Group 3 innate lymphoid cells promotes Th17 cells differentiation in rheumatoid arthritis.

OBJECTIVES: To investigate the correlation between innate lymphoid cell (ILC) subsets with T-helper (Th) cells and to explore the effect of ILCs on T cells in rheumatoid arthritis (RA). METHODS: We analysed the frequencies of ILC subsets in RA patients with varying disease activity and their correlation with Th cell subsets. We further investigated this correlation in various organs of collagen-induced arthritis (CIA) mice. The effects of ILCs on CD4+ T cells were determined by in vitro cell co-culture experiments. RESULTS: ILCs were less frequent in RA patients than in healthy controls, with higher levels of group 3 ILCs (ILC3s) in RA (p<0.05). ILC3s correlated positively with Th1 and Th17 cells in RA peripheral blood (p<0.05). In the peripheral blood, spleen, and lymph nodes of CIA, ILC3s decreased and then increased during arthritis progression. ILC3s correlated positively with Th1 and Th17 cells in the spleen and lymph nodes of CIA (p<0.05). NKp46+ ILC3s in the spleen positively correlated with Th1 and Th17 cells (p<0.05). Under Th17 cell differentiation conditions, co-culturing CIA-derived ILC3s directly with naive CD4+ T cells promoted Th17 differentiation and increased IL-17 secretion. However, co-culturing through a transwell insert impeded Th17 differentiation without affecting IL-17 secretion. CONCLUSIONS: ILC3s positively correlated with Th1 and Th17 cells in RA. In CIA, the frequencies of ILC3s changed with disease development and showed a positive correlation with Th1 and Th17 cells. ILC3s may facilitate the differentiation of Th17 cells through direct cell-cell contact.

Postoperative perineal hernia repair: what is the evidence?

The present study determined the characteristics of perineal hernia treatment in the literature, and the incidence of postoperative recurrence was stratified according to repair techniques. A systematic search of the available literature on the treatment of postoperative perineal hernias was performed using a major database. The types of repair techniques and outcome were entered into an electronic database and a pooled analysis was performed. A total of 213 cases of postoperative perineal hernia repair were collected from 20 relevant articles in the literature after excluding case reports (n < 3). Synthetic mesh was the material used most frequently for perineal hernia repair (55.9%). The most frequently used approach in perineal hernia repair was the perineal approach (56.5%). The recurrence rate was highest with the use of biological mesh (40.4%) and the perineal approach (35.6%). The recurrence rate was lowest in the combined abdominal & perineal approach (0%), followed by the abdominal approach (8.8%) and the laparoscopic approach (11.8%). A number of different repair techniques have been described in the literature. The use of synthetic mesh via a combined abdominal-perineal approach or intraabdominal/laparoscopic approach was shown to be associated with a reduced postoperative recurrence rate.

A retrospective cohort study in Chinese patients with adult polymyositis and dermatomyositis: risk of comorbidities and subclassification using machine learning.

OBJECTIVES: To identify the risk factors in Chinese patients with adult polymyositis and dermatomyositis for their comorbidities and explore a subclassification system. METHODS: Clinical records of 397 patients with idiopathic inflammatory myopathies were retrospectively reviewed. Logistic regression was used to identify potential risk factors for interstitial lung disease (ILD), other rheumatic diseases, and malignancy after bivariate analysis. Hierarchical clustering and decisional tree were utilised to identify subgroups and explore a subclassification system. RESULTS: A total of 119 polymyositis and 191 dermatomyositis patients were included. Anti-PM/Scl, anti-Ro52, anti-aminoacyl-tRNA synthetase and anti-MDA5 (adjusted odds ratios (AOR)=4.779, 1.917, 5.092 and 7.714 respectively) antibodies were risks (p<0.05), whereas overlapping malignancy was protective (AOR=0.107; p=0.002) for ILD across polymyositis, dermatomyositis and the total group. In subgroup models, Raynaud's phenomenon, arthralgia and semi-quantitative anti-nuclear antibody (AOR=51.233, 4.261, 3.047 respectively) were risks for other overlapping rheumatic diseases (p<0.05). For overlapping malignancy, male and anti-TIF1γ antibodies (AOR=2.533, 16.949) were risks (p<0.05), whereas disease duration and combination of ILD (AOR=0.954, 0.106) were protective in the total group (p<0.05); while anti-NXP2 antibodies were identified as risk factors (AOR=73.152; p=0.038) in polymyositis. Hierarchical clustering suggested a subclassification with 6 subgroups: malignancy overlapping dermatomyositis, classical dermatomyositis, polymyositis with severe muscle involvement, dermatomyositis with ILD, polymyositis with ILD, and overlapping of myositis with other rheumatic diseases. CONCLUSIONS: Accompanying ILD, other rheumatic diseases and malignancy are strongly associated with clinical manifestation and myositis-specific or myositis-associated autoantibodies among Chinese polymyositis and dermatomyositis patients. The subclassification system proposed a more precise phenotype defining toward stratified treatments.

Monocytic MDSCs skew Th17 cells toward a pro-osteoclastogenic phenotype and potentiate bone erosion in rheumatoid arthritis.

OBJECTIVES: While myeloid-derived suppressor cells (MDSCs) were previously shown to promote a proinflammatory T helper (Th) 17 response in autoimmune conditions, a potential impact of the MDSC-Th17 immune axis on abnormal bone destruction in RA remains largely unknown. METHODS: We investigated the correlation between the frequency of MDSCs or its subsets and joint destruction in RA patients. The reciprocal actions of patient-derived MDSCs and Th17 cells were studied using osteoclast (OC) differentiation and bone resorption assays in vitro, which were further validated using mouse models of RA. Contribution of MDSCs to osteoclastogenesis and bone erosion in vivo was determined by depletion or transfer of MDSCs. RESULTS: Human MDSCs, particularly monocytic MDSCs (M-MDSCs), exhibit inherent OC-differentiating capacity and positively correlate with clinical bone erosion in RA patients. Strikingly, patient-derived M-MDSCs can program Th17 cells towards a pro-osteoclastogenic phenotype, which in return potentiates OC differentiation via the receptor activator of nuclear factor κΒ ligand (RANK-L)-RANK signalling. This enhanced osteolysis driven by the reciprocal actions of M-MDSCs and Th17 cells is further confirmed using mouse models of RA. Selective depletion of M-MDSCs significantly ameliorates osteoclastogenesis and disease severity in arthritic mice, whereas transfer of M-MDSCs aggravates bone erosion associated with increased OCs in recipient mice. CONCLUSION: Our findings highlight the functional plasticity of MDSCs and identify a novel pro-osteoclastogenic pathway governed by interplay between myeloid cells and T lymphocytes in autoimmune RA.

KIAA1429 regulates cell proliferation by targeting c-Jun messenger RNA directly in gastric cancer.

N6-methyladenosine (m6A) modification regulatory proteins are involved in the development of many types of cancer. KIAA1429 serves as a scaffold in bridging the catalytic core components of the m6A methyltransferase complex. The role of KIAA1429 in gastric cancer and its related mechanism has not been reported upon. The expression of KIAA1429 was detected in human gastric cancer tissues and cell lines by quantitative real-time polymerase chain reaction and western blot. The effects of KIAA1429 on gastric cancer proliferation were evaluated by cell counting kit assays, colony formation assays, flow cytometry assay, and in vivo experiments with nude mice. And messenger RNA (mRNA) high-throughput sequencing, RNA immunoprecipitation assay (RIP), luciferase assay, and a rescue experiment were used to identify the relationship between KIAA1429 and its specific targeted gene, c-Jun. We found that KIAA1429 was upregulated in gastric cancer tissues, and expressed lower in adjacent tissues. The upregulated KIAA1429 promoted proliferation and downregulated KIAA1429 was proved to inhibit proliferation of gastric cancer in vitro and in vivo. Then, we identified the potential KIAA1429 regulating gene as c-Jun by mRNAs high-throughput sequencing and RIP assay. By luciferase assay, we verified that KIAA1429 regulated the expression of c-Jun in an m6A-independent manner. Finally, the overexpression of c-Jun rescued the inhibition of proliferation caused by KIAA1429 knockdown in gastric cancer cells. KIAA1429 could act as an oncogene in gastric cancer by stabilizing c-Jun mRNA in an m6A-independent manner. This highlights the functional role for KIAA1429 as a potential prognostic biomarker and therapeutic target in gastric cancer.

Impact of body fat location and volume on incisional hernia development and its outcomes following repair.

BACKGROUND: Obesity is known to increase the likelihood of developing abdominal wall hernias, body mass index (BMI) alone does not provide detailed information about the amount and location of body fat. The aim of this study was to investigate the link between various adipose tissue parameters and the incidence of incisional hernias (IHs), as well as the outcomes of hernia repair. METHODS: We conducted a comprehensive review of the existing literature to examine the relationship between various body fat parameters and the occurrence of IHs after abdominal surgeries, as well as the outcomes of hernia repair. RESULTS: Thirteen studies were included for analysis. Eight trials evaluated the IH development after abdominal surgeries via specific fat parameters, and five studies evaluated the postoperative outcomes after IH repair. The findings of this study suggest that an increase in visceral fat volume (VFA or VFV) and subcutaneous fat (SFA or SFV) are linked to a higher incidence of IHs after abdominal surgeries. Higher levels of VFV or VFA were associated with more challenging fascia closure and greater postoperative recurrence rates following repair. Whereas BMI did not demonstrate a significant association. CONCLUSION: Measuring visceral and subcutaneous fat composition preoperatively can be a useful tool for assessing the risk of IH, and is more reliable than BMI. Elevated levels of these fat parameters have been linked to increased recurrence of IH following hernia repair, as well as the use of complex surgical techniques during repair.

Effects of Personality and Behavioral Syndromes on Competition for Social Hierarchical Status in Anemonefish Amphiprion clarkii.

In this study, the behavioral ethogram of Amphiprion clarkii during the growth phase prior to sexual differentiation was summarized based on behavioral observations in three social environments. These behaviors can be classified into four categories: in addition to normal behaviors, the other three categories of behaviors-threatening, agonistic, and appeasing behaviors-represent different intentions in interactions with other individuals. Subsequently, the personalities of each individual were assessed by testing their reactions to intruders. These individuals mainly exhibited two distinct personality types: bold-aggressive and shy-submissive. In pairing experiments, the interactive behaviors of the anemonefish were observed in pairing combinations of different body sizes and personalities. The impact of personality on the establishment of a stable social hierarchy was confirmed by significant differences in the success rates of different pairing combinations, with the frequency of appeasing behaviors being the main factor influencing the success rate. Our results suggested that in natural waters, when juvenile individuals migrate among host anemones, shy-submissive individuals are more likely to be accepted due to their appeasing behaviors towards larger individuals, thus avoiding the risk of being attacked and bitten, and benefiting the survival of the individual. Conversely, bold-aggressive individuals are more likely to be driven away to another host anemone due to their unwillingness to settle for a lower-ranked status, thereby contributing to population dispersal and increasing opportunities for gene exchange between populations.

Chromosome-level genome assembly and annotation of the Spinibarbus caldwelli.

Spinibarbus caldwelli is an important freshwater economic fish in China. Owing to uncontrolled fishing, wild resources of S. caldwelli have decreased rapidly and may be on the verge of extinction. In this study, utilizing single-molecule real-time (SMRT) sequencing technology and chromatin interaction mapping (Hi-C) technologies, we assembled the first chromosome-scale genome for S. caldwelli about 1.77 Gb in size, with a contig N50 length of 11.83 Mb and scaffold N50 length of 33.91 Mb. In total 1.72 Gb (97.01%) of the contig sequences were anchored onto fifty chromosomes with the longest scaffold being 56.20 Mb. Furthermore, proximately 49.41% of the genome was composed of repetitive elements. In total, 49,377 protein-coding genes were predicted, of which 47,724 (96.65%) genes have been functionally annotated. The high-quality chromosome-level reference genome and annotation are vital for supporting basic genetic studies and will be contribute to genetic structure, functional elucidation, evolutionary inquiry, and germplasm conservation for S. caldwelli.

Stability of population genetic structure in large yellow croaker (Larimichthys crocea): Insights from temporal, geographical factors, and artificial restocking processes.

Despite concerns about overfishing and the potential impact of release programs on wild populations, our study of 3116 individuals from 13 wild populations and 2787 individuals from two cultured populations in Zhejiang and Fujian provinces spanning 2008 to 2023 reveals a relatively stable genetic diversity in Larimichthys crocea. Surprisingly, the genetic diversity of wild large yellow croaker populations has remained consistent over the years, suggesting minimal influence from population declines due to overfishing. With the exception of populations in Sansha Bay and Luoyuan Bay, no significant genetic differences were observed among wild populations, indicating a single panmictic genetic population across the East and South China seas. Notably, significant genetic differentiation exists between cultured and wild populations, suggesting a possible limited genetic adaptation of cultured-released individuals to the wild environment. The genetic differences observed between the Sansha Bay, with its adjacent Luoyuan Bay populations, and other wild populations underscore the dual effects of habitat environment and farming activities on the genetic structure of large yellow croaker. Our findings suggest that, despite declines in population numbers due to overfishing and expands extensive cultured releases, the genetic diversity of L. crocea populations remains largely unaffected. Moreover, the L. crocea population along the Chinese coast appears to form a single panmictic population with considerable genetic diversity.

DKK-1 and Its Influences on Bone Destruction: A Comparative Study in Collagen-Induced Arthritis Mice and Rheumatoid Arthritis Patients.

Dickkopf-1 (DKK-1) has been considered a master regulator of bone remodeling. As precursors of osteoclasts (OCs), myeloid-derived suppressor cells (MDSCs) were previously shown to participate in the process of bone destruction in rheumatoid arthritis (RA). However, the role of DKK-1 and MDSCs in RA is not yet fully understood. We investigated the relevance between the level of DKK-1 and the expression of MDSCs in different tissues and joint destruction in RA patients and collagen-induced arthritis (CIA) mouse models. Furthermore, the CIA mice were administered recombinant DKK-1 protein. The arthritis scores, bone destruction, and the percentage of MDSCs in the peripheral blood and spleen were monitored. In vitro, the differentiation of MDSCs into OCs was intervened with recombinant protein and inhibitor of DKK-1. The number of OCs differentiated and the protein expression of the Wnt/ß-catenin signaling pathway were explored. The level of DKK-1 positively correlates with the frequency of MDSCs and bone erosion in RA patients and CIA mice. Strikingly, recombinant DKK-1 intervention significantly exacerbated arthritis scores and bone destruction, increasing the percentage of MDSCs in the peripheral blood and spleen in CIA mice. In vitro experiments showed that recombinant DKK-1 promoted the differentiation of MDSCs into OCs, reducing the expression of ß-catenin and TCF4 and increasing the expression of CyclinD1. In contrast, the DKK-1 inhibitor had the opposite effect. Our findings highlight that DKK-1 promoted MDSCs expansion in RA and enhanced the differentiation of MDSCs into OCs via targeting the Wnt/ß-catenin pathway, aggravating the bone destruction in RA.

Important Role of the Ihh Signaling Pathway in Initiating Early Cranial Remodeling and Morphological Specialization in Cromileptes altivelis.

In this study, we identified the important contribution of frontal bone remodeling in shaping the 'sunken head and humpback' appearance in C. altivelis. Our investigation identified a developmental milestone at a total length of 5-6 cm, making the onset of its morphologic specialization in this species. A comparative analysis with closely related species reveals heightened activity in the frontal osteoblasts of the humpback grouper, potentially providing a physiological basis for its remodeling. Furthermore, our findings highlight that a significant upregulation in the expression levels of Ihhb, Ptch1, and Gli2a genes was seen in C. altivelis within the specified developmental stage, indicating an important involvement of the Ihhb-Ptch1-Gli2a signaling pathway in initiating the morphological specialization. We hypothesized that Ihh signaling could be attributed to shifts in mechanical stress, resulting from muscle traction on the frontal bone due to changes in swimming patterns during development. This study not only offers significant insights into unraveling the molecular mechanisms that govern phenotypic specialization and ecological adaptations in the humpback grouper but also serves as a valuable reference for studies on fishes with a controversial morphology and molecular phylogeny.

Piezo1 activation accelerates osteoarthritis progression and the targeted therapy effect of artemisinin.

INTRODUCTION: Osteoarthritis (OA) is a devastating whole-joint disease affecting a large population worldwide with no cure; its mechanism remains poorly defined. Abnormal mechanical stress is the main pathological factor of OA. OBJECTIVES: To investigate the effects of Piezo1 activation on OA development and progression and to explore Piezo1-targeting OA treatment. METHODS: The expression levels of Piezo1 were determined in human OA cartilage and experimental OA mice. Mice with genetic Piezo1 deletion in chondrocytes or intra-articular injection of the Piezo1 activator Yoda1 were utilized to determine the effects on DMM-induced OA progression. Effects of artemisinin (ART), a potent antimalarial drug, on Piezo1 activation, chondrocyte metabolism and OA lesions were determined. RESULTS: Piezo1 expression was elevated in articular chondrocytes in human OA and DMM-induced mouse OA cartilage. Piezo1 deletion in chondrocytes largely attenuates DMM-induced OA-like phenotypes. In contrast, intra-articular injection of Yoda1 aggravates the knee joint OA lesions in mice. PIEZO1 activation increases, while PIEZO1 siRNA knockdown decreases, expression of RUNX2 and catabolic enzymes MMP13 and ADAMTS5 in primary human articular chondrocytes in a PI3K-AKT dependent manner. We have provided strong evidence supporting that ART is a novel and potent inhibitor of Piezo1 activation in primary OA-HACs and all cell lines examined, including human endothelial HUVEC cells, ATDC5 chondrocyte-like cells and MLO-Y4 osteocytes-like cells. Results from in vitro experiments confirmed that ART decreases the Yoda1-induced increases in the levels of OA-related genes and p-PI3K and p-AKT proteins in OA-HACs and alleviates DMM-induced OA lesions in mice. CONCLUSIONS: We establish a critical role of Piezo1 in promoting OA development and progression and define ART as a potential OA treatment.

Association of Exercise With Vascular Function in Patients With CKD: A Meta-Analysis of Randomized Controlled Trials.

Background and Aim: Vascular function is associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Whether exercise improves vascular function in such patients remains controversial. This study aimed to conduct a meta-analysis on the effect of exercise training on the vascular function of patients with CKD. Methods: Embase, the Cochrane Central Register of Controlled Trials, and Medline were searched from inception until November 15, 2021. The terms exercise, CKD, dialysis, kidney transplant, and randomized controlled trial (RCT) were searched alone or in combination. RCTs were included when studies compared exercise with active control, usual care, or no intervention, and the studies reported vascular function on patients with CKD. Results: This meta-analysis included 18 RCTs with 817 patients. Exercise training was significantly associated with decreased pulse wave velocity weighted mean difference (WMD), -0.56; 95% confidence interval (CI), -1.02 to -0.09, P = 0.02 and augmentation index (WMD, -3.26; 95% CI, -5.46 to -1.05, P = 0.004). It was also significantly associated with improved peak VO2 (WMD, 2.64; 95% CI, 1.94-3.35, P < 0.00001), general health (WMD, 7.03; 95% CI, 0.65-13.42, P = 0.03), and vitality (WMD, 9.1; 95% CI, 2.50-15.69, P = 0.007). Conclusions: The meta-analysis suggested that exercise training improved vascular function in patients with CKD. An exercise program should be considered as one of the management strategies for vascular dysfunction in patients with CKD. Further studies are needed to demonstrate that exercise training improves cardiovascular diseases in patients with CKD.

The Comparison of eTEP and IPOM in Ventral and Incisional Hernia Repair: A Systematic Review and Meta-analysis.

BACKGROUND: Open sublay technique and laparoscopic intraperitoneal onlay mesh (IPOM) technique are the most common used procedures in ventral and incisional hernia repair, however, each technique has its own disadvantages. The enhanced view total extraperitoneal technique (eTEP) aims to put the mesh in the retromuscular space by minimal invasive technique. This study is to investigate the efficacy and safety of eTEP and IPOM approach in ventral and incisional hernia repair. METHODS: The major databases (PubMed, Embase, Springer, and Cochrane Library) were searched, and all studies published through May 1, 2021, using the keywords "enhanced view extraperitoneal," "extended view totally extraperitoneal," "eTEP," "TEP," "laparoscopic retromuscular," "ventral hernia," "incisional hernia," "laparoscopic intraperitoneal onlay mesh," "IPOM." All relevant articles and reference lists in these original studies were also obtained from the above databases. RESULTS: Five trials containing 433 patients were included in the present study. Compared with the IPOM technique, the eTEP ventral/incisional hernia repair was associated a longer operative time [mean difference=44.79; 95% confidence interval (CI): 26.57, 63; P=0.00001], less acute pain on postoperative day 1 (standardized mean difference=-3.90; 95% CI: -4.42, -3.38; P<0.00001), and day 7 (standardized mean difference=-3.72; 95% CI: -6.09, 1.35; P=0.002), and the eTEP group had a shorter hospital stay compared with the IPOM group (mean difference=-0.56; 95% CI: -0.74, -0.39; P=0.00001). There was no significant difference concerning the incidence of seroma, hematoma, intraoperative complication, and postoperative ileus between eTEP and IPOM groups. CONCLUSIONS: The eTEP technique in ventral and incisional hernia repair shows significantly lower acute postoperative pain and shorter hospital study but a longer operative time. In addition, there is no significant difference in terms of intraoperative or postoperative complications. Further randomized controlled studies with long-term follow-up are needed to evaluate the eTEP technique.

Statins Have an Anti-Inflammation in CKD Patients: A Meta-Analysis of Randomized Trials.

Background: Persistent inflammation has been recognized as an important comorbid condition in patients with chronic kidney disease (CKD) and is associated with many complications, mortality, and progression of CKD. Previous studies have not drawn a clear conclusion about the anti-inflammatory effects of statins in CKD. This meta-analysis is aimed at assessing the anti-inflammatory effects of statins therapy in patients with CKD. Methods: A comprehensive literature search was conducted in these databases (Medline, Embase, Cochrane library, and clinical trials) to identify the randomized controlled trials that assess the anti-inflammatory effects of statins. Subgroup, sensitivity, and trim-and-fill analysis were conducted to determine the robustness of pooled results of the primary outcome. Results: 25 eligible studies with 7921 participants were included in this meta-analysis. The present study showed that statins therapy was associated with a decreased C-reactive protein (CRP) (-2.06 mg/L; 95% CI: -2.85 to -1.27, p < 0.01). Subgroup, sensitivity, and trim-and-fill analysis showed that the pooled results of CPR were stable. Conclusion: This meta-analysis demonstrates that statins supplementation has anti-inflammatory effects in patients with CKD. Statins exert an anti-inflammatory effect that is clinically important in improving complications, reducing mortality, and slowing progression in CKD. We believe that the benefits of statins to CKD are partly due to their anti-inflammatory effects. However, stains usually are prescribed in the CKD patients with dyslipidemia, whether statins can reduce inflammation in CKD patients with normal serum lipid needed to explore in the future. Therefore, we suggest that randomized clinical trials need to assess the effect of statins in CKD patients with normal serum lipid. Whether statins can be prescribed for aiming to inhibit inflammation in CKD also needed further study. Trial Registration. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42022310334.

Transabdominal Partial Extraperitoneal Repair of Lateral Hernias of the Abdomen and Flank.

Background: Lateral hernia (LH) repair is a challenging and debated topic in abdominal wall surgery because of the anatomical location and mesh placement and fixation. Large LHs should be managed with an open procedure; however, there is no consensus regarding the repair of small- to medium-sized LHs. We report our treatment of this type of LH using the transabdominal partial extraperitoneal (TAPE) technique. Methods: After retrospective review of the prospective hernia database at two hernia centers, patients with small- to medium-sized LHs who underwent the TAPE technique were identified and analyzed. The key components of our technique include wide dissection of peritoneum off the defect and use of that peritoneum to cover the lower and medial part of the mesh as much as possible. The parameters studied included patient demographics, intraoperative data, and postoperative outcome. Results: We studied 19 patients with small- to medium-sized LHs repaired using the TAPE procedure between 2017 and 2020. LH etiologies were primary hernia (n = 3), incisional hernia (n = 15), and traumatic hernia (n = 1). Mean defect size was 5.8 ± 2.1 cm (range 2.5-10 cm), mean operative time 118.1 ± 41.7 minutes (range 65-240 minutes), and mean postoperative stay 6.4 ± 2.0 days (range 6-9 days). There were no perioperative complications. At a mean follow-up of 20 months, no patient had recurrence of LH. Discussion: For small- to medium-sized LHs, the laparoscopic TAPE technique is minimally invasive and safe; the procedure is associated with minimal postoperative complications.

Natural Killer Cells Infiltration in the Joints Exacerbates Collagen-Induced Arthritis.

Introduction: The role of natural killer (NK) cells in rheumatoid arthritis remains controversial. We aimed to assess the role of NK cells in the pathogenesis of rheumatoid arthritis. Materials and Methods: The percentage of NK cells in the peripheral blood, spleen, lymph nodes and inflamed paws from collagen-induced arthritis mice were examined through the disease progression. Correlation between the proportion of NK cells and subsets with arthritis score, histopathological changes, and bone destruction were evaluated. Adoptive cell transfer was performed to determine the effect of NKp46+NK cells on arthritis development, and the role of receptor NKp46 was explored with NKp46 knockout mice. Results: The percentage of NK cells in peripheral blood decreased at the late stage of the disease and negatively correlated with arthritis score. NK cells increased in the inflamed paws during arthritis development and were positively associated with arthritis score, histopathological change, and bone destruction. Adoptive transfer of NKp46+NK cells before disease onset resulted in increased NK cells infiltration in the joints, higher incidence of arthritis, more severe clinical symptoms, and more pronounced joint inflammation and bone damage. NKp46 deficiency had no significant influence on the incidence and severity of arthritis in collagen-induced arthritis mice. Conclusions: NK cell infiltration in the joints positively correlates with arthritis progression, inflammation, and bone destruction. The pathogenic role of NK cells in rheumatoid arthritis may be independent of the receptor NKp46.

Paclitaxel Inhibits Synoviocyte Migration and Inflammatory Mediator Production in Rheumatoid Arthritis.

Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis and progression of rheumatoid arthritis (RA). It is urgent to develop new drugs that can effectively inhibit the abnormal activation of RA-FLS. In our study, the RA-FLS cell line, MH7A, and mice with collagen-induced arthritis (CIA) were used to evaluate the effect of paclitaxel (PTX). Based on the results, PTX inhibited the migration of RA-FLS in a dose-dependent manner and significantly reduced the spontaneous expression of IL-6, IL-8, and RANKL mRNA and TNF-α-induced transcription of the IL-1 ß, IL-8, MMP-8, and MMP-9 genes. However, PTX had no significant effect on apoptosis in RA-FLS. Mechanistic studies revealed that PTX significantly inhibited the TNF-α-induced phosphorylation of ERK1/2 and JNK in the mitogen-activated protein kinase (MAPK) pathway and suppressed the TNF-α-induced activation of AKT, p70S6K, 4EBP1, and HIF-1α in the AKT/mTOR pathway. Moreover, PTX alleviated synovitis and bone destruction in CIA mice. In conclusion, PTX inhibits the migration and inflammatory mediator production of RA-FLS by targeting the MAPK and AKT/mTOR signaling pathways, which provides an experimental basis for the potential application in the treatment of RA.

[Study on the extraction of breviscapine from Erigeron breviscapus with ultrasonic wave technology optimized by central composite design-response surface method].

OBJECTIVE: To evaluate the effectiveness of ultrasound-assisted extraction and establish the optimized extraction conditions of breviscapine from Erigeron breviscapus. METHODS: On the basis of the single factor and according to the central composite design principles (CCD), the response surface method (RSM) with 3 factors and 3 levels was adopted and the independent variables were ultrasonic wave extracting time, ethanol concentration, and the ratio of solvent volume to Erigeron breviscapus mass, breviscapine extraction yield determinated by HPLC was used as response value. RESULTS: Ultrasonic wave extracting time of 24.5 min, ethanol concentration of 74.7% and the ratio of solvent volume to Erigeron breviscapus mass of 19.8 (mL/g) were selected as optimum conditions. Regression coefficients of binomial fitting complex model was 0. 9549 and the predicted breviscapine extraction yield was 0.641%, while the actual extraction yield was 0.632% (n = 5), with relative error of -1.14%. CONCLUSION: This study confirms the efficiency of ultrasound-assisted extraction as a simple, inexpensive and effective method to improve the extraction of breviscapine from Erigeron breviscapus. The observed and predicted values are close to each other, which proves that the optimization of supersonic extraction process of breviscapine from Erigeron breviscapus by CCD-RSM is reasonable and successful.

Intraoperative Observation during Total Extraperitoneal Repair (TEP).

We aim to observe and dissect the essential anatomical landmarks in totally extraperitoneal (TEP) procedures. Forty-six TEP procedures in 30 patients were prospectively performed in our department. During the dissection of the preperitoneal space, the following distances between landmarks were measured. D1: the distance from pubic symphysis to the arcuate line in the midline; D2: the distance from the inferior epigastric artery to the lateral border of the arcuate line (before sharp incision was performed); D3: as in D2 (but after sharp incision was performed); D4: the distance from the inferior epigastric artery to the crossing site of vas deferens and obliterated umbilical artery. Furthermore, the morphology of the posterior rectus sheath was documented. The corresponding distance between the anatomical landmarks varied greatly in each individual. D1: 8 ± 1.6 cm (range 4-10 cm). D2: 4.9 ± 0.8 cm (3.5-7 cm). D3: 6.8 ± 0.9 cm (5-9 cm). D4: 6.1 ± 1 cm (4.8-8.5 cm). Complete rectus sheath was found in 30.4 per cent (14/46) of the hernias. Anatomical variations were common in preperitoneal space. The crossing site of vas deferens and obliterated umbilical artery can serve as a landmark for dissection. Complete rectus was present in one-third of hernias, which necessitates a sharp incision for entering the correct lateral preperitoneal space.