COVID-19 vaccination and infection status: a cross-sectional survey of patients with rheumatic diseases in China.

To evaluate the vaccination status and clinical practice of patients with rheumatic diseases (RD) during the COVID-19 pandemic in China and to explore the impact of vaccination on infection severity in patients with RD. A cross-sectional survey was conducted among RD patients in outpatient and inpatient settings of the Rheumatology and Immunology Department in our hospital. Participants' characteristics, vaccination status, COVID-19 infection status, and medication for acute COVID-19 were collected. A total of 749 valid surveys were included in the study. A total of 271 (36.2%) patients were not vaccinated, and 478 (63.8%) patients received at least one dose of COVID-19 vaccine. 83.3% of patients were vaccinated with inactivated vaccines. Several patients with RD experienced the disease flare (57, 11.9%) and some adverse reactions (31, 6.5%) after COVID-19 vaccination. The COVID-19 infection rate was 84.1% in our study, which was not reduced by vaccination. However, vaccinated patients with RD showed decreased frequencies of pneumonia and hospitalization, compared with those of unvaccinated patients. Independent factors associated with hospitalization were COVID-19 vaccination (OR = 0.422, 95% CI 0.227-0.783), advanced age (OR = 1.070, 95% CI 1.046-1.095), ILD (OR = 1.245, 95% CI 1.082-1.432), and glucocorticoid (OR = 4.977, 95% CI 2.326-10.647). Adverse reactions to vaccines and disease flare are not common in RD patients. Although COVID-19 vaccination could not reduce the risk of COVID-19 infection in RD patients, it may effectively decrease the frequencies of pneumonia and hospitalization after infection. It is recommended that patients with RD should receive COVID-19 vaccination if there are no contraindications because the benefits outweigh the risks.

Effect of intravenous anesthetic drugs on fertilization rate in oocyte retrieval.

BACKGROUND: The purpose of this study was to investigate the effects of intravenous anesthetic drugs on fertilization rate in subjects receiving oocyte retrieval by assisted reproduction technology (ART). METHODS: A retrospective cohort study was designed. The clinical information of subjects who received oocyte retrieval procedure was collected. The subjects were divided into two groups based on the type of anesthesia used: the no-anesthesia group and the intravenous anesthesia group. Propensity score matching (PSM) was performed and multiple linear regression analyses were conducted. Fertilization rate was compared between the two groups before and after PSM. RESULTS: A total of 765 subjects were divided into two groups: the no-anesthesia group (n = 482) and the intravenous anesthesia group (n = 283). According to propensity scores, 258 pairs of subjects were well matched, and the baseline data between the two groups were not significantly different (P > 0.05). Fertilization rate was 77% in the intravenous anesthesia group, and 76% in the no-anesthesia group, without significant between-group difference (P = 0.685). Before matching, Poisson regression analysis showed no effect of intravenous anesthetic drugs on fertilization rate (RR = 0.859, 95%CI: 0.59 to 1.25, P = 0.422). After matching, no difference was found either (RR = 0.935, 95%CI: 0.67 to 1.29, P = 0.618). CONCLUSION: Intravenous anesthetic drugs may exert no effects on fertilization rate in subjects receiving ART.

Impedance spectroscopy for identifying tau protein to monitor anesthesia-based issues.

Anesthesia-related drugs cause various side effects and health-related illnesses after surgery. In particular, neurogenerative disorder is a common problem of anesthesia-related drugs. A patient gets anesthesia as a requirement of the preoperative evaluation to diagnose the medical illness, which is caused by anesthetic drug treatment. Different blood-based biomarkers help in identifying the changes appearing in patients after anesthesia treatment. Among them, tau protein is a sensitive biomarker of neurodegenerative diseases, and the fluctuations in tau proteins are highly associated with various diseases. Furthermore, researchers have found unstable levels of tau protein after the anesthesia process. The current research has focused on quantifying tau protein via impedance spectroscopy to identify the problems caused by anesthesia-related drugs. An impedance spectroscopy electrode was modified into a multiwalled carbon nanotube, and an amine-ended aptamer was then attached. This electrode surface was used to quantify the tau protein level and reached the detection limit of 1 fM. The determination coefficient was found to be y = 369.93x + 1144.9, with R2 = 0.9846 in the linear range of 1 fM-1 nM. Furthermore, tau protein spiked human serum was clearly identified on the immobilized aptamer surface, indicating the specific detection.

Infection with Opportunistic Bacteria Triggers Severe Pulmonary Inflammation in Lupus-Prone Mice.

Infection is a common cause of hospitalization and mortality in patients with systemic lupus erythematosus (SLE). How the underlying immune dysfunctions affect the antimicrobial immunity remains largely unknown. In the present study, employing the pulmonary infection model, we determined the antimicrobial defence of lupus-prone mice. After infecting with opportunistic bacterium Haemophilus influenzae (Hi), lupus-prone mice (B6/lpr) exhibited inefficient bacterial elimination and recovered slowly. They generated severer inflammation at the early stage of infection, as excessive accumulation of neutrophils and enhanced production of proinflammatory cytokines were observed in the lung. In addition, a large number of apoptotic cells were detected in the lungs of B6/lpr mice. For adaptive immune responses, B6/lpr mice were capable to generate enough protective Hi-specific Th17 cells. They evoked stronger Hi-specific γδ T17 response in both lungs and spleens. Unexpectedly, both CD4 and γδ T cells from lupus-prone mice showed deficiency in IFN-γ production. For humoral immune responses, compared with those of WT mice, the concentrations of Hi-specific IgA, IgM, and IgG, especially IgG, were significantly higher in the B6/lpr mice. Our findings suggest that lupus mice are capable to generate antibacterial immune responses; however, the overwhelming inflammation and overactivated immune responses increase the severity of infection.

Mesenchymal stem cells induced CD4+ T cell apoptosis in treatment of lupus mice.

Umbilical cord-derived mesenchymal stem cell transplantation (UCMSCT) has been used to treat human autoimmune diseases like lupus for example, but little is known about its effect on cell apoptosis. Here we evaluated the efficacy of UCMSCT for lupus treatment and explored the mechanism by which mesenchymal stem cells (MSCs) modulate T cell apoptosis in lupus mice. 1 × 106 human umbilical cord-derived mesenchymal stem cells (UC-MSCs) were injected into B6.MRL-Faslpr (B6.lpr) mice via tail vein. 6 h, 24 h or 4 weeks later, the mice were sacrificed and the apoptosis of lymphocytes in peripheral blood and spleen were detected by flow cytometry. The immune cell subpopulations in spleen were also measured at 6 h and 24 h, respectively. The therapeutic effects were assessed after 4 weeks. The frequency of peripheral blood CD4+ T cell apoptosis was reduced in lupus-prone B6.lpr mice. UCMSCT alleviated the disease phenotypes in B6.lpr mice, decreased the ratio of Th1 as well as Th2 cells, and increased percentages of apoptotic CD4+ T cells in vivo and vitro. Collectively, our findings unravel that UCMSCT alleviate lupus disease and reverse immune imbalance possibly by promoting T cell apoptosis in B6.lpr mice.

Comparable therapeutic potential of umbilical cord mesenchymal stem cells in collagen-induced arthritis to TNF inhibitor or anti-CD20 treatment.

OBJECTIVES: The effects of mesenchymal stem cell (MSC) transplantation on established collagen-induced arthritis (CIA) were evaluated and compared to biologic therapies. METHODS: CIA was induced with the immunisation of type II collagen (CII) in DBA/1 mice. Human umbilical cord MSC, anti-TNF antibody, rhTNFR:Fc fusion protein and anti-CD20 antibody were respectively injected intraperitoneally into CIA mice. Arthritis severity was assessed by clinical and histological scoring. The frequencies of lymphocytes in spleen were analysed, and serum concentrations of cytokines and autoantibody to CII were also measured. The ability of MSC to regulate the balance of T helper cell subsets in CII stimulated CIA CD4+ T cells was assessed in vitro. RESULTS: MSC treatment significantly decreased the severity of arthritis, which was comparable to biologic treatments. All the treatments down-regulated Th1 subset. Except anti-CD20 all the treatments decreased Th17 subset. MSC treatment enhanced the proportion of regulatory T (Treg) cells and inhibited the generation of T follicular helper (Tfh) cells. The decrease in autoantibody level was detectable in all the treated groups. In vitro MSC induced Foxp3+ T cells, and down-regulated IL-17+, IFNγ+ T cells and pathogenic IL-17+IFNγ+ or IL-17+Foxp3+ T cells. MSC also reduced the secretion of IL-1ß, IL-6, IL-17 and TNF-α among collagen-specific T cells. CONCLUSIONS: MSC show comparable effects to the known biologic treatments and correct immune imbalance in CIA. MSC might provide a promising approach for the treatment of rheumatoid arthritis.

Mesenchymal stem cells promote CD206 expression and phagocytic activity of macrophages through IL-6 in systemic lupus erythematosus.

Human umbilical cord-derived mesenchymal stem cells (UCMSCs) show therapeutic effects on systemic lupus erythematosus (SLE). Deficiency in functional polarization and phagocytosis in macrophages has been suggested in the pathogenesis of SLE. We found that macrophages from B6.MRL-Fas(lpr) mice exhibited lower level of CD206, the marker for alternatively activated macrophage (AAM, also called M2). In addition, the phagocytic activity of B6.MRL-Fas(lpr) macrophages was also decreased. UCMSC transplantation improved the proportion of CD206(+) macrophages and their phagocytic activity in B6.MRL-Fas(lpr) mice. Importantly, macrophages from SLE patients also showed lower expression of CD206 and reduced phagocytic activity, which were corrected by being co-cultured with UCMSCs in vitro and in SLE patients receiving UCMSC transplantation. Mechanistically, we demonstrated that IL-6 was required for the up-regulation of CD206 expression and phagocytic activity of UCMSC-treated SLE macrophages. Our results indicate that UCMSCs alleviate SLE through promoting CD206 expression and phagocytic activity of macrophages in an IL-6 dependent manner.

Effect of adenosine triphosphate-sensitive potassium activation on peripheral and central pain sensitization.

BACKGROUND: Alterations in adenosine triphosphate-sensitive potassium (KATP) activity and expression under changing physiological conditions are important adaptive and protective mechanisms. KATP subunit expression is also altered in neuropathic pain; whether these changes are adaptive or deleterious is unclear. We therefore established a skin/muscle incision and retraction (SMIR) rat model of postoperative pain and examined the relationship between pain sensitization and changes in KATP subunit expression. METHODS: Rats were randomly divided into untreated, sham-operation, SMIR, and SMIR + Pinacidil (sulfonylurea receptor [SUR]2-activator) groups. In the SMIR group, skin and muscle were retracted for 1 h after incision. In the SMIR + Pinacidil group, Pinacidil was injected intraperitoneally 0.5 h before SMIR or into the spinal myelin sheath 7 d after SMIR. Mechanical withdrawal threshold was used as an index of pain sensitivity. Expression levels and localization of the KATP subunits Kir6.2, Kir6.1, SUR1, and SUR2 were measured by Western blotting and immunofluorescence. RESULTS: A rat postoperative pain model was successfully established, in which SMIR induced mechanical hypersensitivity (allodynia). Notably, significantly increased Kir6.1, Kir6.2, SUR1, and SUR2 protein expression levels were observed in tissues around the incision (P < 0.05). In addition, significantly decreased Kir6.1, SUR2, and SUR1 protein levels were obtained in spinal cord L3-L5. SMIR also starkly increased nerve growth factor expression in the muscle around the incision. Importantly, intrathecal Pinacidil injection inhibited the overexpression of allodynia markers and nerve growth factor. CONCLUSIONS: Hyperexcitability due to spinal Kir6.1 and SUR2 downregulation may be responsible for postoperative pain. SUR2 activation is a potential strategy to inhibit postoperative allodynia.

Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases.

The impact of the Coronavirus disease 2019 (COVID-19) pandemic on autoimmune diseases (AID) patients has been an important focus. This study was undertaken to characterize the incidence, clinical manifestations and hospitalization among AID affected by COVID-19 and to analyze the association between immunomodulatory medication and these outcomes. Clinical, demographic, maintenance treatment, symptoms and disease course data and outcomes of AID patients with COVID-19 infection were assessed via an online survey tool and printed copy from 1 January till February 28, 2023. A total of 432 patients with AID were enrolled in the study. The results showed the most common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was hydroxychloroquine (HCQ). The usage of csDMARDs didn't increase the risk of COVID-19 infection. Patients who warranted hospitalization were significantly older. ILD was associated with higher hospitalization rate. No csDMARDs other than calcineurin inhibitor (CNI) was associated with increased risk of hospitalization. HCQ intake was associated with cough. Compared with no glucocorticoids (GCs) group, high doses of GCs were accompanied with higher proportion of gastrointestinal symptoms and tachycardia, lower proportion of sore throat and ageusia. GCs didn't provoke the COVID-19 infection in patients with AID, but chronic use of oral GCs was significantly more common in those requiring hospitalization, and higher dose of GCs were correlated with higher risk of hospitalization. 97 patients discontinued csDMARDs after infection, which resulted in an elevated risk of hospitalization. Meanwhile, withdrawal of csDMARDs was associated with higher odds of disease flare and lower proportion of remission than maintenance groups. Collectively, our analysis provides the evidence that maintenance treatment of csDMARDs may be more prudent for AID patients during COVID-19 pandemic.

Dyslipidemia is associated with inflammation and organ involvement in systemic lupus erythematosus.

INTRODUCTION: Disturbed lipid metabolism was observed in systemic lupus erythematosus (SLE) patients. This study aimed to evaluate the relationships between dyslipidemia and visceral organ involvement, disease severity, inflammatory factors, and drug intake in SLE patients. METHOD: Inpatients with SLE (n = 105) and healthy controls (HC) (n = 75) were recruited in this study. Clinical and laboratory data were collected from patient records. The concentrations of tumor necrosis factor receptors superfamily member1A (TNFRSF1A), member1B (TNFRSF1B) and adipokine angiopoietin-like 4 (ANGPTL4) in plasma were measured by ELISA. RESULT: Compared to HC, serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and apolipoprotein B (ApoB) were significantly increased, while high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) were decreased in SLE patients. Patients with higher disease activity and renal damage suffered from more severe dyslipidemia. Renal functional parameters were closely correlated with serum lipid levels. Inflammatory factors were associated with dyslipidemia. The levels of TNFRSF1A and TNFRSF1B were obviously increased and associated with kidney involvement in SLE patients. Patients with high-dose glucocorticoid intake showed more severe dyslipidemia. CONCLUSIONS: Attention should be paid to the dyslipidemia of SLE. Dyslipidemia is associated with inflammation and organ involvement in SLE. These findings might provide a new strategy for the treatment of SLE. Key Points • Serum levels of TG, TC, LDL, and ApoB were significantly increased, while HDL and ApoA1 were decreased in SLE patients. • Patients with higher disease activity and renal damage suffered from more severe dyslipidemia. Renal functional parameters and inflammatory factors were closely correlated with serum lipid levels. • Patients with high-dose glucocorticoid intake showed more severe dyslipidemia. • These findings might provide a new strategy for the treatment of SLE.

Umbilical cord mesenchymal stem cells alleviate Sjögren's syndrome and related pulmonary inflammation through regulating Vγ4+ IL-17+ T cells.

Background: Since gamma delta (γδ) T cells are involved in various autoimmune diseases, we aimed to verify whether γδ T cells participate in the pathogenesis of Sjögren's syndrome (SS) and related pulmonary inflammation, and also aimed to evaluate the effects of umbilical cord mesenchymal stem cells (MSCs) on SS-related pulmonary inflammation and the γδ T cells. Methods: The saliva flow rates of female non-obese diabetic (NOD/Ltj) mice were measured. Histopathologic analysis was performed in salivary glands (SG) and lung tissues. The levels of γδ T cells and their subsets in the peripheral blood, spleen, and lung were examined by flow cytometry. The purified γδ T cells were adoptively transferred into NOD/Ltj mice. MSC transplantation was performed in 8-week-old NOD/Ltj mice. Results: The results showed lymphocytic infiltration in SG and lacrimal glands (LG), and reduction of saliva flow rates in 8-week NOD/Ltj mice. The levels of γδ T cells decreased in peripheral blood, but increased in the lung of 8- and 12-week-old NOD/Ltj mice. The proportions and numbers of Vγ4+ T cells and Vγ4+ IL-17A+ T cells increased in the lung, but decreased in peripheral blood of 8-week-old NOD/Ltj mice. Notably, transfer of γδ T cells decreased the rate of saliva flow, as well as aggravated the pathological changes in the lung. The transplantation of MSCs increased saliva flow rate and alleviated pathological injury in the SG and lung. The frequencies of Vγ4+ T cells and Vγ4+ IL-17A+ T cells in the lung and spleen significantly decreased after MSC treatment. Our results demonstrated that γδ T cells and Vγ4+ T cells contribute to the pathogenesis of SS and SS-related pulmonary inflammation. In addition, MSCs relieved SS and SS-related pulmonary inflammation through suppressing Vγ4+ IL-17A+ T cells. Conclusions: Peripheral Vγ4+ T cells infiltrate into the lung in SS mice, and aggravate the symptoms of SS and SS-related pulmonary inflammation by secreting IL-17A. Meanwhile, lymphocyte infiltration could be reversed by MSC transplantation, which indicates the potential of MSCs in the treatment of SS and SS-related pulmonary inflammation patients.

Delayed inhibition of ERK and p38 attenuates neuropathic pain without affecting motor function recovery after peripheral nerve injury.

Peripheral nerve injuries (PNIs) often result in persistent neuropathic pain, seriously affecting quality of life. Existing therapeutic interventions for PNI-induced neuropathic pain are far from satisfactory. Extracellular signal-regulated kinases (ERKs) and p38 have been found to participate in triggering and maintaining PNI-induced neuropathic pain. However, ERK and p38 also contribute to axonal regeneration and motor function recovery after PNI, making it difficult to inhibit ERK and p38 for therapeutic purposes. In this study, we simultaneously characterized neuropathic pain and motor function recovery in a mouse sciatic nerve crush injury model to identify the time window for therapeutic interventions. We further demonstrated that delayed delivery of a combination of ERK and p38 inhibitors at three weeks after PNI could significantly alleviate PNI-induced neuropathic pain without affecting motor function recovery. Additionally, the combined use of these two inhibitors could suppress pain markedly better than either inhibitor alone, possibly reducing the required dose of each inhibitor and alleviating the side effects and risks of the inhibitors when used individually.

Lidocaine inhibits the proliferation and metastasis of epithelial ovarian cancer through the Wnt/ß-catenin pathway.

BACKGROUND: Lidocaine, an amide local anesthetic, has recently been found to have anticancer action in various cancer cells. However, the role of lidocaine in epithelial ovarian cancer (EOC) remains largely unknown. In the present study, we investigated how lidocaine regulates the progression of EOC. METHODS: Real-time polymerase chain reaction was used to examine the expression of Snail, Wnt, ß-catenin, E-cadherin, vimentin, matrix metalloproteinase (MMP)-7, MMP-9, and vascular endothelial growth factor in lidocaine-treated cells. Cell proliferation assays, cell apoptosis assays, and cell migration assays were employed to verify the function of lidocaine in EOC cells. Cell proliferation and cell migration assays were employed to verify the function of Wnt/ß-catenin signaling in lidocaine-treated EOC cells together with Wnt-overexpressing plasmids or inhibitor NVP-XAV939. RESULTS: Lidocaine could inhibit proliferation, migration, and invasion, and induce apoptosis in ovarian cancer cells lines in a dose-dependent manner. Wnt/ß-catenin signaling was involved in the suppression of epithelial-mesenchymal transition progression of ovarian cancer cells, which resulted in the downregulation of Snail and vimentin, as well as the upregulation of E-cadherin. Furthermore, overexpressed Wnt could reverse the carcinostatic effect of lidocaine, while Wnt inhibitor XAV-939 synergistically enhanced the antitumor effect of lidocaine. CONCLUSIONS: Mechanistically, lidocaine could inhibit the proliferation and metastasis of EOC by the Wnt/ß-catenin pathway to regulate the progression of EOC.

Exchange proteins directly activated by cyclic adenosine monophosphate inhibitor reverses mechanical allodynia via the modification of astrocytes activity in the spinal cord.

BACKGROUND: Gliosis and inflammation are pivotal in the development of acute and chronic pain. Here, we demonstrated a previously unidentified molecular mechanism in which the activation of exchange proteins directly activated by cyclic adenosine monophosphate (Epac)1 accelerated the activation of astrocytes in the spinal cord, thereby promoting chronic postsurgical pain (CPSP). METHODS: We established a rat model of CPSP induced by skin/muscle incision and retraction (SMIR). Pain behaviors were assessed using mechanical withdrawal threshold (MWT) at different times. The lumbosacral enlargement of the spinal cord was isolated to detect the expression of Epac1 and the activity of astrocytes. They were assessed using western blot and immunofluorescence staining. RESULTS: SMIR induced persistent mechanical hyperalgesia after surgery. This hyperalgesia response was prolonged to more than 21 d after surgery. The time course of spinal Epac1 upregulation was correlated with SMIR-induced pain behaviors. Meanwhile, Epac1 immunoreactivity was colocalized primarily with astrocytes but not with microglial cells or neurons on 7 d after surgery. Intrathecal injection of Epac1 inhibitor CE3F4 significantly suppressed SMIR-induced mechanical allodynia and activation of astrocytes in the spinal cord. This analgesic effect of single-dose administration of CE3F4 lasted up to 6 h and wore off at 12 h after injection. CONCLUSIONS: Spinal Epac1-mediated activation of astrocytes may facilitate CPSP. Inhibition of Epac1 may effectively prevent CPSP.

Role of caveolin-1 in chronic postsurgical pain in rats.

Chronic postsurgical pain (CPSP) has a high incidence, but the underlying mechanisms remain elusive. Previous studies have indicated that caveolin-1 (Cav-1) plays a notable role in pain modulation. To study the role of Cav-1 in CPSP in the present study, a rat model of skin/muscle incision and retraction (SMIR) was established. Under anesthesia, skin and superficial muscle of the medial thigh were incised and a small pair of retractors inserted. It was revealed that SMIR increased the expression of Cav-1 in the dorsal root ganglion (DRG) and the injured tissue around the incision. Furthermore, the infiltration of endothelial cells and macrophages in the injured tissue around the incision increased constantly, and the vascular permeability increased due to the destruction of the vascular endothelial barrier function around the injured tissue. Cav-1 was mainly expressed by CD68-positive macrophages and CD34-positive endothelial cells in the injured tissues around the incision, while it was also primarily localized in the medium and large neurofilament 200-positive neurons and a small number of calcitonin gene-related peptide- and isolectin B4-positive small and medium-sized neurons in the DRG. The results demonstrated that the sustained high expression levels of Cav-1 in the injured tissue around the incision could lead to the dysfunction of the vascular endothelial barrier and, thus, could induce the inflammatory response through the lipoprotein transport of endothelial cells, thereby resulting in peripheral sensitization. In addition, the sustained high expression levels of Cav-1 in the DRG could sensitize large-sized neurons and change the transmission mode of noxious stimuli. The findings of the present study indicated that a Cav-1-mediated process could participate in neuronal transmission pathways associated with pain modulation.

Mesenchymal Stem Cells Enhance Pulmonary Antimicrobial Immunity and Prevent Following Bacterial Infection.

BACKGROUND: Immunosuppressants such as cyclophosphamide (CTX) have been employed to treat a wide array of autoimmune diseases. The most unfavourable side effects of these drugs are their suppression on the antimicrobial immunity and increasing the risk of infection. As a promising substitution/adjunct, mesenchymal stem cells (MSCs) are currently being tested in several clinical trials. However, their influence on the recipients' antimicrobial immunity remains unclear. METHODS: In this study, C57BL/6 mice were treated with either CTX or MSCs, and then both the innate and adaptive immunity of the lung were determined. To investigate the influence of CTX and MSCs on the immune defence against infection, the treated mice were intranasally infected with opportunistic pathogen Haemophilus influenzae (Hi). Bacterial clearance and antibacterial immune responses were analysed. RESULTS: Our data showed that CTX strongly inhibited the proliferation of lung immune cells, including alveolar macrophages (AMs) and T cells, whereas MSCs increased the numbers of these cells. CTX suppressed the phagocytic activity of AMs; on the contrary, MSCs enhanced it. Notably, infusion of MSCs led to a remarkable increase of regulatory T cells and Th1 cells in the lung. When infected by Hi, CTX did not significantly impair the elimination of invaded bacteria. However, MSC-treated mice exhibited accelerated bacterial clearance and moderate inflammation and tissue damage. CONCLUSION: Our study reported that unlike traditional immunosuppressants, modulation of MSCs on the recipient's immune response is more elegant. It could preserve and even enhance the antimicrobial defence, suggesting that MSCs are better choice for patients with high risk of infection or those who need long-term immunosuppressive regimen.

Effects of nicorandil on p120 expression in the spinal cord and dorsal root ganglion of rats with chronic postsurgical pain.

Chronic postsurgical pain (CPSP) has a high incidence, but the underlying mechanism is not well understood. Accumulating evidence has suggested that central sensitization is the main mechanism of pain. To study the role of p120 in CPSP, a skin/muscle incision and retraction (SMIR) model was established, and immunofluorescence staining and western blotting were performed to analyze the expression of p120 in the spinal cord and dorsal root ganglion (DRG). The results demonstrated that SMIR increased the expression of p120 in the DRG and the spinal cord compared with the naive group. Furthermore, it was demonstrated that p120 was mainly distributed in the glial fibrillary acidic protein­positive astrocytes in the spinal cord, and in the neurofilament 200­positive medium and large neurons in the DRG. Our previous studies have shown that adenosine triphosphate­sensitive potassium channel (KATP) agonists can reduce postoperative pain in rats. Therefore, the changes in p120 were observed in the DRG and spinal cord of rats following the intraperitoneal injection of nicorandil, a KATP agonist. It was demonstrated that nicorandil administration could relieve mechanical pain experienced following SMIR in rats, and decrease the expression of p120 in the DRG and spinal cord. The results revealed that p120 may contribute to the prophylactic analgesic effect of nicorandil, thus providing a novel insight into the mechanism of CPSP prevention.

Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cells.

OBJECTIVES: Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases (ADs). Unlike the traditional immunosuppressants, which inadvertently impair patients' antimicrobial immunity, MSCs reduce the incidence and duration of respiratory infection. However, the underlying mechanisms are unknown. METHODS: To investigate how MSCs regulate the lung immunity and improve the defence against respiratory infection, we infected MSC-treated wild-type and lupus-prone mice with Haemophilus influenzae intranasally and determined the clearance of bacteria. Tissue damage and inflammatory cytokines were measured by H&E staining and ELISA separately. Immune cell subsets in the tissues were analysed by flow cytometry. RESULTS: MSC pretreatment prevented overwhelming inflammation and accelerated bacterial clearance in both wild-type and lupus-prone mice. Tregs increased dramatically in the lung after MSC treatment. Adoptive transfer of Tregs isolated from MSC-treated mice offered similar protection, while deletion of Tregs abrogated the protective effects of MSCs. The majority of the intravenously injected MSCs were engulfed by lung phagocytes, which in turn produced CXCL9 and CXCL10 and recruited tremendous CXCR3+ Tregs into the lung. Compared with their CXCR3- counterparts, CXCR3+ Tregs displayed enhanced proliferation and stronger inhibitory functions. Neutralisation of CXCL9 and CXCL10 significantly downregulated the migration of CXCR3+ Tregs and eliminated the benefits of MSC pretreatment. CONCLUSION: Here, we showed that by recruiting CXCR3+ Tregs, MSC treatment restricted the overactivation of inflammatory responses and prevented severe symptoms caused by infection. By discovering this novel property of MSCs, our study sheds light on optimising long-term immunosuppressive regimen for autoimmune diseases and other immune disorders.

Clinical significance of non-thyroidal illness syndrome on disease activity and dyslipidemia in patients with SLE.

OBJECTIVES: Nonthyroidal illness syndrome (NTIS), also known as low triiodothyronine (T3) syndrome, frequently affects patients with systemic lupus erythematosus (SLE) and may affect lipid metabolism. Dyslipidemia is highly prevalent and associated with the long-term prognosis of SLE. The aim of the present study was to explore the clinical significance of NTIS on disease activity and dyslipidemia in patients with SLE. METHODS: Clinical and laboratory data were collected retrospectively from 223 patients with SLE. The correlation between free triiodothyronine (FT3), SLE disease activity, and lipid profiles were estimated. The correlation coefficient (r) was calculated using a Pearson's regression model. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for dyslipidemia in SLE. RESULTS: Serum FT3 levels were negatively correlated with the levels of 24 h urine protein (UP), blood urea nitrogen (BUN), creatinine (Cr) and SLE disease activity index (SLEDAI) (all p < 0.001) in NTIS patients but not in euthyroid patients. ApoB/ApoA1 was significantly correlated with SLEDAI (p < 0.01) in NTIS patients and CRP (p < 0.001) and ESR (p < 0.01) in euthyroid patients. A multivariate analysis revealed that only FT3 exhibited an independent negative association with dyslipidemia (P = 0.01; OR = 0.48; 95% CI 0.27-0.85). CONCLUSION: NTIS frequently occurs in patients with SLE. Low FT3 is associated with disease activity in SLE patients complicated with NTIS. Low FT3 is an independent risk factor for dyslipidemia in patients with SLE.

Combined Chemical Modification of Bamboo Material Prepared Using Vinyl Acetate and Methyl Methacrylate: Dimensional Stability, Chemical Structure, and Dynamic Mechanical Properties.

Acetylation and in situ polymerization are two typical chemical modifications that are used to improve the dimensional stability of bamboo. In this work, the combination of chemical modification of vinyl acetate (VA) acetylation and methyl methacrylate (MMA) in situ polymerization of bamboo was employed. Performances of the treated bamboo were evaluated in terms of dimensional stability, wettability, thermal stability, chemical structure, and dynamic mechanical properties. Results show that the performances (dimensional stability, thermal stability, and wettability) of bamboo that was prepared via the combined pretreatment of VA and MMA (VA/MMA-B) were better than those of raw bamboo, VA single-treated bamboo (VA-B), and MMA single-treated bamboo (MMA-B). According to scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) analyses, VA and MMA were mainly grafted onto the surface of the cell wall or in the bamboo cell lumen. The antiswelling efficiency and contact angle of VA/MMA-B increased to maximum values of 40.71% and 107.1°, respectively. From thermogravimetric analysis (TG/DTG curves), the highest onset decomposition temperature (277 °C) was observed in VA/MMA-B. From DMA analysis, the storage modulus (E') of VA/MMA-B increased sharply from 15,057 Pa (untreated bamboo) to 17,909 Pa (single-treated bamboo), and the glass transition temperature was improved from 180 °C (raw bamboo) to 205 °C (single-treated bamboo).