Resting state functional connectome in breast cancer patients with fear of cancer recurrence.

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.

Unravelling the Superiority of Nonbenzenoid Acepleiadylene as a Building Block for Organic Semiconducting Materials.

Acepleiadylene (APD), a nonbenzenoid isomer of pyrene, exhibits a unique charge-separated character with a large molecular dipole and a small optical gap. However, APD has never been explored in optoelectronic materials to take advantage of these appealing properties. Here, we employ APD as a building block in organic semiconducting materials for the first time, and unravel the superiority of nonbenzenoid APD in electronic applications. We have synthesized an APD derivative (APD-IID) with APD as the terminal donor moieties and isoindigo (IID) as the acceptor core. Theoretical and experimental investigations reveal that APD-IID has an obvious charge-separated structure and enhanced intermolecular interactions as compared with its pyrene-based isomers. As a result, APD-IID displays significantly higher hole mobilities than those of the pyrene-based counterparts. These results imply the advantages of employing APD in semiconducting materials and great potential of nonbenzenoid polycyclic arenes for optoelectronic applications.

Study on strength characteristics and thickening characteristics of classified-fine cemented backfill in gold mine.

For some new mines, the utilization rate of tailings is not satisfactory when using unclassified tailings as backfill aggregate for cemented backfill. At the same time, with the progress of mineral processing technology, the tailings discharged by the concentrator gradually become finer. Therefore, cemented filling with fine-grained tailings as aggregate will become the development direction of filling technology in the future. In this paper, the feasibility of fine particle tailings backfill is studied by taking the particle tailings of-200 mesh as aggregate in Shaling gold mine. The calculation shows that the utilization rate of tailings is increased from 45.1% to 90.3% by using-200 mesh tailings as filling aggregate. The response surface central composite design method (RSM-CCD) was used to study the strength of backfill with alkali-activated cementitious material as binder by taking the mass concentration of backfill slurry and sand-binder ratio as input factors. The results show that the 28-day strength of the backfill with graded fine-grained tailings as filling aggregate can reach 5.41 MPa when the sand-binder ratio is 4, which can fully meet the needs of the mine for the strength of the backfill. The thickening test of-200 mesh fine particle tailings was carried out by static limit concentration test and dynamic thickening test. In the case of adding 35 g/t BASF 6920 non-ionic flocculant, the concentration of 64.74% tail mortar can reach 67.71% after 2 h of static thickening, and the concentration can reach 69.62% after 2 h of static thickening. The feeding speed of thickener should be controlled between 0.4 and 0.59 t/(m2 h). In this case, the underflow concentration of thickener is relatively high, which is 64.92-65.78%, and the solid content of overflow water is less than 164 ppm. The conventional full tailings thickening process was improved by using the design of high-efficiency deep cone thickener and vertical sand silo. The feasibility of fine-grained tailings as filling aggregate was demonstrated by combining the filling ratio test of fine-grained tailings, the data of thickening test and the improved thickening process. The research results can provide reference for other mines to use fine-grained tailings as filling aggregate to design filling system.

Multiple Stimulus Response 2D Framework Constructed by a Flexible Cyclotriphosphazene-Derived Carboxylic Acid Linker: Synthesis, Characterization, and Fluorescence Sensing to Phenolic Pollutants and Small-Molecule Drugs.

Hexachlorocyclotriphosphazene is one of the most representative phosphazene compounds which have been proved to have broad application prospects in many fields. However, it is an emerging research perspective to combine cyclotriphosphazene-derived polycarboxylic acid compounds with lanthanides for the construction of Tb-DPCP metal-organic framework (MOF) materials. Herein, a Tb-DPCP MOF, (CH3)2NH2[Tb3(HDPCP)(DMF)(H2O)3]·6DMF (1), was successfully prepared via the reaction of H12HDPCP [hexa(4-carboxyphenoxy) cyclotriphosphazene] and Tb(NO3)3·6H2O under the solvothermal condition. Through fluorescence sensing experiments, it was found that both nitrophenols and chlorophenols could cause the fluorescence quenching of compound 1. At the same time, the compound also exhibited nice trace detection ability for small-molecule drugs (moxifloxacin hydrochloride, balsalazide disodium, and colchicine); the limits of detection were all lower than 0.2 µM. These experimental results fully demonstrated the potential application value of 1 as a multifunctional fluorescent sensor.

Application of double-stent assisted coil embolization in intracranial vertebral artery dissecting aneurysms with mass effect.

BACKGROUND: Unruptured intracranial vertebral artery dissecting aneurysms (IVADAs) with mass effect have an extremely poor natural course, and treatment of these aneurysms remains a challenge for endovascular and surgical strategies. The aim of this study was to analyze the role of double-stent-assisted coil embolization in preventing rupture and bleeding of intracranial vertebral artery dissecting aneurysm with brainstem compression by reducing mass effect and preventing the recurrence of the aneurysm. METHODS: A total of 25 patients (mean age, 56.04±13.0 years) with unruptured IVADAs with mass effect received dual-stent-assisted coil embolization. The baseline characteristics, the change of aneurysm size on MR, the rate of retreatment, and the improvement rate of clinical symptoms and signs were analyzed retrospectively. RESULTS: All patients completed the surgical procedures successfully. No aneurysm bleeding or perforating artery occlusion occurred during the perioperative and follow-up periods. The initial maximum diameter of the aneurysm on MR was 17.5±3.6 mm. One year after treatment, the maximum diameter of the aneurysm on MR was 15.8±4.9 mm. The reduction rate of the maximum diameter of the aneurysm was 10.7±12.7%. The change of the maximum diameter before and after treatment of aneurysm was statistically significant (P<0.001). In terms of the improvement rate of clinical symptoms, 15 cases were completely improved (60.0%), 6 cases were partially improved (24.0%), and the total clinical improvement rate was 84%. Four cases (16.0%) showed no improvement or even had aggravation of clinical symptoms. In 5 cases (20.0%), aneurysms recurred. Among 4 cases involving posterior inferior cerebellar artery origin, 3 cases had the recurrence (75%). 5 recurred cases were treated with single-stent-assisted coil embolization. No residual aneurysm and recurrence were found on the follow-up angiography. CONCLUSIONS: The double-stent-assisted coil embolization procedure is very safe and reliable. It can effectively prevent the aneurysm from continuing to grow and rupture and thereby reduce the clinical symptoms caused by the mass effect.

Novel T-cell signature based on cell pair algorithm predicts survival and immunotherapy response for patients with bladder urothelial carcinoma.

Background: T-cell-T-cell interactions play important roles in the regulation of T-cells' cytotoxic function, further impacting the anti-tumor efficacy of immunotherapy. There is a lack of comprehensive studies of T-cell types in bladder urothelial carcinoma (BLCA) and T-cell-related signatures for predicting prognosis and monitoring immunotherapy efficacy. Methods: More than 3,400 BLCA patients were collected and used in the present study. The ssGSEA algorithm was applied to calculate the infiltration level of 19 T-cell types. A cell pair algorithm was applied to construct a T-cell-related prognostic index (TCRPI). Survival analysis was performed to measure the survival difference across TCRPI-risk groups. Spearman's correlation analysis was used for relevance assessment. The Wilcox test was used to measure the expression level difference. Results: Nineteen T-cell types were collected; 171 T-cell pairs (TCPs) were established, of which 26 were picked out by the least absolute shrinkage and selection operator (LASSO) analysis. Based on these TCPs, the TCRPI was constructed and validated to play crucial roles in survival stratification and the dynamic monitoring of immunotherapy effects. We also explored several candidate drugs targeting TCRPI. A composite TCRPI and clinical prognostic index (CTCPI) was then constructed, which achieved a more accurate estimation of BLCA's survival and was therefore a better choice for prognosis prediction in BLCA. Conclusions: All in all, we constructed and validated TCRPI based on cell pair algorithms in this study, which might put forward some new insights to increase the survival estimation and clinical response to immune therapy for individual BLCA patients and contribute to the personalized precision immunotherapy strategy of BLCA.

The uPA System Differentially Alters Fibroblast Fate and Profibrotic Ability in Skin Fibrosis.

Skin fibrosis is a common pathological feature of various diseases, and few treatment strategies are available because of the molecular pathogenesis is poorly understood. The urokinase-type plasminogen activator (uPA) system is the major serine protease system, and its components uPA, urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1(PAI-1) are widely upregulated in fibrotic diseases, including hypertrophic scars, keloids, and scleroderma. Here, we found that the successful binding of uPA and uPAR activates the downstream peroxisome proliferator-activated receptor (PPAR) signalling pathway to reduce the proliferation, migration, and contraction of disease-derived fibroblasts, contributing to the alleviation of skin fibrosis. However, increased or robust upregulation of the inhibitor PAI-1 inhibits these effects, suggesting of the involvement of PAI-1 in skin fibrosis. Subsequent in vivo studies showed that uPAR inhibitors increased skin fibrosis in mouse models, while uPA agonists and PAI-1 inhibitors reversed these effects. Our findings demonstrate a novel role for the uPA system and highlights its relationships with skin fibrosis, thereby suggesting new therapeutic approaches targeting the uPA system.

A method for void fraction measurement of bubble/slug flow in small channels based on contactless impedance detection.

The flow parameter measurement of the gas-liquid two-phase flow in small channels is very crucial and challenging in both academia and industry. Conventional techniques based on radiations, optics, acoustics, or electrics most lose their superiorities in the scenario with small channels due to the spatial limitation and the online and contactless measurement requirements. In addition, the conductive characteristic of the two-phase flow is equivalent to an impedance rather than a resistance due to the existence of multi-phases. The equivalent impedance information of the two-phase flow, especially the imaginary part, is promising to provide more flowing details but has seldom been detected or analyzed. In this paper, a method for the void fraction measurement of bubble/slug flow in small channels is proposed. The method implements void fraction measurement in a contactless way, based on the acquisition of the total impedance information of the gas-liquid two-phase flow. First, a new contactless impedance detection sensor is designed, based on the simulated inductor technique and the analog phase sensitive demodulation technique, to obtain the complete equivalent impedance information of the two-phase fluid. Then, based on the flow pattern identification result, the void fraction measurement model is developed, which is a fusion of the relationships between the void fraction and the real part/the imaginary part of the equivalent impedance information, respectively. Experimental results on prototypes with different inner diameters (2.48, 3.64, and 4.52 mm, respectively) validate the effectiveness of the proposed void fraction method. The maximum void fraction measurement biases are within 5.0%.

Fibroblasts: Heterogeneous Cells With Potential in Regenerative Therapy for Scarless Wound Healing.

In recent years, research on wound healing has become increasingly in-depth, but therapeutic effects are still not satisfactory. Occasionally, pathological tissue repair occurs. Influencing factors have been proposed, but finding the turning point between normal and pathological tissue repair is difficult. Therefore, we focused our attention on the most basic level of tissue repair: fibroblasts. Fibroblasts were once considered terminally differentiated cells that represent a single cell type, and their heterogeneity was not studied until recently. We believe that subpopulations of fibroblasts play different roles in tissue repair, resulting in different repair results, such as the formation of normal scars in physiological tissue repair and fibrosis or ulcers in pathological tissue repair. It is also proposed that scarless healing can be achieved by regulating fibroblast subpopulations.

Paeoniflorin-6'-o-benzene sulfonate (CP-25) improves vasculitis through inhibiting IL-17A/JAK/STAT3 signaling pathway in endothelial cells of HFD CIA rats.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.

New method for bubble/slug velocity measurement in small channels.

Based on the C4D technique and cross correlation velocity measurement technique, a new method for bubble/slug velocity measurement of the gas-liquid two-phase flow in small channels is proposed. A new C4D sensor, which is suitable for the parameter measurement of the gas-liquid two-phase flow in small channels, is developed by introducing the principle of capacitive reactance elimination. With two new C4D sensors, a bubble/slug velocity measurement system is developed, and the bubble/slug velocity is determined by the cross correlation velocity measurement technique. To verify the effectiveness of the proposed bubble/slug velocity measurement method, three prototypes of bubble/slug velocity measurement systems with different diameters (1.82 mm, 2.65 mm, and 2.96 mm, respectively) were established, and the bubble/slug measurement experiments were carried out. The research results show that the capacitive reactance elimination is an effective way to overcome the unfavorable influence of the coupled capacitances on measurement results. The experimental results indicate that the proposed method can successfully realize the bubble/slug velocity measurement in small channels, and the velocity measurement accuracy is satisfactory. For the three prototypes of the bubble/slug velocity measurement system, the maximum relative errors of the bubble/slug velocity measurement are all less than 5%.

Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pathway in Rheumatoid Arthritis.

OBJECTIVE: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. METHODS: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB. RESULTS: The percentage of CD19-CD27+CD138+ plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19+ total B cells, CD19+CD27+ memory B cells and CD19-CD27+CD138+ plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells. CONCLUSION: B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.

IgD-Fc-Ig fusion protein, a new biological agent, inhibits T cell function in CIA rats by inhibiting IgD-IgDR-Lck-NF-κB signaling pathways.

IgD-Fc-Ig fusion protein, a new biological agent, is constructed by linking a segment of human IgD-Fc with a segment of human IgG1-Fc, which specifically blocks the IgD-IgDR pathway and selectively inhibits the abnormal proliferation, activation, and differentiation of T cells. In this study we investigated whether IgD-Fc-Ig exerted therapeutic effects in collagen-induced arthritis (CIA) rats. CIA rats were treated with IgD-Fc-Ig (1, 3, and 9 mg/kg) or injected with biological agents etanercept (3 mg/kg) once every 3 days for 40 days. In the PBMCs and spleen lymphocytes of CIA rats, both T and B cells exhibited abnormal proliferation; the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1(CD4+IFN-γ+), and Th17(CD4+IL-17+) were significantly increased, whereas the Treg (CD4+CD25+Foxp3+) cell percentage was decreased. IgD-Fc-Ig administration dose-dependently decreased the indicators of arthritis; alleviated the histopathology of spleen and joint; reduced serum inflammatory cytokines levels; decreased the percentages of CD3+ total T cells, CD3+CD4+ Th cells, CD3+CD4+CD25+-activated Th cells, Th1 (CD4+IFN-γ+), and Th17(CD4+IL-17+); increased Treg (CD4+CD25+Foxp3+) cell percentage; and down-regulated the expression of key molecules in IgD-IgDR-Lck-NF-κB signaling (p-Lck, p-ZAP70, p-P38, p-NF-κB65). Treatment of normal T cells with IgD (9 µg/mL) in vitro promoted their proliferation. Co-treatment with IgD-Fc-Ig (0.1-10 µg/mL) dose-dependently decreased IgD-stimulated T cell subsets percentages and down-regulated the IgD-IgDR-Lck-NF-κB signaling. In summary, this study demonstrates that IgD-Fc-Ig alleviates CIA and regulates the functions of T cells through inhibiting IgD-IgDR-Lck-NF-κB signaling.

Submucosal tunneling endoscopic resection for an unusually sized esophageal submucosal tumor protruding into the mediastinum

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Submucosal tunneling endoscopic resection for an unusually sized esophageal submucosal tumor protruding into the mediastinum.

A 50-year-old female came to our hospital with a 6-month history of upper abdominal discomfort. An upper endoscopy detected a protruding lesion that measured 3.0×2.0 cm at around 35-38 cm from the incisors located on the posterior wall. Endoscopic ultrasonography revealed a homogeneous hyperechoic mass located in the muscularis propria, with no malignant features. Contrast-enhanced CT was also performed. A submucosal tunneling endoscopic resection (STER) was performed. A longitudinal mucosal incision was made and a submucosal tunnel created, which uncovered an irregularly giant tumor. The size of the resected tumor was 3.0×4.0×1.5cm and the histopathological analysis identified leiomyomas. The patient was discharged 7 days after the procedure and 3 months after the surgery there was no recurrence on the CT scan. Meanwhile, the discomfort of the patient was relieved after STER and there were no severe complications during the 6-month follow-up. DISCUSSION Esophageal leiomyoma is a benign submucosal tumor derived from the muscularis propria layer of the esophagus [1]. STER has been demonstrated to be safe and effective for treating small (≤3.5 cm) and solitary esophageal leiomyoma with low complication rates [2-3]. Most esophageal leiomyoma grow into the lumen and their positions in the tunnel are relatively superficial and the entire surgery is comparatively safe. In this case, the tumor was very large and was close to the mediastinum, which greatly increases the difficulty of surgery. However, STER is recommended according to our experience, even in rare cases.

On the Design of a New Simulated Inductor Using a Contactless Electrical Tomography System as an Example.

This work reports a new simulated inductor which is suitable for a Contactless Electrical Tomography (CET) system and can effectively overcome the unfavorable influence of coupling capacitance on the measurement results. By detailed analysis and comparison, it is found that the grounded simulated inductor has a simple circuit construction but its output current is not equal to its input current, while the floating simulated inductor can be used as an independent inductor module but its circuit structure is relatively complex. A new simulated inductor is designed by compensating the currents from the common node of an introduced independent power source to the main circuit. The new simulated inductor combines the advantages of the grounded simulated inductor and the floating simulated inductor. It has the simple construction similar to that of the grounded simulated inductor and its input current is equal to the output current, which means it can be used as an independent module. The impedance measurement and practical image reconstruction experiments were carried out to verify the effectiveness of the new simulated inductor. The experimental results show that the design of the new simulated inductor is successful, and the performance of the impedance measurement is satisfactory. The signal-to-noise ratio of the CET system is improved. Meanwhile, the research work also indicates that in the case when the independent power source is not available, the new simulated inductor is also an effective alternative method. But the phase difference between input signal and output signal is approximately 90° when the elimination principle is realized.

Paeoniflorin-6'-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents.

Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a new ester derivative of paeoniflorin with improved lipid solubility and oral bioavailability, as well as better anti-inflammatory activity than its parent compound. In this study we explored whether CP-25 exerted therapeutic effects in collagen-induced arthritis (CIA) mice through regulating B-cell activating factor (BAFF)-BAFF receptors-mediated signaling pathways. CIA mice were given CP-25 or injected with biological agents rituximab or etanercept for 40 days. In CIA mice, we found that T cells and B cells exhibited abnormal proliferation; the percentages of CD19+ total B cells, CD19+CD27+-activated B cells, CD19+BAFFR+ and CD19+TACI+ cells were significantly increased in PBMCs and spleen lymphocytes. CP-25 suppressed the indicators of arthritis, alleviated histopathology, accompanied by reduced BAFF and BAFF receptors expressions, inhibited serum immunoglobulin levels, decreased the B-cell subsets percentages, and prevented the expressions of key molecules in NF-κB signaling. Furthermore, we showed that treatment with CP-25 reduced CD19+TRAF2+ cell expressions stimulated by BAFF and decreased TRAF2 overexpression in HEK293 cells in vitro. Thus, CP-25 restored the abnormal T cells proliferation and B-cell percentages to the normal levels, and normalized the elevated levels of IgA, IgG2a and key proteins in NF-κB signaling. In comparison, rituximab and etanercept displayed stronger anti-inflammatory activities than CP-25; they suppressed the elevated inflammatory indexes to below the normal levels in CIA mice. In summary, our results provide evidence that CP-25 alleviates CIA and regulates the functions of B cells through BAFF-TRAF2-NF-κB signaling. CP-25 would be a soft immunomodulatory drug with anti-inflammatory effect.

Neurocutaneous Melanosis in an Adult Patient with Intracranial Primary Malignant Melanoma: Case Report and Review of the Literature.

BACKGROUND: To explore the clinical characteristics of neurocutaneous melanosis (NCM) in adult patients to help improve diagnosis and treatment of this disease, we present a rare case of an adult patient suffering from NCM with malignant melanoma, as well as a review of the relevant Chinese and English literature. CASE DESCRIPTION: The patient reported here plus the patients identified in our literature review total 30 adults with NCM (20 males [66.7%] and 10 females [33.3%]), age 19-65 years (average, 27.9 years). These include 24 cases of malignant melanoma (80.0%), 3 cases of melanocytoma (10.0%), 2 cases of diffuse melanocytosis (6.7%), and 1 case of unknown pathology (3.3%). Satellite nevi were reported in 25 cases (83.3%) and in 5 cases their presence was unknown (16.7%). Intracranial lesions were present in 28 cases (93.3%), and intraspinal lesions were present in 2 cases (6.7%). There are 4 cases of combined hydrocephalus (13.3%), and 2 cases of combined Dandy-Walker deformity (6.7%). CONCLUSIONS: NCM is a rare disease, especially in adults. With the onset of symptoms, the diagnosis is generally confirmed. In children with congenital giant nevus, regular periodic surveys of the central nervous system (brain and spinal cord) with magnetic resonance imaging or cerebrospinal fluid analysis should be performed to diagnose NCM. Active treatment should be undertaken to improve the prognosis.

Development of a SYBR green-based real-time quantitative PCR assay to detect PCV3 in pigs.

Porcine circovirus 3 (PCV3) has been reported in cases of porcine dermatitis and nephropathy syndrome, reproductive failure, cardiac and multi-systemic inflammation. A SYBR green-based real-time quantitative PCR (qPCR) assay was established in this study to detect PCV3 in 203 clinical samples from suckling piglets affected by congenital tremors in China. The limit of detection (LOD) of PCV3 was 1.73×104 copies/µL for gel electrophoresis and 1.73×102 copies/µL for SYBR green-based real-time qPCR. The melt curve analysis showed a single melt peak at 82.5°C.The intra-assay coefficient of variation was up to 1.83% and the inter-assay coefficient of variation was up to 2.27%. The PCV3 positive detection rate of 203 clinical samples for the SYBR green-based real-time qPCR and the conventional PCR was 86.70% (176/203) and 26.60% (54/203), respectively. Each tissue detected in the SYBR green-based real-time qPCR showed a higher positive rate than that detected in the conventional PCR. These results indicated that the SYBR green-based real-time qPCR assay is a powerful method with high sensitivity, specificity and reproducibility for epidemiological investigations of PCV3.

CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents.

Paeoniflorin-6'-O-benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.