NSUN2/YBX1 promotes the progression of breast cancer by enhancing HGH1 mRNA stability through m5C methylation.

BACKGROUND: RNA m5C methylation has been extensively implicated in the occurrence and development of tumors. As the main methyltransferase, NSUN2 plays a crucial regulatory role across diverse tumor types. However, the precise impact of NSUN2-mediated m5C modification on breast cancer (BC) remains unclear. Our study aims to elucidate the molecular mechanism underlying how NSUN2 regulates the target gene HGH1 (also known as FAM203) through m5C modification, thereby promoting BC progression. Additionally, this study targets at preliminarily clarifying the biological roles of NSUN2 and HGH1 in BC. METHODS: Tumor and adjacent tissues from 5 BC patients were collected, and the m5C modification target HGH1 in BC was screened through RNA sequencing (RNA-seq) and single-base resolution m5C methylation sequencing (RNA-BisSeq). Methylation RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA-binding protein immunoprecipitation-qPCR (RIP-qPCR) confirmed that the methylation molecules NSUN2 and YBX1 specifically recognized and bound to HGH1 through m5C modification. In addition, proteomics, co-immunoprecipitation (co-IP), and Ribosome sequencing (Ribo-Seq) were used to explore the biological role of HGH1 in BC. RESULTS: As the main m5C methylation molecule, NSUN2 is abnormally overexpressed in BC and increases the overall level of RNA m5C. Knocking down NSUN2 can inhibit BC progression in vitro or in vivo. Combined RNA-seq and RNA-BisSeq analysis identified HGH1 as a potential target of abnormal m5C modifications. We clarified the mechanism by which NSUN2 regulates HGH1 expression through m5C modification, a process that involves interactions with the YBX1 protein, which collectively impacts mRNA stability and protein synthesis. Furthermore, this study is the first to reveal the binding interaction between HGH1 and the translation elongation factor EEF2, providing a comprehensive understanding of its ability to regulate transcript translation efficiency and protein synthesis in BC cells. CONCLUSIONS: This study preliminarily clarifies the regulatory role of the NSUN2-YBX1-m5C-HGH1 axis from post-transcriptional modification to protein translation, revealing the key role of abnormal RNA m5C modification in BC and suggesting that HGH1 may be a new epigenetic biomarker and potential therapeutic target for BC.

Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway.

BACKGROUND: RNA cargo in exosomes, especially microRNAs (miRNAs), play an important role in the chemotherapy drug resistance of human cancers. However, the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study, we sought to explore whether exosomal miR-107 could reverse the resistance of gastric cancer cells to the chemotherapy drugs. METHODS: We extracted exosomes from sensitive (SGC-7901, MGC-803) and resistant (SGC-7901/5-FU) gastric cancer cells by ultracentrifugation and the isolated exosomes were identified using transmission electron microscopy (TEM) and dynamic light scattering analysis (DLS). The expression of miR-107 and high mobility group A2 (HMGA2) were detected by real-time quantitative PCR (RT-qPCR). MTT assay was used to investigate the effect of exosomes on gastric cancer cells growth in vitro. The uptake of exosomes by recipient cells were observed using a fluorescence microscope. The predicted target relationship between miR-107 and HMGA2 was verified by gauss-luciferase reporter assay. The expression of HMGA2, p-mTOR/mTOR, P-gp and other exosomal indicated marker proteins was detected by western blot. RESULTS: Our results indicated that the isolated exosomes were typically cup-like lipid bilayer membranes structure. SGC-7901/5-FU cells were cross-resistant to chemotherapy drug cisplatin (CDDP), and the sensitive cells-secreted exosomes drastically reversed the resistance of the resistant GC cells to the chemotherapeutic drugs, which was verified by exosomal inhibitor GW4896. Mechanistically, the reversal effect was mainly mediated by exosome-secreted miR-107 through downregulating the expression of target molecular HMGA2 and inhibiting HMGA2/mTOR/P-gp pathway, which were supported by results from luciferase reporter assay and rescue assay. CONCLUSIONS: These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and exosomal miR-107 may be a novel target in gastric cancers treatment.

Left ventricular systolic dysfunction in patients with unprotected left main coronary artery disease.

BACKGROUND: The optimal coronary revascularization strategy for patients with unprotected left main coronary artery (ULMCA) disease and left ventricular systolic dysfunction (LVSD) remains uncertain. The purpose of this study was to evaluate the clinical outcomes after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) versus coronary artery bypass grafting (CABG) in patients with ULMCA disease with or without LVSD. METHODS: A total of 984 patients with ULMCA disease who received a DES (n = 511) or underwent CABG (n = 473) were included in this study. We retrospectively analyzed the clinical parameters and outcomes of ULMCA disease patients with different left ventricular ejection fraction levels. RESULTS: There were no significant differences in major adverse cardiac and cerebral events, all-cause death, cardiac death, myocardial infarction, or stroke between the CABG and DES groups with or without LVSD. The rate of target vessel revascularization was significantly higher with DES compared with CABG in patients without LVSD; however, the difference was not significant between the mild LVSD and severe LVSD groups. CONCLUSION: For patients with ULMCA disease and LVSD, there was no significant difference between DES and CABG in terms of efficacy and safety. Treatment with DES was an acceptable alternative to CABG.

The Complement C3a-C3aR Axis Promotes Development of Thoracic Aortic Dissection via Regulation of MMP2 Expression.

Thoracic aortic dissection (TAD), once ruptured, is devastating to patients, and no effective pharmaceutical therapy is available. Anaphylatoxins released by complement activation are involved in a variety of diseases. However, the role of the complement system in TAD is unknown. We found that plasma levels of C3a, C4a, and C5a were significantly increased in patients with TAD. Elevated circulating C3a levels were also detected in the developmental process of mouse TAD, which was induced by ß-aminopropionitrile monofumarate (BAPN) treatment, with enhanced expression of C1q and properdin in mouse dissected aortas. These findings indicated activation of classical and alternative complement pathways. Further, expression of C3aR was obviously increased in smooth muscle cells of human and mouse dissected aortas, and knockout of C3aR notably inhibited BAPN-induced formation and rupture of TAD in mice. C3aR antagonist administered pre- and post-BAPN treatment attenuated the development of TAD. We found that C3aR knockout decreased matrix metalloproteinase 2 (MMP2) expression in BAPN-treated mice. Additionally, recombinant C3a stimulation enhanced MMP2 expression and activation in smooth muscle cells that were subjected to mechanical stretch. Finally, we generated MMP2-knockdown mice by in vivo MMP2 short hairpin RNA delivery using recombinant adeno-associated virus and found that MMP2 deficiency significantly reduced the formation of TAD. Therefore, our study suggests that the C3a-C3aR axis contributes to the development of TAD via regulation of MMP2 expression. Targeting the C3a-C3aR axis may represent a strategy for inhibiting the formation of TAD.

Simple and effective calculations about spectral power distributions of outdoor light sources for computer vision.

The spectral power distributions (SPD) of outdoor light sources are not constant over time and atmospheric conditions, which causes the appearance variation of a scene and common natural illumination phenomena, such as twilight, shadow, and haze/fog. Calculating the SPD of outdoor light sources at different time (or zenith angles) and under different atmospheric conditions is of interest to physically-based vision. In this paper, for computer vision and its applications, we propose a feasible, simple, and effective SPD calculating method based on analyzing the transmittance functions of absorption and scattering along the path of solar radiation through the atmosphere in the visible spectrum. Compared with previous SPD calculation methods, our model has less parameters and is accurate enough to be directly applied in computer vision. It can be applied in computer vision tasks including spectral inverse calculation, lighting conversion, and shadowed image processing. The experimental results of the applications demonstrate that our calculation methods have practical values in computer vision. It establishes a bridge between image and physical environmental information, e.g., time, location, and weather conditions.

Dual Regression-Enhanced Gaze Target Detection in the Wild.

Gaze is a vital feature in analyzing natural human behavior and social interaction. Existing gaze target detection studies learn gaze from gaze orientations and scene cues via a neural network to model gaze in unconstrained scenes. Though achieve decent accuracy, these studies either employ complex model architectures or leverage additional depth information, which limits the model application. This article proposes a simple and effective gaze target detection model that employs dual regression to improve detection accuracy while maintaining low model complexity. Specifically, in the training phase, the model parameters are optimized under the supervision of coordinate labels and corresponding Gaussian-smoothed heatmap labels. In the inference phase, the model outputs the gaze target in the form of coordinates as prediction rather than heatmaps. Extensive experimental results on within-dataset and cross-dataset evaluations on public datasets and clinical data of autism screening demonstrate that our model has high accuracy and inference speed with solid generalization capabilities.

Blood clot and fibrin recognition method for serum images based on deep learning.

BACKGROUND: Detecting and identifying of clots and fibrins in serum is an important process in the analysis stage before laboratory analysis. Currently, visual examination is commonly employed in clinical laboratories for this purpose. However, this method is not only time-consuming but also highly subjective and may result in misjudgments. METHOD: A serum image blood clot and fibrin segmentation method based on improved UNeXt was proposed. The improved UNeXt segmentation network was used to train the self-built serum dataset, and the trained model was used for blood clot and fibrin segmentation in serum images. Whether the serum images contained blood clots and fibrins was identified according to the segmentation results. RESULTS: The average Dice coefficient of the serum image segmentation network output was 0.8707, which realized more accurate segmentation of blood clots and fibrins in serum images. In 13,230 clinical serum samples, the sensitivity, specificity, and accuracy of blood clot and fibrins segmentation in serum images were 95.74%, 98.11% and 97.93%, respectively, which meet clinical test requirements. CONCLUSIONS: The improved UNeXt segmentation network rapidly and accurately segmented and recognized blood clots and fibrins in serum images, which provided an accurate basis for the sampling height of the sampling needle in the automated biochemical and immunological assembly line.

Nonocclusive mesenteric ischemia after percutaneous kyphoplasty: A case report.

RATIONALE: Percutaneous kyphoplasty (PKP) is a minimally invasive technique employed for treating vertebral compression fractures. Although PKP is simple and relatively safe, severe complications are possible. Here, we report a new, severe complication linked to this procedure, namely nonocclusive mesenteric ischemia (NOMI). PATIENT CONCERNS: An 83-year-old female patient, previously in good health, fell backward, landing on her buttocks, and subsequently experienced persistent low-back pain that exacerbated during turning or sitting up. DIAGNOSES: Lumbar spine radiography revealed wedge deformity of the L1 vertebral body. Lumbar spine magnetic resonance imaging indicated a fresh compression fracture of the L1 vertebral body. INTERVENTIONS: On the 2nd day following the trauma, the patient underwent PKP under local anesthesia. Anesthesia was satisfactory, and the procedure progressed smoothly. OUTCOMES: The patient experienced mild discomfort in the right abdomen within the 1st hour to 3 days postoperatively, mild abdominal distension on the 4th day, and sudden severe abdominal pain on the 5th day. Immediate abdominal computed tomography revealed ischemic changes in the ascending colon and hepatic flexure, accompanied by hepatic portal venous gas. An hour later, abdominal pain spontaneously subsided. Approximately 5 hours later, an enhanced abdominal computed tomography revealed no filling defects in the mesenteric vasculature, absence of luminal narrowing or occlusion, enhanced intestinal walls, and a notable improvement in hepatic portal venous gas. Considering NOMI and ischemia related to superior mesenteric artery spasm, vasodilator therapy (papaverine hydrochloride) was initiated, leading to favorable outcomes. On day 17, pathological examination of the hepatic flexure revealed moderate, acute, and chronic mucosal inflammation, along with interstitial fibrous tissue proliferation, providing clear evidence supporting ischemic changes. She was discharged on day 18 after a successful recovery. LESSONS: The occurrence of NOMI after PKP is uncommon. Yet, once it happens, delayed diagnosis or misdiagnosis can lead to serious consequences such as intestinal necrosis and abdominal infection, even endangering the patient's life. We currently lack experience in preventing this complication, but timely diagnosis and appropriate intervention are effective measures in treating such complications.

Research progress on exosomal proteins as diagnostic markers of gastric cancer (review article).

Gastric cancer (GC) is one of the most common types of tumors and the most common cause of cancer mortality worldwide. The diagnosis of GC is critical to its prevention and treatment. Available tumor markers are the crucial step for GC diagnosis. Recent studies have shown that proteins in exosomes are potential diagnostic and prognostic markers for GC. Exosomes, secreted by cells, are cup-shaped with a diameter of 30-150 nm under the electron microscope. They are also surrounded by lipid bilayers and are widely found in various body fluids. Exosomes contain proteins, lipids and nucleic acid. The examination of exosomal proteins has the advantages of quickness, easy sampling, and low pain and cost, as compared with the routine inspection method of GC, which may lead to marked developments in GC diagnosis. This article summarized the exosomal proteins with a diagnostic and prognostic potential in GC, as well as exosomal proteins involved in GC progression.

Role of chemokines in the crosstalk between tumor and tumor-associated macrophages.

Tumor microenvironment (TME) consists of a dynamic network of non-tumoral stromal cells, including cancer-associated fibroblasts, endothelial cells, tumor-associated macrophages (TAMs), B and T cells. In the TME, TAMs support tumor initiation, progression, invasion and metastasis by promoting angiogenesis and immunosuppression of the tumor cells. There is close crosstalk between TAMs and tumor cells. Notably, chemokines are a significant messenger mediating the crosstalk between tumor cells and TAMs. TAMs can promote tumor progression via secretion of chemokines. Various chemokines secreted by tumors are involved in the generation and polarization of TAMs, the infiltration of TAMs in tumors, and the development of TAMs' suppressive function. This paper reviews CCL2-CCR2, CCL3/5-CCR5, CCL15-CCR1, CCL18-CCR8, CX3CL1/CCL26-CX3CR1, CXCL8-CXCR1/2, CXCL12-CXCR4/CXCR7 signaling pathways, their role in the recruitment, polarization and exertion of TAMs, and their correlation with tumor development, metastasis and prognosis. Furthermore, we present the current research progress on modulating the effects of TAMs with chemokine antagonists and discuss the prospects and potential challenges of using chemokine antagonists as therapeutic tools for cancer treatment. The TAMs targeting by chemokine receptor antagonists in combination with chemotherapy drugs, immune checkpoint inhibitors or radiotherapy appears to be a promising approach.

An improved method for rapid identification of hook effect samples in HBsAg quantitative assay.

Quantitative hepatitis B surface antigen assay is widely used for diagnosis of hepatitis B virus infection; however, specimens with high levels of the antigen can cause false-negative results (Hook effect), which needs to be resolved. The hook effect samples and non-hook effect samples were detected on the LiCA® 500 instrument using three methods, viz., 1, 2, and 3. Method 1, the currently used procedure, was performed in two steps with a total reaction time of 25 min in a final volume of 250 µL: first incubation was with two reagents for 15 min and then with one other reagent for 10 min. In Method 2, all three reagents were added in one step with a final volume of 250 µL, and the total reaction time was still 25 min. In Method 3, the improved method, all three reagents were added in one step while the final volume was only 130 µL and the total reaction time was only 1 min. Signal values of the non-hook effect samples obtained using Method 2 were significantly lower than those with Method 1, showing competitive inhibition. The hook effect samples tested with Method 2 approximated those obtained using Method 1. Method 3 took 1 min and differentiated hook effect samples successfully, similar to the results with Method 2 which took 25 min. Changing the timing of one reagent addition and incubation time in Method 3 provided a rapid and effective method for the identification of hook effect. The results were more clearly distinguishable due to the phenomenon of competitive inhibition. Method 3 can be considered an improvement on the chemiluminescence platform.

Role of myeloid-derived suppressor cells in the formation of pre-metastatic niche.

Metastasis is a complex process, which depends on the interaction between tumor cells and host organs. Driven by the primary tumor, the host organ will establish an environment suitable for the growth of tumor cells before their arrival, which is called the pre-metastasis niche. The formation of pre-metastasis niche requires the participation of a variety of cells, in which myeloid-derived suppressor cells play a very important role. They reach the host organ before the tumor cells, and promote the establishment of the pre-metastasis niche by influencing immunosuppression, vascular leakage, extracellular matrix remodeling, angiogenesis and so on. In this article, we introduced the formation of the pre-metastasis niche and discussed the important role of myeloid-derived suppressor cells. In addition, this paper also emphasized the targeting of myeloid-derived suppressor cells as a therapeutic strategy to inhibit the formation of pre-metastasis niche, which provided a research idea for curbing tumor metastasis.

Exosomal targeting and its potential clinical application.

Exosomes are extracellular vesicles secreted by a variety of living cells, which have a certain degree of natural targeting as nano-carriers. Almost all exosomes released by cells will eventually enter the blood circulation or be absorbed by other cells. Under the action of content sorting mechanism, some specific surface molecules can be expressed on the surface of exosomes, such as tetraspanins protein and integrin. To some extent, these specific surface molecules can fuse with specific cells, so that exosomes show specific cell natural targeting. In recent years, exosomes have become a drug delivery system with low immunogenicity, high biocompatibility and high efficacy. Nucleic acids, polypeptides, lipids, or small molecule drugs with therapeutic function are organically loaded into exosomes, and then transported to specific types of cells or tissues in vivo, especially tumor tissues, to achieve targeting drug delivery. The natural targeting of exosome has been found and recognized in some studies, but there are still many challenges in effective clinical treatments. The use of the natural targeting of exosomes alone is incapable of accurately transporting the goods loaded to specific sites. Besides, the natural targeting of exosomes is still an open question in disease targeting and efficient gene/chemotherapy combined therapy. Engineering transformation and modification on exosomes can optimize its natural targeting and deliver the goods to a specific location, providing wide use in clinical treatment. This review summarizes the research progress of exosomal natural targeting and transformation strategy of obtained targeting after transformation. The mechanism of natural targeting and obtained targeting after transformation are also reviewed. The potential value of exosomal targeting in clinical application is also discussed.

Viral resistance to VRC01-like antibodies with mutations in loop D and V5 from an HIV-1 B' subtype infected individual with broadly neutralization activity.

Recently we identified the VRC01-like antibody DRVIA7(A7) from an HIV-1 B' subtype-infected individual (DRVI01) with broad neutralization activity, and almost all viruses from the individual were resistant to both VRC01 and A7 lineage antibodies. Here, we identified and characterized a panel of HIV-1 variants with resistance to VRC01 and A7 using site-directed mutagenesis and swapping amino acid fragments of gp120. Site-directed mutagenesis revealed that E279D/R282K/N460A/T464N of gp120 from DRVI01 produced VRC01-susceptible variants. Multiple mutations significantly increased the neutralization sensitivity to VRC01. Residues N464 located at the tip of the V5 loop were considered irrelevant to the neutralization of VRC01. For DRVI01-derived viruses, the single N464T change fully produced VRC01-resistant variants; conversely, a single T464N mutation generated VRC01-susceptible variants. Alanine scanning revealed that the N464 residue plays a vital role in binding with VRC01. Neutralizing assays against A7 lineage antibodies showed that DRVI01-derived viruses with multiple mutations could be neutralized by A7 lineage antibodies with different neutralizing breadths. Combining the changes in loops D and V5 produced variants that were totally sensitive variants to A7 lineage antibodies.

Factors associated with neutralizing antibody levels induced by two inactivated COVID-19 vaccines for 12 months after primary series vaccination.

Background: BBIBP-CorV and CoronaVac inactivated COVID-19 vaccines are widely-used, World Health Organization-emergency-listed vaccines. Understanding antibody level changes over time after vaccination is important for booster dose policies. We evaluated neutralizing antibody (nAb) titers and associated factors for the first 12 months after primary-series vaccination with BBIBP-CorV and CoronaVac. Methods: Our study consisted of a set of cross-sectional sero-surveys in Zhejiang and Shanxi provinces, China. In 2021, we enrolled 1,527 consenting 18-59-year-olds who received two doses of BBIBP-CorV or CoronaVac 1, 3, 6, 9, or 12 months earlier and obtained blood samples and demographic and medical data. We obtained 6-month convalescent sera from 62 individuals in Hebei province. Serum nAb titers were measured by standard micro-neutralization cytopathic effect assay in Vero cells with ancestral SARS-CoV-2 strain HB01. We used the first WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (NIBSC code 20/136) to standardized geometric mean concentrations (IU/mL) derived from the nAb geometric mean titers (GMT over 1:4 was considered seropositive). We analyzed nAb titer trends using Chi-square and factors related to nAb titers with logistic regression and linear models. Results: Numbers of subjects in each of the five month-groupings ranged from 100 to 200 for each vaccine and met group-specific target sample sizes. Seropositivity rates from BBIBP-CorV were 98.0% at 1 month and 53.5% at 12 months, and GMTs were 25.0 and 4.0. Respective seropositivity rates from CoronaVac were 90.0% and 62.5%, and GMTs were 20.2 and 4.1. One-, three-, six-, nine-, and twelve-month GMCs were 217.2, 84.1, 85.7, 44.6, and 10.9 IU/mL in BBIBP-CorV recipients and 195.7, 94.6, 51.7, 27.6, and 13.4 IU/mL in CoronaVac recipients. Six-month convalescent seropositivity was 95.2%; GMC was 108.9 IU/mL. Seropositivity and GMCs were associated with age, sex, and time since vaccination. Conclusions: Neutralizing Ab levels against ancestral SARS-CoV-2 from BBIBP-CorV or CoronaVac vaccination were similar and decreased with increasing time since vaccination; over half of 12-month post-vaccination subjects were seropositive. Seropositivity and GMCs from BBIBP-CorV and CoronaVac six and nine months after vaccination were similar to or slightly lower than in six-month convalescent sera. These real-world data suggest necessity of six-month booster doses.

[Influence of granulocyte colony stimulating factor on distribution of bone marrow stem cells and its role in protecting brain in rats with cerebral ischemia].

OBJECTIVE: To explore the influence of recombination granulocyte colony stimulating factor (rG-CSF) on mobilization and distribution of bone marrow stem cells (BMSCs) in blood and brain tissue, and its role in protecting brain in rats with cerebral ischemia. METHODS: One hundred and six Sprague-Dawley (SD) rats were divided into sham-operated group (n=10),model group (n=48), rG-CSF group (n=48) according to the method of random digital table, and rats in model and rG-CSF groups were divided into four subgroups: i.e. 2, 3, 7 and 14 days subgroups, with 12 rats in each subgroup. Middle cerebral artery occlusion (MCAO) model was reproduced with nylon thread. In rats of rG-CSF group rG-CSF (10 µg/kg) was administered by subcutaneous injection 3 days before and 2 days after operation respectively, once a day. Rats in sham-operated and model groups were administered with normal saline in the same volume, once a day. At the corresponding time after operation, general neural function score (GNFS) of rats was measured. Blood was collected through abdominal aorta, then white blood cell (WBC) and CD34+ cells in peripheral blood were counted. Brain pathologic changes were observed, and expression of CD34+ cells in rats brain tissue was determined by using immunohistochemical method. RESULTS: (1) GNFS was lower obviously in 2-day model group compared with that in sham-operated group, and then increased gradually. At 7 days and 14 days after operation, GNFS in rG-CSF group was higher significantly than that in model group (7 days: 11.86±0.69 vs. 10.53±0.76, 14 days: 13.38±0.52 vs. 12.38±0.52, both P<0.01). (2) WBC and CD34+ cells in peripheral blood in model group increased obviously, with the highest level appeared at 3 days and lowered at 7 days and 14 days. Increase of WBC and CD34+ cells in rats of rG-CSF group was more obvious than that of model group at each time point except CD34+ in 14 days group [WBC (×10(9)/L) 2 days: 11.75±1.76 vs. 8.07±1.27, 3 days: 13.07±1.70 vs. 10.88±1.78, 7 days: 8.63±1.36 vs. 5.58±1.57, 14 days: 6.98±0.98 vs. 4.87±0.92; CD34+ (cells/µl) 2 days: 8.83±2.14 vs. 3.17±0.75, 3 days: 13.50±1.87 vs. 5.00±1.55, 7 days: 5.33±1.21 vs. 2.33±1.21, P<0.05 or P<0.01]. (3) Expression of CD34+ cells in the brain of rats in 2-day model group increased significantly, and the highest level appeared at 7 days and decreased at 14 days. Absorbance (A) value of CD34+ cells expression in rat brains of each rG-CSF group was more significant than that in model group (2 days: 43.21±4.41 vs. 22.04±2.95, 3 days: 45.79±1.76 vs. 25.69±2.44, 7 days: 52.09±2.86 vs. 33.04±2.62, 14 days: 29.73±1.99 vs. 16.91±2.95, all P<0.01). (4) The signs of injury to brain in pathological examination were less obvious in 14 days rG-CSF group. CONCLUSION: BMSCs could be induced to enter peripheral blood and "home" to brain tissue after cerebral ischemia. It was showed that BMSCs increased in number at first and then decreased in peripheral blood and brain, the peak number was found on 3rd day in peripheral blood and 7th day in brain. Mobilization with rG-CSF could increase the number of BMSCs in peripheral blood and brain tissue. The effect of mobilization of BMSCs on protecting brain was significant after cerebral ischemia, and effect appeared to be more pronounced with prolongation of mobilization.

Tracking-by-Counting: Using Network Flows on Crowd Density Maps for Tracking Multiple Targets.

State-of-the-art multi-object tracking (MOT) methods follow the tracking-by-detection paradigm, where object trajectories are obtained by associating per-frame outputs of object detectors. In crowded scenes, however, detectors often fail to obtain accurate detections due to heavy occlusions and high crowd density. In this paper, we propose a new MOT paradigm, tracking-by-counting, tailored for crowded scenes. Using crowd density maps, we jointly model detection, counting, and tracking of multiple targets as a network flow program, which simultaneously finds the global optimal detections and trajectories of multiple targets over the whole video. This is in contrast to prior MOT methods that either ignore the crowd density and thus are prone to errors in crowded scenes, or rely on a suboptimal two-step process using heuristic density-aware point-tracks for matching targets. Our approach yields promising results on public benchmarks of various domains including people tracking, cell tracking, and fish tracking.

Assessing health-related quality of life in patients with inflammatory bowel disease in Zhejiang, China.

AIMS: The aim of this study was to assess health-related quality of life in patients with inflammatory bowel disease in Zhejiang, Mainland China. BACKGROUND: The incidence of inflammatory bowel disease in China is believed to be low but has been increasing in the past decade. The quality of life of Chinese patients with inflammatory bowel disease is unknown. DESIGN: A cross-sectional study. METHODS: The study was conducted in 92 patients with inflammatory bowel disease in Zhejiang, China, 52 with ulcerative colitis and 40 with Crohn's disease. Health-related quality of life was measured by the Chinese version of the Inflammatory Bowel Disease Questionnaire and Short Form-36, respectively. Disease activity was assessed by the Walmsley and Harvey-Bradshaw simple indices for ulcerative colitis and Crohn's disease, respectively. Demographic and clinical variables were also recorded. Short Form-36 data from the study sample were compared with a reference population of 1688 Chinese people residing in Hangzhou, Zhejiang, China. RESULTS: No significant health-related quality of life differences were found between patients with ulcerative colitis and Crohn's disease (p > 0.05). Pooled data showed that inflammatory bowel disease patients with active disease had significantly lower scores for all eight dimensions of Short Form-36 compared to those in remission (p < 0.01); those with active disease scored significantly lower than population norms in all dimensions of Short Form-36 except mental health (p < 0.05); whereas those in remission scored significantly lower than population norms in role physical (p < 0.01) and general health dimensions (p < 0.05). The regression analyses identified only disease activity index and employment status to explain variations in health-related quality of life (p < 0.01). CONCLUSIONS: Inflammatory bowel disease similarly impairs health-related quality of life in patients with both ulcerative colitis and Crohn's disease. RELEVANCE TO CLINICAL PRACTICE: The results suggest that any interventions that produce a stable clinical remission, whether medical or surgical, allowing patients to return to their usual work position can decrease the disease impact on their daily lives.

Molecular and clinical progress in follicular lymphoma lacking the t(14;18) translocation (Review).

Although the majority of patients with follicular lymphoma (FL) harbor the t(14;18)(q32;q21) IGH/BCL2 gene rearrangement that leads to the overexpression of BCL2 protein, approximately 20% of FL cases lack t(14;18)(q32;q21). It is considered that BCL2 overexpression underscores the development of the majority of cases of FL and their transformation to more aggressive lymphoma [known as transformed FL (tFL)]. However, FL cases lacking the t(14;18)(q32;q21) translocation exhibit symptoms analogous to their t(14;18)­positive counterparts. An important goal of recent research on FL has been to clarify the distinctions between the two different forms of FL. Numerous studies have shed light onto the genetic and molecular features of t(14;18)­negative FL and the related clinical manifestations. In this review, we summarize the current knowledge of t(14;18)­negative FL occurring in the lymph nodes with an emphasis on the underlying molecular and clinical features. In addition, novel treatment directions are discussed.