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Macrophage activation syndrome (MAS) is a major cause of morbidity and mortality in pediatric rheumatology. We aimed to further understand the clinical features, treatment, and outcome of MAS in China. A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018. Eighty patients with MAS were enrolled, including 53 cases with systemic juvenile idiopathic arthritis (SJIA-MAS), 10 cases of Kawasaki disease (KD-MAS), and 17 cases of connective tissue disease (CTD-MAS). The clinical and laboratory data were collected before (pre-), at onset, and during full-blown stages of MAS. We compared the data among the SJIA-MAS, KD-MAS, and CTD-MAS subjects. 51.2% of patients developed MAS when the underlying disease was first diagnosed. In patients with SJIA, 22.6% (12/53) were found to have hypotension before the onset of SJIA-MAS. These patients were also found to have significantly increased aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as decreased albumin (P

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood driven by aberrant pathways of T-cell activation. T helper 17 (Th17)/regulatory T cell (Treg) imbalance plays critical roles in the pathogenesis of arthritis. MicroRNA-125b (miR-125b) was upregulated after the activation of the initial CD4+ T cells, and could regulate the differentiation of CD4+ T cells. However, the effects of miR-125b on Th17/Treg imbalance and differentiation of Th17/Treg cells remain unknown. In this study, we evaluated the expression of miR-125b in the peripheral blood mononuclear cells (PBMCs) of children with JIA, and the relationship of miR-125b with Th17/Treg imbalance. Then, we used lentivirus vector-mediated overexpression technology to investigate the regulatory function of miR-125b in CD4+ T cells or dendritic cell/CD4+ T co-culture system. Decreased miR-125b expression in PBMCs and CD4+ T cells of JIA patients was negatively correlated with the ratio of Th17/Treg cells. It also correlated negatively with retinoic acid receptor-related orphan receptor γt but positively with Forkhead box protein 3 at transcriptional levels. Furthermore, we found that miR-125b overexpression inhibited Th17 cell differentiation, whereas facilitated the differentiation of Treg cells. MiR-125b upregulation led to the decrease of Th17-secreting cytokines but the increase of the Treg-secreting cytokines. Our results demonstrate that miR-125b participated in regulating Th17/Treg cell differentiation and imbalance in JIA patients. These findings provide novel insight into the critical role of miR-125b in the Th17/Treg imbalance of JIA, and raise the distinct possibility that miR-125b may prove to be a potential therapeutic target for JIA.

Volatile anesthetics have been proven to treat experimental sepsis. Sevoflurane combined with oxygen is widely applied in the clinic, and our previous study indicated that this regimen significantly reduced sepsis-induced inflammatory responses and that inhibition of NF-κB pathway activation may contribute to this protection effect. Furthermore, our previous data has shown that sevoflurane combined with oxygen has prevention effect on sepsis-induced lung injury properties and bactericidal properties, but the mechanism is not well understood. Nitric oxide (NO) has been shown to have bactericidal effects and mitigating effects on lung injury, but this is not well studied in sepsis. The present study suggested that in cecal ligation and puncture (CLP)-induced sepsis, sevoflurane combined with oxygen had bactericidal effects and reduced neutrophil infiltration into the lung, preventing inflammatory lung injury. NO production was significantly induced in peritoneal lavage fluid and bronchoalveolar lavage fluid. These effects were abolished by pharmacological inhibition of nitric oxide synthase activity. Thus, our findings suggest that sevoflurane combined with oxygen exerts bactericidal effects and prevents lung injury in sepsis through the NO pathway.

Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated. Whether these mechanisms are beneficial or detrimental remains a matter of controversy, but there is no doubt as to their vital functions. An understanding of the mechanisms of injury and recovery after ICH is crucial to develop therapeutic strategies. In this review, we summarize the related studies and highlight the roles of autophagy, ER stress, and the UPR in disease, especially in ICH. We also provide an overview of therapeutic approaches that target autophagy, and we discuss the prospects for modulating autophagy, ER stress, and UPR mechanisms in ICH therapy.

Background: Intracerebral hemorrhage (ICH) is a life-threatening disease that confuses us for centuries. Acupuncture as a kind of Chinese traditional treatment has been empirically established and widely used in clinics in China, especially for stroke victims. Studies proved that GV20 penetrating GB7, a kind of needling manipulation, with which a needle is inserted into GV20 and then to GB7 under the scalp, is especially effective on the treatment of this disease. Wingless-type1 (Wnt1) is a key factor of Wnt/β-catenin signal pathway, which could promote regeneration and remodeling of neural function after ICH by affecting proliferation and differentiation of the neural stem cells (NSCs). The study on the expression of Wnt1 induced by GV20 penetrating GB7 may give out the theoretical principle of the treatment.Objective: The goal of this work is to observe the effect of GV20 penetrating GB7 needling on the protein/ mRNA expression of Wnt1 in brain tissue of ICH rats.Methods: In this experiment, we focused on observing the protein/mRNA expression level of Wnt1 by Western blot and real-time fluorescent quantitative PCR (RTFQ PCR) in the rats with ICH, which were treated by Dickkopfrelated protein 1 (DKK1), acupuncture or no intervention, comparing with the healthy rats without any treatment at fixed time points.Results: This study revealed that the expression of Wnt1 had the similar trend in all groups at each time point of corresponding treatment, which began to increase from the third day (3d), reached the peak on the seventh day (7d) then decreased gradually. The acupuncture treatment group showed a higher level of expression.Conclusion: The results show that GV20 penetrating GB7 has advantage on promoting the protein/mRNA expression of Wnt1, activates the intracellular Wnt pathway, and regulates the transcription of downstream target genes, affecting proliferation and differentiation of the neural stem cells (NSCs), thereby initiates endogenous repair mechanisms of the organism itself. This study provides a powerful scientific basis for acupuncture treatment on ICH.

Aim of the study Results of recent published studies on the association between the COX-2 8473T>C polymorphism and the risk of breast cancer have often been conflicting. To make a more precise estimation of the potential relationship, a meta-analysis was performed. Material and methods A total of seven case-control studies with 7,033 cases and 9,350 controls were included in the current meta-analysis through searching the databases of PubMed, Embase, and Cochrane Library (up to March 1st, 2013). The odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the strength of the association. The meta-analysis was conducted in a fixed/random effect model. Results We found no significant associations for all genetic models after all studies were pooled into the meta-analysis (for C vs. T: OR = 0.974, 95% CI: 0.906–1.047, p = 0.471; for CC vs. TT: OR = 0.957, 95% CI: 0.803–1.140, p = 0.62; for TC vs. TT: OR = 0.964, 95% CI: 0.881–1.055, p = 0.421; for CC + TC vs. TT: OR = 0.963, 95% CI: 0.880–1.053, p = 0.406; for CC vs. TT + TC: OR = 0.978, 95% CI: 0.831–1.15, p = 0.788). We also observed no obvious associations in the subgroup analyses by ethnicity (Caucasian) and source of controls (population based, PB) for all genetic models. Conclusions Current evidence suggests that the COX-2 8473T>C polymorphism is not associated with breast cancer risk.

Inflammation plays an important role in nerve defects caused by intracerebral hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type lectin/spleen tyrosine kinase (Mincle/Syk) signaling pathway is a potential new target for treating cerebral hemorrhage. In this study, we aimed to determine whether acupuncture through Baihui (DU20) to Qubin (GB7) is an effective treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway. An intracerebral hemorrhage rat model was established by autologous blood infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was performed for 30 minutes, once every 12 hours, for a total of three times. Piceatannol (34.62 mg/kg), a Syk inhibitor, was intraperitoneally injected as a control. Modified neurological severity score was used to assess neurological function. Brain water content was measured. Immunohistochemistry and western blot assay were used to detect immunoreactivity and protein expression levels of Mincle, Syk, and CARD9. Real-time polymerase chain reaction was used to determine interleukin-1β mRNA levels. Hematoxylin-eosin staining was performed to observe histopathological changes. Our results showed that acupuncture through Baihui to Qubin remarkably improved neurological function and brain water content, and inhibited immunoreactivity and expression of Mincle, Syk, CARD9, and interkeukin-1β. Moreover, this effect was similar to piceatannol. These findings suggest that acupuncture through Baihui to Qubin can improve neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk signaling pathway.

Juvenile idiopathic arthritis (JIA) is a common autoimmune disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The protein tyrosine phosphatase nonreceptor 22 (PTPN22) and signal transducer and activator of transcription factor 4 (STAT4) have been recognized as susceptibility genes for numerous autoimmune diseases. Associations of STAT4 rs7574865 G/T and PTPN22 (rs2488457 G/C and rs2476601 C/T) polymorphisms with JIA have repeatedly been replicated in several Caucasian populations. The aim of this study was to investigate the influence of three polymorphisms mentioned above on the risk of developing JIA in Han Chinese patients. Genotyping was performed on a total of 137 Chinese patients with JIA (JIA group) and 150 sex and age frequency-matched healthy volunteers (Control group). The single-nucleotide polymorphisms (SNP) were determined by using direct sequencing of PCR-amplified products. There were significant differences of PTPN22 rs2488457 G/C and STAT4 rs7574865 G/T polymorphisms between both groups. However, no significant difference was observed in distribution frequencies of PTPN22 rs2476601 polymorphism. The association with the PTPN22 rs2488457 G/C polymorphism remained significant in the stratifications by age at onset, ANA status, splenomegaly, lymphadenectasis and involvement joints. As with the STAT4 rs7574865 G/T polymorphisms, the enthesitis-related arthritis and presence of hepatomegaly had strong effect on the association. Our data strengthen STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms as susceptibility factors for JIA.

This study aims to investigate the prognostic factors and long-term treatment outcome in patients with early stage nasal natural killer (NK)/T-cell lymphoma. Sixty-four patients were recruited in this study, whose clinical and laboratory data were collected from hospital records. Early stage (stage IE: 51, stage IIE: 13) nasal NK/T-cell lymphoma (NNTCL) was established according to Ann Arbor staging classification. Among these patients, 23 received radiotherapy (RT) alone, the remaining 41 cases were treated with radiochemotherapy (RCT) comprised of 1-6 cycles of anthracycline-based chemotherapeutic regimens. Results show that the median overall survival (OS) time was 41 months. The 5-year OS and progression-free survival rates were 59.2 and 52.3%, respectively. The 5-year OS rate for patients who received RT alone was 57.9%, whereas that for patients who received RCT was 61.5% (P = 0.47). There is no significant difference between two treatment modalities. Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (PS) score > or = 2, local tumor invasion out of nasal cavity, and lower complete remission (CR) rates in the initial treatment were significant unfavorable independent prognostic factors. Taken together, our study suggests that RCT did not improve the survival rate of patients with early stage NNTCL. PS score before treatment, local tumor invasion out of nasal cavity, and CR rate of the primary treatment may be independent prognostic factors among the subtype lymphoma entity.