[Analysis of the clinical characteristics of 25 cases with parenchymal neuro-Behcet's disease].

Objective: To retrospectively investigate the clinical data, radiological characteristics, treatment, and outcome of patients with parenchymal neuro-Behcet's disease (P-NBD) with particular emphasis on dizziness. Methods: This was a cross-sectional study of clinical data from 25 patients with a confirmed diagnosis of P-NBD who were admitted to the Department of Neurology of the First Medical Center of Chinese People's Liberation Army General Hospital between 2010 and 2022. The median age of the population was 37 years (range: 17-85 years). Clinical data were retrospectively analyzed, including gender, age of onset, disease duration, clinical manifestations, serum immune indicators, cerebrospinal fluid (CSF) routine biochemical and cytokine levels, cranial and spinal magnetic resonance imaging (MRI) findings, treatment, and outcome. Results: The majority of patients were male (16 cases; 64.0%), the mean age of onset was (28±14) (range: 4-58 years), and the disease course was acute or subacute. Fever was the most common clinical presentation, and the complaint of dizziness was not uncommon (8/25 patients). Analysis of serum immune indices, including complement (C3 and C4), erythrocyte sedimentation rate, interleukin-1 (IL-1), IL-6, IL-8 and tumor necrotic factor-alpha were abnormal in 80.0% of patients (20/25). Most of the 16/25 patients who underwent lumbar puncture tests had normal intracranial pressure and increased CSF white cell count and protein [median values were 44 (15-380) ×106/L and 0.73 (0.49-2.81) g/L, respectively]. Of the five patients who underwent CSF cytokine tests, four patients had abnormal results; of these, an elevated level of IL-6 was most common, followed by IL-1 and IL-8. The most common site of involvement in cranial MRI was the brainstem and basal ganglia (60.0% respectively), followed by white matter (48.0%) and the cortex (44.0%). Nine cases (36.0%) showed lesions with enhancement and six cases (24.0%) showed mass-like lesions. Three patients (12.0%) patients had lesions in the spinal cord, most frequently in the thoracic cord. All patients received immunological intervention therapy; during follow up, the majority had a favorable outcome. Conclusions: P-NBD is an autoimmune disease with multiple system involvement and diverse clinical manifestations. The symptom of dizziness is not uncommon and can be easily ignored. Early treatment with immunotherapy is important and can improve the outcome of these patients.

[Clinical analysis of adult oculomoclonus-myoclonus syndrome with vertigo].

The clinical manifestation, physical and laboratory examination, electrophysiological, and imaging data of 2 female adult OMS patients with vertigo were analyzed at the Department of Neurology of the First Medical Center of Chinese PLA General Hospital from February 2021 to March 2022. The treatment strategy and clinical outcome were followed up. The two female patients were aged 42 and 66 years. Anti-NMDA receptor antibody and anti-GABAB receptor antibody were detected in serological screening, respectively. The two patients met the diagnostic criteria for OMS, and one was screened for breast tumor. The clinical symptoms of the two patients were relieved after immunomodulation therapy. OMS is a group of rare clinical syndromes; its clinical evaluation process should be standardized and the etiology should be actively searched for.

[Construction of a dual fluorescent reporter system for tracing horizontal transfer of mcr-1-carrying plasmid].

The green fluorescent reporter gene was inserted into the gene interval of polymyxin resistant mcr-1-carrying plasmid (pSH13G841) by homologous recombination of suicide plasmid. At the same time, E. coli J53 with red fluorescent reporter gene was constructed. Using the ability of spontaneous conjugation of drug resistant plasmid (pSH13G841), pSH13G841-GFP plasmid was transferred into J53 RFP bacteria to construct a double fluorescent labeled donor bacterium. The two light-emitting systems could stably and spontaneously express fluorescence without mutual interference. The dual fluorescence report system constructed can be used for visual tracing horizontal transfer of mcr-1-carrying plasmid, the subsequent model can study the colonization, transfer and prognosis of drug-resistant bacteria/drug-resistant genes mcr-1 by using mouse in vivo imaging technology.

[Young mammary Paget's disease patients with underlying breast invasive ductal carcinoma: clinicopathological features and prognosis].

Objective: To investigate the clinicopathological factors and prognostic status of young Mammary Paget's disease (MPD) patients with invasive ductal carcinoma (IDC). Methods: In this study, we defined the age at diagnosis below 40 years old as young patients, and retrospectively analyzed data from 123 MPD-IDC patients who were admitted at the Cancer Hospital Chinese Academy of Medical Sciences from June 2002 to February 2019. Patients were divided into the young group (≤40 years old, 15 cases) and the old group (>40 years old, 108 cases) according to the age of onset, and the clinicopathological characteristics and prognosis of the two groups were compared. Cox regression model analysis was used to analyze the prognosis influencing factors. Results: The proportions of patients in the young group with non-menopausal, axillary lymph node metastasis, and Ki-67 index ≥15% were 93.3% (14/15), 73.3% (11/15), and 86.7% (13/15), respectively, which were higher than those in the old group [45.4% (49/108), 39.8%(43/108), and 60.2% (65/108), respectively] , with statistically significant differences (P<0.05). At an average follow-up of 63.2 months, patients in the young group had a significantly shorter disease-free survival (DFS) compared with that of the old group (P=0.012), while the difference in overall survival (OS) between the two groups was not statistically significant (P=0.161). Multifactorial Cox regression analysis showed that axillary lymph node status was an independent influencing factor on OS (HR=3.339, 95% CI: 1.121-9.943) in patients with MPD-IDC, while age was not. Conclusion: Compared with the old group, young patients with MPD-IDC have a higher incidence of axillary lymph node metastasis, high Ki-67 expression, and a shorter DFS, but age is not an independent influencing factor on DFS or OS in patients with MPD-IDC.

[Correlation between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation].

Objective: To investigate the association between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation, and the independent risk factors affecting left atrial appendage function. Methods: Patients with non-valvular atrial fibrillation, who visited the Atrial Fibrillation Center of the First Affiliated Hospital of Xinjiang Medical University from June 1, 2019 to June 1, 2021, were selected. According to left atrial appendage flow velocity (LAAFV), they were divided into normal left atrial appendage function group (297 patients with LAAFV ≥ 40 cm/s) and abnormal left atrial appendage function group (85 patients with LAAFV<40 cm/s). Baseline data and transesophageal echocardiography images were collected from all the patients. The occurrence of thrombotic events was recorded. Univariate and multivariate unconditional logistic regression analyses were conducted to investigate the correlation between abnormal left atrial appendage function and the occurrence of thrombotic events. Results: There were significant differences in gender, type of atrial fibrillation, CHA2DS2-VASc score, anticoagulant therapy, total cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), left atrial diameter, proportion of patients with right atrial enlargement, left ventricular ejection fraction, inner diameter, sum of inner diameter, depth, and sum of depth of all angles of the left atrial appendage, and incidence of thrombotic events between the two groups (all P<0.05). After adjusting for confounders, multivariate unconditional logistic regression analyses showed that abnormal left atrial appendage function was closely associated with thrombotic events (ß=1.168 P=0.002), and left atrial diameter (OR=1.084, 95%CI 1.019-1.153, P=0.011) and persistent atrial fibrillation (OR=2.323, 95%CI 1.226-4.403, P=0.010) were independent risk factors affecting left atrial appendage function. Conclusions: Abnormal left atrial appendage function is closely associated with thrombosis. The left atrial diameter and persistent atrial fibrillation were independent risk factors affecting left atrial appendage function.

[PTX3 promotes proliferation, invasion and drug resistance of neuroblastoma cells in children by regulating TLR4/NF-κB signaling pathway].

Objective: To investigate the effect of pentraxin 3 (PTX3) on the proliferation, invasion and drug resistance of pediatric neuroblastoma cells and its mechanism. Methods: si-RNA (si-RNA group), si-PTX3 (si-PTX3 group), siRNA+ pcDNA3.1 (siRNA+ pcDNA3.1 group), si-PTX3+ pcDNA3.1 (si-PTX3+ pcDNA3.1 group), siRNA+ pcDNA3.1-Toll-like receptor 4 (siRNA+ pcDNA3.1-TLR4 group) and si-PTX3+ pcDNA3.1-TLR4 (si-PTX3+ pcDNA3.1-TLR4 group) were transfected into SH-SY5Y cells. Collected 32 cases of tumor tissue and cancerous tissue in children with childhood neuromaternal cells who were treated at Zhumadian center hospital from July 2016 to August 2019. Real-time fluorescent quantitative polymerase chain (RT-qPCR) reaction and immunohistochemistry experiments were used to detect the protein expressions of PTX3 in neuroblastoma tissues and normal tissues. 5-Ethynyl-2'-deoxyuridine (EdU) was used to detect the proliferation effect of PTX3 on neuroblastoma cell SH-SY5Y. Western blot experiment was used to detect the protein expression levels of vascular endothelial growth factor (VEGF), resistance-related proteins including P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), and invasion-related protein matrix metalloproteinase-1 (MMP-1). Results: PTX3 mRNA expressions in neuroblastoma tissues were 0.87±0.07, higher than 0.13±0.06 of normal tissues, and the differences were statistically significant (P<0.05), The expression of the immunohistochemistry test PTX3 protein was consistent with the qRT-PCR results. Compared with the si-RNA group (0.95±0.08; 1.02±0.10), the mRNA and protein expressions of PTX3 in the si-PTX3 group (0.25±0.05; 0.45±0.66) decreased, the differences were statistically significant (all P<0.05). The number of EdU positive cells, invasion rate, VEGF, MMP-1, P-gp and MRP-1 protein expressions in si-RNA group were (31.86±1.86)%, (28.12±2.96)%, (0.58±0.07), (0.44±0.06), (0.46±0.08) and (0.51±0.05), respectively, higher than (19.73±1.22)%, (8.45±1.06)%, (0.25±0.05), (0.19±0.03), (0.19±0.06) and (0.16±0.07) in si-PTX3 group, and the differences were statistically significant (all P<0.05). The Number of EdU positive cells [(19.49±1.68)%], invasion rate [(8.48±1.36)%], VEGF protein expression (0.10±0.15), P-gp (0.18±0.07) , TLR4 (0.45±0.06), p-p65 (0.25±0.05) protein expressions in si-PTX3+ pcDNA3.1 group were relatively lower compared with siRNA+ pcDNA3.1 group [(38.21±2.67)%, (26.39±2.14)%, 0.49±0.05, 0.52±0.06, 0.93±0.14 and 0.82±0.06] (all P<0.05). The number of EdU-positive cells [(62.73±5.18)%], invasion rate [(50.45±3.25)%], VEGF protein expression (2.17±0.17), P-gp (2.15±0.16), TLR4 (2.68±0.16), p-p65 (2.48±0.13) protein expressions in the siRNA+ pcDNA3.1-TLR4 group increased compared with siRNA+ pcDNA3.1 group (all P<0.05). Conclusions: Inhibition of PTX3 can inhibit the proliferation and invasion of neuroblastoma cells SH-SY5Y, and reduce drug resistance. Its mechanism may be achieved by regulating the TLR4/NF-κB signaling pathway. This result can provide a new perspective for pediatric neuroblasts tumor diagnosis and clinical treatment.

[Effect of silent information regulator 1 on the LPS induced lncRNA expression of macrophages in mice].

Objective: To investigate the effect of Silent information regulator 1 (Sirt1) on the expression profile of long non-coding RNA (lncRNA) in macrophages upon lipopolysaccharide (LPS) treatment. Methods: Peritoneal macrophages (PM) were isolated from nine wild-type C57BL/6 male mice (wild-type group) and nine myeloid-specific Sirt1 knock-out mice (knock-out group). RNA samples were extracted from macrophages stimulated with 1 µg/ml LPS. Sequencing and the differentially expressed lncRNA were screened after the RNA was quantified. The threshold set for up-and down-regulated genes was a fold change (wild-type group/knock-out group) ≥2 and P≤0.05. Afterwards, gene ontology (GO) and pathway enrichment analysis were conducted and co-expression network map was constructed. Results: Four hundred and forty five lncRNA genes were differentially expressed (185 lncRNA genes were up-regulated and 260 lncRNA genes were down-regulated). Two hundred mRNA genes were differentially expressed (113 mRNA genes were up-regulated and 87 mRNA genes were down-regulated). It was found that the differentially expressed lncRNA genes and the predicted corresponding target genes were mainly distributed in the regions of biological processes of macrophage inflammatory response, macrophage chemotaxis and cell metabolism by GO and pathway enrichment analysis. Conclusion: lncRNA expression profile changes significantly in LPS induced macrophages isolated from Sirt1 knock out mice, which is closely related to the function of macrophages.

[Efficacy and safety of early initiation of sacubitril-valsartan therapy in patients with acute decompensated heart failure].

Objective: To assess the efficacy and safety of the initiation of sacubitril-valsartan （ARNI） therapy, as compared with ACEI therapy, after hemodynamic stabilization among patients hospitalized for acute decompensated heart failure （ADHF）. Methods: A total of 199 hospitalized patients for ADHF in our department from January 2017 to June 2019 were included in this retrospective analysis. According to the medication early after hemodynamic stabilization, patients were divided into ARNI group (n=92) and ACEI group (n=107). Among the included patients, 61 patients with newly diagnosed heart failure at the time of admission were also divided into ARNI group (n=30) and ACEI group (n=31) according to the applied medication. Clinical baseline data and follow-up results of enrolled patients were collected through the electronic medical records at admission, outpatient and telephone follow-up. The primary effectiveness observation index was left ventricular ejection fraction (LVEF) and left ventricular end diastolic dimension (LVEDD) measured by echocardiography; the secondary observation index was death from any causes and hospitalization for heart failure. Safety outcomes were the incidences of symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema. Results: The clinical baseline characteristics were similar between ARNI group and ACEI group（all P>0.05）. The duration of follow up was (15.2±6.5) months in all patients enrolled, (12.3±5.0) months in ARNI group, and (18.2±6.5) months in ACEI group. At the end of follow-up, prevalence of an absolute LVEF increase of more than 5% was 48.9% (45/92) in ANRI group and 25.2% (27/107) in ACEI group (P=0.001). Percent of LVEF increase to more than 50% was 17.4% (16/92) in ANRI group and 3.7% (4/107) in ACEI group (P=0.001). Percent of patients with more than 10 mm LVEDD reduction was 14.1% (13/92) in ANRI group and 3.7% (4/107) in ACEI group (P=0.009). All-cause mortality rate was 5.7% (5/88) in ARNI group and 15.3% (13/85) in ACEI group (P=0.038). Rate of re-hospitalization due to heart failure was 50% (46/92) in ARNI group and 71% (76/107) in ACEI group（P=0.002）.The rates of symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema were similar between ARNI group and ACEI group (all P>0.05). In patients with first diagnosed heart failure，percent of LVEF increase to more than 50% was 30% (9/30) in ANRI group and 6.5% (2/31) in ACEI group (P=0.017). Percent of more than 10 mm LVEDD reduction was 26.7%(8/30) in ANRI group and 3.2%(1/31) in ACEI group (P=0.012). Percent of an absolute LVEF increase of more than 5% was 53.3% (16/30) in ANRI group and 51.6% (16/31) in ACEI group (P=0.893). Re-hospitalization due to heart failure was 23.3% (7/30） in ARNI group and 73.3% (11/31) in ACEI group（P<0.01）. Rate of all-cause death tended to be lower in patients receiving ARNI (3.4% (1/29)) as compared to patients receiving ACEI (13.0% (3/23), P=0.197）. Conclusions: Among patients with heart failure with reduced ejection fraction hospitalized for ADHF, the initiation of ARNI therapy after hemodynamic stabilization is associated with a more significant improvement of cardiac remodeling and pump function than ACEI therapy and satisfactory safety. In ADHF patients with first diagnosed heart failure, initiation of ARNI therapy after hemodynamic stabilization can more effectively improve cardiac remodeling and pump function than treatment with ACEI.

[One case successfully rescued acute poisoning caused by misadministration of large amount of glufosinate].

Objective: To report a case of acute glufosinate-ammonium poisoning cause respiratory cardiac arrest and grass amine poisoning cases of successful rescue. Methods: The clinical data of a case of acute glufosinate-ammonium poisoning admitted to a third-class a hospital in April 2018 were analyzed and summarized. Results: The patient was poisoned by oral administration of a large amount of glufosinate-ammonium. Respiratory and cardiac arrest occurred during treatment and resuscitation was successful Later, the nervous system showed impaired function, The patients were treated with complete gastrointestinal cleansing, hemoperfusion, and the protection of important organs. Conclusion: For a large number of patients with oral glufosinate-ammonium poisoning, we should pay close attention to the damage of nervous system while taking active and conventional detoxification treatment.

Enhanced magnetic circular dichroism by subradiant plasmonic mode in symmetric graphene oligomers at low static magnetic fields.

Giant magnetic circular dichroism (MCD) that shows a different response to incident wave with left or right-handed circular polarization under external magnetic field is promising for magneto-optical sensing, revealing symmetry and degeneracy information of electronic states. However, traditional methods and materials that are used to obtain significant MCD involve highly strong external magnetic field. Based on the excitation of subradiant plasmonic mode and Fano resonance in graphene oligomers in the mid-infrared region, we numerically demonstrate that MCD is enhanced three times larger than the previously reported method, based on the resonance of electric dipole plasmonic mode. This giant MCD is attributed to the remarkably different excitation efficiency of subdradiant plasmonic mode due to the interparticle coupling under left or right-handed circular polarization incidence and external magnetic field. Our results offer an effective mechanism to enhance MCD signal at the nanoscale, which facilitates the sensing, spintronic, nanophotonics and other such fields.

[Preliminary application value of ultrasound contrast agent with enteral nutritional suspension as mixed medium in locating indwelling nasointestinal tube in critically ill patients].

Objective: To evaluate the value of ultrasound contrast agent with enteral nutrition suspension as mixed medium in locating indwelling nasointestinal tube in critically ill patients. Methods: Total of 45 critically ill patients had nasointestinal tube indwelled were collected from June 1,2018 to April 1,2019 in the Intensive Care Unit of Zhejiang Provincial People's Hospital, including 30 males and 15 females, with an average age of (63±17) years.Enteral nutritional suspension Peptisorb Liquid was used as research medium,with the ultrasonic imaging performance of it confirmed by in vitro and in vivo experiments.The optimal mixing ratio of microbubble ultrasound contrast agent and Peptisorb Liquid was confirmed by in vitro experiment, then the mixture was quietly placed and its stability was dynamically observed. The nasointestinal tube was confirmed in the digestive tract by conventional ultrasound and then the ultrasound contrast mode turned on. Ultrasound contrast agent with Peptisorb Liquid as mixed medium was injected into the nasointestinal tube and the tube direction and end position were observed and recorded in real time. Abdominal X-ray examination or CT was used as the gold standard for verifying the location of the nasointestinal tube and the same result represented successful positioning. Results: The in vitro and in vivo experiments showed that Peptisorb Liquid had good ultrasound imaging uniformity and penetrating power, which could clearly show the range and boundary of the filling intestine cavity; the in vitro experiment showed that the ultrasound contrast agent prepared with the microbubble ultrasound contrast agent and Peptisorb Liquid by the ratio of 1∶1 000 and 1∶500 which had the best imaging effect and the best distribution uniformity, with the best stability within 10 minutes after quietly placed. Nasointestinal tubes were successfully located by using ultrasound contrast agent with enteral nutritional suspension as mixed medium in 95.6%(43/45) of the patients collected in this study,including success at one attempt in 39 cases, the operating time was (1.6±0.5) minutes and 4 cases were successfully located after multiple operations with (5.1±0.5) minutes, the tube bent in the stomach in one case and flexed back into the stomach from the descending duodenum in another. The operation failed in 2 cases (4.4%). No significant complications occurred during the examination. Conclusion: The ultrasound contrast agent with enteral nutritional suspension as mixed medium has the advantages of both, which can conveniently, safely and effectively locate the direction and end position of nasointestinal tube in critically ill patients.

Trastuzumab combined with doublet or single-agent chemotherapy as first-line therapy for HER2-positive metastatic breast cancer.

PURPOSE: To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). METHODS: We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766. RESULTS: The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63-0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88-0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98-1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H. CONCLUSIONS: Compared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.

Broadband reflective lens in visible band based on aluminum plasmonic metasurface.

We demonstrate a flat optical lens based on plasmonic reflectarray metasurface, which consists of a planar array of hyperbolic-shaped aluminum (Al) nanoantenna separated from an Al ground plane by a SiO2 spacer. The gradual change in the width of the Al nanoantenna enables unique broadband (400-700 nm) to focus on the visible band because of its hyperbolic reflection-phase profile. The focal length of metalens is quickly decreased with the increase of wavelength in the short wavelength region (400-550 nm), compensating the chromatic aberration in traditional lenses. In long wavelength region (550-700 nm), the focal length has only a slight change, thereby minimizing chromatic aberration. Furthermore, the proposed metalens creates a small focal spot beyond diffraction limit, while maintaining high focusing efficiency. Our method of simple and anisotropic nanoantenna is used to realize wide phase tuning range offers a novel strategy to design braodband metalens, and our metalens has widespread applications in compact camera, telescope, and microscope.

Long-term effects: Galectin-1 and specific immunotherapy for allergic responses in the intestine.

BACKGROUND AND AIMS: Mast cell activation interferes with the effects of allergen-specific immunotherapy (SIT). Galectin-1 (Gal-1) is capable of regulating immune cells' functions. This study tests the hypothesis that administration of Gal-1 promotes and prolongs the efficacy of SIT via suppressing mast cell activation. METHODS: An intestinal allergy mouse model was developed. The coadministration of SIT and Gal-1 on suppression of the allergic responses, prevention of mast cell activation, and generation of antigen-specific regulatory T cells (Treg) in the intestine was observed in sensitized mice. RESULTS: The coadministration of Gal-1 and SIT markedly suppressed the allergic responses in the mouse intestine vs the use of either SIT alone or Gal-1 alone. The Gal-1 binds to the IgE/FcɛRI complexes on the surface of mast cells to prevent mast cell activation during SIT. Gal-1 promoted the SIT-generated allergen-specific Tregs in the intestine of sensitized mice. Coadministration of Gal-1 and SIT significantly enhanced the efficacy of immunotherapy in suppressing allergic responses in the intestine, which lasted for at least for 12 months. CONCLUSIONS: Long-term effects of specific immunotherapy on intestinal allergy can be achieved with Gal-1/SIT therapy by inhibiting mast cell activation and facilitating Treg development.

Dust mite allergen, glutathione S-transferase, induces T cell immunoglobulin mucin domain-4 in dendritic cells to facilitate initiation of airway allergy.

BACKGROUND: Allergens from dust mites play a critical role in the pathogenesis of airway allergy. The mechanism by which dust mite allergens induce allergic diseases is not fully understood yet. OBJECTIVE: This study tests a hypothesis that the eighth subtypes of Dermatophagoides farina allergen (Derf8) play an important role in the induction of airway allergy. METHODS: The protein of Derf8 was synthesized via molecular cloning approach. Dendritic cells (DC) were stimulated with Derf8 in the culture, and then, the expression of T cell immunoglobulin mucin domain 4 (TIM4) in dendritic cells (DC) was analysed. The role of Derf8 in the induction of airway allergy was evaluated with a mouse model. RESULTS: Exposure to Derf8 markedly induced the TIM4 expression in DCs by modulating the chromatin at the TIM4 promoter locus. Derf8 played a critical role in the expansion of the T helper 2 response in the mouse airway via inducing DCs to produce TIM4. Administration with Derf8-depleted dust mite extracts (DME) inhibited the allergic inflammation and induced regulatory T cells in mice with airway allergy. CONCLUSION: Derf8 plays an important role in the initiation of dust mite allergy. Vaccination with Derf8-deficient DME is more efficient to inhibit the dust mite allergic inflammation than using wild DME.

Down-regulated expression of Tim-3 promotes invasion and metastasis of colorectal cancer cells.

To explore how Tim-3 is expressed and how its expression influences invasion and metastasis of colorectal cancer (CRC) cells. A total of 188 CRC patients were prospectively collected for this study. Meanwhile, 135 normal controls were incorporated during the same period. Intestinal samples of the CRC radical cancerous tissues, paracancerous tissues ( 5.0 cm beyond the cancer tissue) were collected for the following experiment. Furthermore, peripheral venous blood samples (10 ml) were collected from each subject. Immunohistochemical analysis, quantitative real-time polymerase chain reaction (RT-qPCR) and western blot were performed for the detection of Tim-3 in different tissues. The immunohistochemical staining results showed that a positive Tim-3 signal was localized in the cytoplasm and nucleus, observed as yellow or brown granules. Tim-3 was largely expressed in colon carcinoma tissues and normal colon mucosa tissues but was rarely expressed in the cell membrane. RT-qPCR results indicated that Tim-3 mRNA levels were significantly lower in CRC tissues than in paracancerous tissues and normal colon mucosa tissues. A trend of decreased Tim-3 mRNA levels was also found in the paracancerous tissues compared with the normal colon mucosa tissues (all P < 0.05). Western blot results revealed reduced Tim-3 protein expression in CRC tissues compared with normal colon mucosa tissues and paracancerous tissues, and Tim-3 protein expression was much lower in the paracancerous tissues than in the normal colon mucosa tissues (all P < 0.05). Furthermore, obviously lower Tim-3 mRNA levels were found in the poorly differentiated CRC patients and in those with lymph node metastasis and distant metastasis (all P < 0.05). Collectively, Tim-3 expression was mainly located in the cytoplasm and nucleus, showing down-regulated expression in colon carcinoma tissues compared with normal and paracancerous tissues. Reduced Tim-3 expression may promote CRC invasion and metastasis providing a medical reference for the treatment of CRC.

[Analysis of the clinicopathological characteristics and prognosis in 674 cases of breast intraductal papillary tumor].

Objective: Breast intraductal papillary tumors are clinically common diseases derived from the ducts. The aim of this study is to investigate the clinicopathological characteristics of intraductal papillary tumors and risk factors for carcinogenesis. Methods: The clinicopathological data of 674 patients with breast intraductal papillary tumors, who underwent surgery in the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences from January 2010 to July 2015, were retrospectively analyzed. Results: The median follow-up time was 46 months. The 674 cases were classified into 547 intraductal papilloma, 88 cases of intraductal papillary carcinoma, 32 cases of intracystic papillary carcinoma, and 7 cases of solid papillary carcinoma of breast. After a median follow-up time of 46 months, 13 out of 547 (2.4%) intraductal papillomas had local recurrence in the original dissected quadrat, another 10 cases developed breast cancer in the original dissected quadrat. The 3-year recurrence-free survival rates in intraductal papilloma and intraductal papilloma accompanied with atypical ductal hyperplasia were 97.7% and 93.5%, respectively, the recurrence-free survival curves showed a significant difference (P=0.011). Multivariate analysis indicated that atypical ductal hyperplasia was a major prognostic factor affecting the recurrence-free survival of intraductal papilloma (RR=0.183, 95%CI=0.054 to 0.777, P=0.020). Four cases (3.1%) of intraductal papillary carcinoma had local recurrence. The logistic analysis showed that patient aged >45 years, clinical manifestations of a breast lump, maximum tumor diameter greater than 2 cm are possible clinical manifestation of malignant breast intraductal papillary tumors (RR=1.735, 95%CI=1.007-2.990, P=0.047; RR=2.849, 95%CI=1.207-6.711, P=0.017; RR=3.792, 95%CI=2.162-6.653, P<0.001). Conclusions: Intraductal papillary tumors have a certain recurrence rate. Age, clinical features and tumor size may be predictive factors of intraductal papillary carcinoma.

[Clinical application of Acutegastrointestinal injury grading system assocaited with clinical severity outcome in critically ill patients: a multi-center prospective, observational study].

Objective: To investigate the feasibility of utilizing the current acute gastrointestinal injury(AGI) grading system, and explore the association of severity of AGI grade with clinical outcome in critically ill patients. Methods: The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24 h were recruited, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed based on GIsymptoms, feeding details and organ dysfunctionon the first week of admission to ICU.The intra-abdominal pressures(IAP) was measured using AbViser device. Results: Of 550 patients enrolled, mean values for age and APACHE Ⅱ score were (64.9±17.2) years and (19.5±7.4), respectively. 456 patients(82.9%) took mechanical ventilation, and 470 patients were identified for AGI. The distribution of AGI grade on the frist day of ICU admission were 50.6%(Ⅰ grade, n=238), 34.2%(Ⅱ grade, n=161), 12.4%(Ⅲ grade, n=58) and 2.8%(Ⅳ, n=13), respectively, while the distribution of the global AGI grade based on the 7-day AGI assessment of ICU admission were 24.5%(Ⅰ grade, n=115), 49.4%(Ⅱ grade, n=232), 20.6%(Ⅲ grade, n=97) and 5.5%(Ⅳ, n=26), respectively. 28- and 60-day mortality rate was 29.3%(n=161) and 32.5%(n=179), respectively. The patients with AGI had a higher 28-(31.1% vs 18.8%, P=0.025) and 60-day survival rate(34.7% vs 20.0%, P=0.01) than those with non-AGI, and also there were positive correlations between AGI grade and 28- and 60-day mortality(P<0.001). Univariate Cox regression analysis showed that age, the source of medicial admission, diabetes mellitus, coronary heart disease, the use of vasoactive drugs, serum creatinine and lactate, mechanical ventilation, APACHE Ⅱ score, the AGI grade in the first day of ICU admission and feeding intolerance within the first week of ICU stay were significantly(P≤0.02) associated with mortality. In multivariate analysis including all these variables, the source of medical admission(χ(2)=4.34, P=0.04), diabete mellitus(χ(2)=3.96, P=0.05), the use of vasoactive drugs(χ(2)=6.55, P=0.01), serum lactate(χ(2)=4.73, P=0.03), the global AGI grade in the 7-day of ICU admission(χ(2)=7.10, P=0.008), and APACHE Ⅱ score(χ(2)=12.1, P<0.001) remained independent predictors for 60-day mortality.In the further subgroup analysis including 402 patients with 7-day survival, the feeding intolerance within the first week of ICU stay could provide independent and incremental prognostic value of 60-day mortality wtih increased χ(2)value of Cox regression model(χ(2)=52.2 vs 41.9, P=0.007) . Conclusion: The AGI grading system is useful for identifying the severity of gastrointestinal dysfunction, and could be used as a strong predictor of impaired outcome. The results provide evidence to support that feeding intolerance within 7 days of admission to ICU was an independent determinant of mortality.

High-Brightness High-Energy Electron Beams from a Laser Wakefield Accelerator via Energy Chirp Control.

By designing a structured gas density profile between the dual-stage gas jets to manipulate electron seeding and energy chirp reversal for compressing the energy spread, we have experimentally produced high-brightness high-energy electron beams from a cascaded laser wakefield accelerator with peak energies in the range of 200-600 MeV, 0.4%-1.2% rms energy spread, 10-80 pC charge, and ∼0.2 mrad rms divergence. The maximum six-dimensional brightness B_{6D,n} is estimated as ∼6.5×10^{15} A/m^{2}/0.1%, which is very close to the typical brightness of e beams from state-of-the-art linac drivers. These high-brightness high-energy e beams may lead to the realization of compact monoenergetic gamma-ray and intense coherent x-ray radiation sources.