Both CV and VVC can be identified based on the quantity of lactobacilli, the morphology of the epithelial cells, and the absence or presence of Candida species and other pathogens, and the misdiagnosis of CV as VVC can be avoided.

Regulatory CD19 + CD24 hi CD27 + B cells were proved to be numerically decreased and functionally impaired in the peripheral blood (PB) from rheumatoid arthritis (RA), with the potential of converting into osteoclast-priming cells. However, the distribution and function of CD19 + CD24 hi CD27 + B cells in RA synovial fluid (SF) were unclear. In this study, we investigated whether RA SF CD19 + CD24 hi CD27 + B cells were increased and associated with bone destruction. We found that the proportion of RA SF CD19 + CD24 hi CD27 + B cells was increased significantly, and was positively correlated with swollen joint counts, tender joint counts and disease activity. CXCL12, CXCL13, CCL19 contributed to the recruitment of CD19 + CD24 hi CD27 + B cells in RA SF. Notably, CD19 + CD24 hi CD27 + B cells in the Sf from RA expressed significantly more RANKL compared to OA and that in the PB from RA. Critically, RA CD19 + CD24 hi CD27 + B cells promoted osteoclast (OC) differentiation in vitro, and the number of OCs was higher in cultures with RA SF CD19 + CD24 hi CD27 + B cells than in those derived from RA PB. Collectively, these findings revealed the accumulation of CD19 + CD24 hi CD27 + B cells in SF and their likely contribution to joint destruction in RA. Modulating the status of CD19 + CD24 hi CD27 + B cells might provide novel therapeutic strategies for RA. Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by synovitis in multiple joints and progressive bone destruction 1. Mounting evidence indicates that the imbalance between bone loss and bone formation attributes to bone damage in RA 2. Bone-resorbing osteoclasts (OCs) are the cells responsible for bone erosion in RA patients 3. Receptor activator of NF-κB ligand (RANKL) and its receptor, RANK, are key positive extracellular regulators of osteoclast formation and activation 4,5. Early studies of RANKL production in RA indicated that synovial fibroblasts and activated T cells produce excess RANKL and may contribute to osteoclastic bone resorption 6-8. However, recent increasing researches have demonstrated that B cells play an important role in facilitating bone erosion in RA by both promoting OC differentiation and by suppressing osteoblast (OB) development 9-13. Scientists found that synovial B cells are a major source of RANKL and Fc-receptor like 4 (FcRL4) positive B cells are defined a pro-inflammatory, RANKLproducing B cells in RA 9,10. Thereafter, switched-memory B cells have been reported in RA peripheral blood and synovial tissue, where they are thought to express high level of RANKL and promoted osteoclastogenesis 11,12. Moreover, B cells have been proved to inhibit bone formation in RA by secreting multiple OB inhibitors 13 , furtherly indicating the tight relationship between B lymphocytes and bone homeostasis. As reported, CD19 + CD24 hi CD27 + B cells were identified as IL-10 producing B cell subsets in human, which also termed as regulatory B10 cells 14. Several studies have shown that these B10 cells were numerically decrea...

Anaphylaxis is a serious reaction that may cause death in half an hour without diagnostic characteristic in autopsies. Mast cell (MC) degranulation combined with immunoglobulin E (IgE) plays the key roles in anaphylaxis. Unavailability of serum and instability of measured serum in postmortem diagnoses sometimes limit the opinion of medical experts. Allergic tissues are more accessible than serum, and there is a little research on degranulated mast cells and IgE in different human tissues, whereas we hardly know whether the expression will keep stable over the increasing postmortem interval (PMI). In this research, we examined the mast cell counts and degranulation rates and gE contents in human throat, lung, and intestine tissues and preliminarily investigated the correlation of these markers with PMI in anaphylaxis-associated death. Allergic samples showed a significant increase in mast cell degranulation accompanied by an increase in IgE levels than the control group, but the expression was not significantly correlated with increasing PMI only in throat tissues. Elevated mast cell degranulation combined with increased IgE levels may be a reliable biomarker for forensic diagnosis of human tissues due to IgE-mediated allergic sudden death.

Objective Inter‐alpha‐trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA. Methods After the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme‐linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐17A at baseline of RA patients were also detected by ELISA. Results ITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2–213.5) ng/mL) than in HCs (306.8 (IQR: 238.9–435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C‐reactive protein (CRP) (rs = −0.358, p < 0.001) and 28‐joint disease activity score using erythrocyte sedimentation rate (DAS28‐ESR) (rs = −0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF‐α (rs = −0.337, p = 0.001), IL‐6 (rs = −0.221, p = 0.033), and IL‐17A (rs = −0.368, p < 0.001) in RA patients, but not correlated with IL‐1β (rs = −0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05). Conclusion Circulating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.

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Background: Postpartum depression (PPD) is a frequent mental disorder during the first year after delivery. Previous studies reported that patients with labor analgesia revealed lower incidence of PPD compared to those without. However, most pregnant women gave birth by labor analgesia or cesarean section in China, it is still unclear that whether there is a difference of the effects of labor analgesia and cesarean section on PPD.Methods: A single-centered, prospective cohort clinical study was designed. One hundred ninety-eight patients with single pregnancy at full term were allocated to receive epidural labor analgesia (group LA) or cesarean section with epidural anesthesia (group CS) according to the maternal preference of delivery and professional suggetions of obstetricians and anesthesiologists. PPD was assessed with Edinburgh Postnatal Depression Scale (EPDS) scores ≥10 at 6 weeks postpartum. Maternal and neonatal variables in the perinatal period were recorded. Multivariate logistical regression analysis was conducted to evaluate the associated factors of PPD. Results: 11 patients in group LA and 26 patients in group CS was diagnosed as PPD. The incidence of PPD in group LA was lower than group CS (P=0.011). Eight potential predictor factors (labor analgesia, family income, duration of labor, antenatal depression, perinatal classes attending, neonate of male, EPDS scores at 3 days postpartum and adverse event at 6 weeks postpartum) were correlated with PPD. And it was reported in the final model that labor analgesia was the protective factor of PPD, however, high family income and EPDS scores at 3 days postpartum were associated with an increased risk of PPD. Conclusions: Patients with epidural labor analgesia were associated with lower incidence of PPD compare to those with cesarean section with epidural anesthesia. Epidural labor analgesia, family income and EPDS scores in the early postpartum period were the independent predictors of PPD. Trial registration: This clinical trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx). Number: ChiCTR1900020510. Registered on: 3/1/2019.

15 Plasma factor VIII (fVIII) circulates in complex with von Willebrand factor (VWF) and is rapidly cleared in the absence of VWF. Previous in vitro studies have 1) localized the fVIII-binding region of VWF to the N-terminus, comprised of the contiguous D' and D3 domains and 2) observed reduced affinity for fVIII upon alterations to the tertiary structure of VWF. To gain insight into the structure-function of VWF for fVIII stabilization, we tested VWF fragments for in vivo fVIII stabilization and investigated the architecture of a VWF fragment in complex with fVIII. For the in vivo study, fragments of murine Vwf cDNA were cloned into the hepatic-specific expression vector, pLIVE, and modified to fuse tandem E and FLAG tags to the C-terminus. The following VWF fragments were expressed in vivo by hydrodynamic tail vein injection into Vwf−/− mice: 1) a monomer of the VWF D'D3 domains (monoD'D3; M1-C22, S764-P1274); 2) a truncation of monomeric D'D3 (truncD'D3; M1-C22, S764-R1035); 3) dimers of D'D3 (diD'D3; M1-P1274); 4) multimers of D'D3 (multiD'D3; M1-P1274, G2713-K2813); 5) dimers of mature VWF subunits (DPro, M1-C22, S764-K2813); or 6) full length, multimeric VWF (wtVWF, M1-K2813). Expression of all VWF fragments persisted throughout the period of observation (4 weeks) with peak antigenic levels at 1 or 3 days post-injection. Prolonged elevation of plasma fVIII activity (fVIIIa) from ∼10% to ∼50–200% were observed (100% defined as the fVIIIa level of pooled platelet poor plasma from 10 wild type C57BL/6 mice) for all but the truncated monomer of D'D3 (Figure 1). Significantly increased fVIIIa levels (p<0.05, relative to pre-injection) were first observed at 1 day, peaked at 3 days, and persisted for the duration of observation. A minimal VWF fragment (S764-R1035, truncD'D3) reported to bind fVIII in vitro significantly increased plasma fVIIIa to 34% only at 3 days post-injection. Clearance of VWF fragments from circulation were determined from injections of pooled platelet poor plasma containing recombinant VWF fragments derived from hydrodynamically injected mice into naïve Vwf−/− mice. Nonlinear regression estimated the half-life for monoD'D3 (3.4hr), diD'D3 (2.1hr), multiD'D3 (2.3hr), DPro (2.8hr), and wtVWF (3.5hr). To examine how dimers of D'D3 bind fVIII, diD'D3 from HepG2 conditioned media was purified either alone or with recombinant fVIII, and negative stained samples were visualized by electron microscopy (EM). Single-particle EM analysis revealed that each subunit of the dimer binds 1 fVIII molecule. 3D EM reconstructions indicate that the light chain of fVIII directly interacts with, and potentially induces torsion in the flexible D'D3 domains of VWF. Together, these results emphasize the importance of VWF's tertiary structure in fVIII stabilization and that the N-terminal D'D3 alone is sufficient to support fVIII survival in vivo. These findings could lead to improved methods of recombinant fVIII production and the development of novel approaches to treatment for hemophilia and von Willebrand disease. Figure 1. fVIIIa of hydrodynamically injected mice at indicated time points. Figure 1. fVIIIa of hydrodynamically injected mice at indicated time points. Disclosures: Ginsburg: Shire Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Portola Pharmaceuticals: Consultancy; Catalyst Biosciences: Consultancy; Baxter Pharmaceuticals: benefit from payments to Children's Hosptial, Boston, and the University of Michigan Patents & Royalties; Merck Pharmaceuticals: Consultancy.

Molar pregnancies are associated with extremely high levels of BhCG, out of proportion to the stage of pregnancy. However, urine and serum BhCG assays can paradoxically be negative, despite the high BhCG levels, leading to misdiagnosis and delayed treatment. This is due to saturation of the assay by the BhCG molecules. We present such a case where the initial urine pregnancy test was negative in an advanced complete molar pregnancy. Primary care and emergency department physicians should be mindful of this possibility and go on to do serum BhCG with sample dilution in cases where pregnancy is strongly suspected.