns.

The proportion of global electricity generated by wind is increasing. There are concerns that onshore wind farms may affect local winds and/or patterns, with impacts on local ecosystems. Global-scale evaluations of these impacts are lacking. To investigate this issue, we used TerraClimate and ERA5 datasets covering the years 1980-1999 to judge the impact of onshore wind farms on wind speeds (at 10 m and 100 m elevations) and their distribution patterns. Winds were compared in two periods approximately representing periods without (1980-1999) and with (2001-2020) large-scale wind farms in existence. The TerraClimate dataset shows that 10 m wind speeds decreased at wind farm locations, while the wind speed distribution patterns did not change significantly. However, in the densest wind farm areas, the 10 m wind speeds actually increased. Analysis of the ERA5 data showed no significant changes in 10 m and 100 m wind speeds or distribution patterns at wind farm locations. The influence of wind farms on local and global wind speeds was slight and far less than that of oceanic/atmospheric oscillations. In the long term, the potential for onshore wind farms to reduce global wind speeds or affect their distribution patterns is very small.

Wind farms dry surface soil in temporal and spatial variation.

Wind farms have been proved to have potential impact on the ecology. As an important ecological factor, soil moisture has a great impact on the ecosystem. Therefore, it is of great significance to explore the effect of wind farms on soil moisture. At present, the remote sensing data can be used to calculate the soil moisture of wind farm conveniently, but its spatial resolution is poor. Moreover, the measured soil moisture can't express the spatial difference. Therefore, through the effective combination of remote sensing data and measured data, this method can accurately judge the impact of wind farm on soil moisture. This method investigated wind farms located in the grasslands of China. Remote sensing images and field data were used to explore the area and extent of influence of wind farms on grassland soil moisture. We use Landsat images and field measurements to derive a linear relationship between the soil moisture and the TVDI, which was calculated based on the land surface temperature and NDVI, was developed in this work. The correlation was used to reverse spatial distribution map of soil moisture before and after the construction of wind farms. The diurnal and seasonal variation of the influence of the wind farm on the grassland soil moisture was also judged.•This method of combining measurement and remote sensing provides a reference for analysing the influence of wind farms on soil moisture.•This method can be used for reference to compare the meteorological factors of different wind directions before and after the construction of wind farms.

How titanium and iron are integrated into hematite to enhance the photoelectrochemical water oxidation: a review.

Hematite has been considered as a promising photoanode candidate for photoelectrochemical (PEC) water oxidation and has attracted numerous interests in the past decades. However, intrinsic drawbacks drastically lower its photocatalytic activity. Ti-based modifications including Ti-doping, Fe2O3/Fe2TiO5 heterostructures, TiO2 passivation layers, and Ti-containing underlayers have shown great potential in enhancing the PEC conversion efficiency of hematite. Moreover, the combination of Ti-based modifications with various strategies towards more efficient hematite photoanodes has been widely investigated. Nevertheless, a corresponding comprehensive overview, especially with the most recent working mechanisms, is still lacking, limiting further improvement. In this respect, by summarizing the recent progress in Ti-modified hematite photoanodes, this review aims to demonstrate how the integration of titanium and iron atoms into hematite influences the PEC properties by tuning the carrier behaviours. It will provide more cues for the rational design of high-performance hematite photoanodes towards future practical applications.

Short-Term Outcomes of Enhanced Recovery after Surgery (ERAS) for Ankle Fracture Patients: A Single-Center Retrospective Cohort Study.

OBJECTIVE: Enhanced recovery after surgery (ERAS) has been successfully adopted for the improvement of medical quality and efficacy in many diseases, but the effect thereof for ankle fracture patients can vary. The aim of the present study was to explore the short-term postoperative outcomes of ERAS among ankle fracture patients. METHODS: The present study was a retrospective cohort study conducted between January 2019 and May 2019. One hundred and sixty ankle fracture participations (58 males and 102 females, aged 41.71 ± 14.51 years) were included. The participants treated with open reduction and internal fixation were divided into two groups (non-ERAS vs. ERAS) depending on whether ERAS was applied. Postoperative outcomes included American Orthopedic Foot and Ankle Society (AOFAS) score, length of stay (LOS), hospital cost, complications, and consumption of opioids. To assess the association between the groups and outcomes, generalized estimating equation (GEE) modeling and multivariable linear regression analysis were performed. RESULTS: The average follow-up periods of the participations were 24 months postoperatively. No significant differences were detected between the non-ERAS group and ERAS group with respect to the demographic of patients in terms of gender, age, Danis-Weber classification of fracture, dislocation of ankle joint, and comorbidity (P > 0.05). Significant differences in terms of a higher AOFAS score were found in the ERAS group compared with the non-ERAS group (6.73, 95% CI, 5.10-8.37, p < 0.001) at 3 months postoperatively (PO3M) and (4.73, 95% CI, 3.02-6.45, p < 0.001) at 6 months postoperatively (PO6M). However, similar AOFAS scores were found at 12 months postoperatively (PO12M) (0.28, 95% CI, -0.32 to 0.89, P > 0.05) and at 24 months postoperatively (PO24M) (0.56, 95% CI, -0.07 to 1.19, P > 0.05). Additionally, the GEE analysis and group-by-time interaction of AOFAS score revealed that the ERAS protocol could facilitate faster recovery for ankle fracture patients, with higher PO3M and PO6M (both P < 0.05). At the same time, significant differences in terms of a shorter length of stay (-3.19, 95% CI, -4.33 to -2.04, P < 0.01) and less hospital cost (-6501.81, 95% CI, -10955.21 to -2048.42, P < 0.01) were found in the ERAS group compared with the non-ERAS group. CONCLUSION: By reducing LOS and hospital cost, the ERAS protocol might improve the medical quality and efficacy. The present study can provide a realistic evaluation and comparison of the ERAS protocol among ankle fracture patients, and ultimately guide clinical decision making.

Potential effects of teriparatide (PTH (1-34)) on osteoarthritis: a systematic review.

Osteoarthritis (OA) is a common and prevalent degenerative joint disease characterized by degradation of the articular cartilage. However, none of disease-modifying OA drugs is approved currently. Teriparatide (PTH (1-34)) might stimulate chondrocyte proliferation and cartilage regeneration via some uncertain mechanisms. Relevant therapies of PTH (1-34) on OA with such effects have recently gained increasing interest, but have not become widespread practice. Thus, we launch this systematic review (SR) to update the latest evidence accordingly. A comprehensive literature search was conducted in PubMed, Web of Science, MEDLINE, the Cochrane Library, and Embase from their inception to February 2022. Studies investigating the effects of the PTH (1-34) on OA were obtained. The quality assessment and descriptive summary were made of all included studies. Overall, 307 records were identified, and 33 studies were included. In vivo studies (n = 22) concluded that PTH (1-34) slowed progression of OA by alleviating cartilage degeneration and aberrant remodeling of subchondral bone (SCB). Moreover, PTH (1-34) exhibited repair of cartilage and SCB, analgesic, and anti-inflammatory effects. In vitro studies (n = 11) concluded that PTH (1-34) was important for chondrocytes via increasing the proliferation and matrix synthesis but preventing apoptosis or hypertrophy. All included studies were assessed with low or unclear risk of bias in methodological quality. The SR demonstrated that PTH (1-34) could alleviate the progression of OA. Moreover, PTH (1-34) had beneficial effects on osteoporotic OA (OPOA) models, which might be a therapeutic option for OA and OPOA treatment.

Antibacterial Activity of an FtsZ Inhibitor Celastrol and Its Synergistic Effect with Vancomycin against Enterococci In Vitro and In Vivo.

Enterococci can cause various infectious diseases, including urinary tract infection, wound infection, and life-threatening endocarditis and meningitis. The emergence and transmission of vancomycin-resistant enterococci (VRE) have presented a challenge to clinical treatment. There is an urgent need to develop new strategies to fight against this pathogen. This study investigated the antibacterial and anti-biofilm activity of celastrol (CEL), a natural product originating from Tripterygium wilfordii Hook F, against enterococci, and its adjuvant capacity of restoring the susceptibility of VRE to vancomycin in vitro and in vivo. CEL inhibited all enterococcus strains tested, with MICs ranging from 0.5 to 4 µg/mL. More than 50% of biofilm was eliminated by CEL at 16 µg/mL after 24 h of exposure. The combination of CEL and vancomycin showed a synergistic effect against all 23 strains tested in checkerboard assays. The combination of sub-MIC levels of CEL and vancomycin showed a synergistic effect in a time-kill assay and exhibited significant protective efficacy in Galleria mellonella larval infection model compared with either drug used alone. The underlying mechanisms of CEL were explored by conducting biomolecular binding interactions and an enzyme inhibition assay of CEL on bacterial cell-division protein FtsZ. CEL presented strong binding and suppression ability to FtsZ, with Kd and IC50 values of 2.454 µM and 1.04 ± 0.17 µg/mL, respectively. CEL exhibits a significant antibacterial and synergic activity against VRE in vitro and in vivo and has the potential to be a new antibacterial agent or adjuvant to vancomycin as a therapeutic option in combating VRE. IMPORTANCE The emergence and transmission of VRE pose a significant medical and public health challenge. CEL, well-known for a wide range of biological activities, has not previously been investigated for its synergistic effect with vancomycin against VRE. In the present study, CEL exhibited antibacterial activity against enterococci, including VRE strains, and restored the activity of vancomycin against VRE in vitro and in vivo. Hence, CEL has the potential to be a new antibacterial adjuvant to vancomycin and could provide a promising therapeutic option in combating VRE.

Omental cancer-associated fibroblast-derived exosomes with low microRNA-29c-3p promote ovarian cancer peritoneal metastasis.

Ovarian cancer (OC) is characterized by frequent widespread peritoneal metastasis. Cancer-associated fibroblasts (CAFs) represent a critical stromal component of metastatic niche and promote omentum metastasis in OC patients. However, the role of exosomes derived from omental CAFs in metastasis remains unclear. We isolated exosomes from primary omental normal fibroblasts (NFs) and CAFs from OC patients (NF-Exo and CAF-Exo, respectively) and assessed their effect on metastasis. In mice bearing orthotopic OC xenografts, CAF-Exo treatment led to more rapid intraperitoneal tumor dissemination and shorter animal survival. Similar results were observed in mice undergoing intraperitoneal injection of tumor cells. Among the miRNAs downregulated in CAF-Exo, miR-29c-3p in OC tissues was associated with metastasis and survival in patients. Moreover, increasing miR-29c-3p in CAF-Exo significantly weakened the metastasis-promoting effect of CAF-Exo. Based on RNA sequencing, expression assays, and luciferase assays, matrix metalloproteinase 2 (MMP2) was identified as a direct target of miR-29c-3p. These results verify the significant contribution of exosomes from omental CAFs to OC peritoneal metastasis, which could be partially due to the relief of MMP2 expression inhibition mediated by low exosomal miR-29c-3p.

Anterolateral approach may be superior to posterolateral approach in controlling postoperative lower limb discrepancy in primary total hip arthroplasty: A single-center, retrospective cohort study.

OBJECTIVES: This study aims to investigate the possible association and comparison between anterolateral approach (ALA) and posterolateral approach (PLA) and postoperative lower limb discrepancy (LLD) in selective total hip arthroplasty (THA). PATIENTS AND METHODS: April 2021 and July 2021, a total of 266 consecutive patients (126 males, 140 females; mean age: 46.7±13.6 years; range, 22 to 60 years) who underwent unilateral primary THA via the ALA or the PLA were retrospectively analyzed. The operations were performed by a single surgical team. All patients were divided into two groups according to the approach: ALA group (n=66) and PLA group (n=200). Relevant data were recorded. Diagnosis including hip osteoarthritis, developmental dysplasia of the hip (DDH), aseptic avascular necrosis (AVN), and inflammatory arthritis were noted. Perioperative follow-up radiographs were evaluated and measured to compare the postoperative LLD and offset. The association between two approaches and postoperative LLD and offset was analyzed using the univariate and multivariate linear regression analysis. RESULTS: The mean follow-up was 20±3.7 (range, 16 to 25) months. Univariate analysis revealed that the postoperative LLD, the postoperative acetabular offset, and hospital costs were lower in the ALA group than the PLA group (p<0.01). However, the offset and length of stay were comparable between the two groups (p>0.05). Multivariate analysis revealed that the PLA (ß=4.71; 95% confidence interval [CI]: 1.78 to 7.64), preoperative LLD (ß=0.29; 95% CI: 0.21 to 0.37), DDH (ß=5.01; 95% CI: 1.47 to 8.55), and AVN (ß=3.81; 95% CI: 0.50 to 7.12) were the main contributors to the postoperative LLD. CONCLUSION: Our study results suggest that the ALA may be superior to the PLA in controlling the postoperative LLD among some of the selective unilateral primary THA patients. Both the ALA and the PLA were comparable in terms of the restoration of offset.

Value of magnetic resonance imaging and sialography of the parotid gland for diagnosis of primary Sjögren syndrome.

AIM: To evaluate the utility of magnetic resonance imaging (MRI) and magnetic resonance sialography (MRS) for diagnosis of primary Sjögren syndrome (pSS) singly or integrated with 2016 American College of Rheumatology (ACR)/European League Against Rheumatic Diseases (EULAR) classification criteria. METHODS: The diagnostic efficiencies of MRI, MRS, and labial salivary gland biopsy (LSGB) were evaluated. The prediction model was established by multivariate analysis. Finally, performance of the ACR/EULAR criteria was evaluated after addition of MRI + MRS or replacement of original items by MRI + MRS. RESULTS: The combined use of LSGB + MRI + MRS provided the greatest diagnostic value. MRI and MRS grade had positive correlations with disease duration and pathological grade of the labial gland (both P < 0.001). MRI and MRS grade had positive correlations with xerostomia severity and negative correlations with unstimulated salivary flow rate (both P < 0.001). The consistency of MRI grade and MRS grade in the diagnosis of parotid gland lesions was poor (κ = 0.253, P < 0.001). The diagnostic efficiency of our prediction model (AUC 0.906) was similar to that of criteria from the ACR/EULAR (AUC 0.930). Adding MRI + MRS to the ACR/EULAR criteria improved the sensitivity (92.3% vs 90.8%), whereas the specificity remained the same (88.9% vs 89.1%). Replacing LSGB by MRI + MRS in the ACR/EULAR criteria decreased both sensitivity and specificity (88.1% vs 90.8% and 86.4% vs 89.1%, respectively). CONCLUSION: The combined application of MRI and MRS has ideal clinical application value in the diagnosis of early-stage pSS. Validity of the ACR/EULAR criteria remains high after incorporation of MRI + MRS.

Tumour-derived exosomal piR-25783 promotes omental metastasis of ovarian carcinoma by inducing the fibroblast to myofibroblast transition.

Ovarian carcinoma inherently possesses a distinct metastatic organotropism for the adipose-rich omentum, contributing to disease progression. Although the premetastatic microenvironment (PMM) has been known to often play a prometastatic role during the process, incomplete mechanistic insight into PMM formation has prevented its therapeutic targeting. Omental fibroblasts can be activated by tumour cells to differentiate into myofibroblasts, termed the fibroblast-to-myofibroblast transition (FMT), which, in turn, enhances cancer aggressiveness. Here, we report crosstalk between cancer cells and omental fibroblasts through exosomal piR-25783, which fuels tumour metastasis. Tumour cell-secreted exosomal piR-25783 activates the TGF-ß/SMAD2/SMAD3 pathway in fibroblasts and promotes the FMT in the omentum along with the secretion of various cytokines and elevation of proliferative, migratory, and invasive properties, contributing to the formation of PMMs. Furthermore, piR-25783-induced myofibroblasts promote tumour implantation and growth in the omentum. In addition, the overexpression of piR-25783 in ovarian carcinoma is associated with unfavourable clinicopathological characteristics and shorter survival. In this study, we provide molecular, functional, and translational evidence suggesting that exosomal piR-25783 plays an important role in the formation of PMMs and the development of metastatic diseases in vitro and in vivo and may serve as a potential therapeutic target for ovarian carcinoma with metastasis.

Teriparatide ameliorates articular cartilage degradation and aberrant subchondral bone remodeling in DMM mice.

Objective: Knee osteoarthritis (KOA) is a highly prevalent musculoskeletal disorder characterized by degeneration of cartilage and abnormal remodeling of subchondral bone (SCB). Teriparatide (PTH (1-34)) is an effective anabolic drug for osteoporosis (OP) and regulates osteoprotegerin (OPG)/receptor activator of nuclear factor ligand (RANKL)/RANK signaling, which also has a therapeutic effect on KOA by ameliorating cartilage degradation and inhibiting aberrant remodeling of SCB. However, the mechanisms of PTH (1-34) in treating KOA are still uncertain and remain to be explored. Therefore, we compared the effect of PTH (1-34) on the post-traumatic KOA mouse model to explore the potential therapeutic effect and mechanisms. Methods: In vivo study, eight-week-old male mice including wild-type (WT) (n â€‹= â€‹54) and OPG-/- (n â€‹= â€‹54) were investigated and compared. Post-traumatic KOA model was created by destabilization of medial meniscus (DMM). WT mice were randomly assigned into three groups: the sham group (WT-sham; n â€‹= â€‹18), the DMM group (WT-DMM; n â€‹= â€‹18), and the PTH (1-34)-treated group (WT-DMM â€‹+ â€‹PTH (1-34); n â€‹= â€‹18). Similarly, the OPG-/- mice were randomly allocated into three groups as well. The designed mice were executed at the 4th, 8th, and 12th weeks to evaluate KOA progression. To further explore the chondro-protective of PTH (1-34), the ATDC5 chondrocytes were stimulated with different concentrations of PTH (1-34) in vitro. Results: Compared with the WT-sham mice, significant wear of cartilage in terms of reduced cartilage thickness and glycosaminoglycan (GAG) loss was detected in the WT-DMM mice. PTH (1-34) exhibited cartilage-protective by alleviating wear, retaining the thickness and GAG contents. Moreover, the deterioration of the SCB was alleviated and the expression of PTH1R/OPG/RANKL/RANK were found to increase after PTH (1-34) treatment. Among the OPG-/- mice, the cartilage of the DMM mice displayed typical KOA change with higher OARSI score and thinner cartilage. The damage of the cartilage was alleviated but the abnormal remodeling of SCB didn't show any response to the PTH (1-34) treatment. Compared with the WT-DMM mice, the OPG-/--DMM mice caught more aggressive KOA with thinner cartilage, sever cartilage damage, and more abnormal remodeling of SCB. Moreover, both the damaged cartilage from the WT-DMM mice and the OPG-/--DMM mice were alleviated but only the deterioration of SCB in WT-DMM mice was alleviated after the administration of PTH (1-34). In vitro study, PTH (1-34) could promote the viability of chondrocytes, enhance the synthesis of extracellular matrix (ECM) (AGC, COLII, and SOX9) at the mRNA and protein level, but inhibit the secretion of inflammatory cytokines (TNF-α and IL-6). Conclusion: Both wear of the cartilage was alleviated and aberrant remodeling of the SCB was inhibited in the WT mice, but only the cartilage-protective effect was observed in the OPG-/- mice. PTH (1-34) exhibited chondro-protective effect by decelerating cartilage degeneration in vivo as well as by promoting the proliferation and enhancing ECM synthesis of chondrocytes in vitro. The current investigation implied that the rescue of the disturbed SCB is dependent on the regulation of OPG while the chondro-protective effect is independent of modulation of OPG, which provides proof for the treatment of KOA. The translational potential of this article: Systemic administration of PTH (1-34) could exert a therapeutic effect on both cartilage and SCB in different mechanisms to alleviate KOA progression, which might be a novel therapy for KOA.