Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

This study aimed to investigate the effect of microRNA-155 (miR-155) in chronic obstructive pulmonary disease (COPD) and cigarette smoke extract (CSE)-treated airway smooth muscle cells (ASMCs) by targeting phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) to regulate the PTEN/PI3K/Akt signaling pathway. The COPD mouse model was induced by lipopolysaccharide (LPS) combined with passive smoking. After modeling, miR-155 mimics and miR-155 inhibitor were used for intervention treatment. The pulmonary function of each group was detected by an EMKA detector. Hematoxylin-eosin (HE) staining was used to observe the pathological changes and scores of lung tissues. The expression of TNF-α, IL-6, and IL-1β in bronchial alveolar lavage fluid (BALF) was detected by ELISA. Primary ASMCs were isolated and cultured in adherent tissue culture. The proliferation activity was detected by CCK-8 and EdU assays. Transwell and wound healing assays were used to measure the migration of ASMCs. The targeting relationship between miR-155 and PIK3R1 was validated by a double luciferase reporter gene assay. The expression levels of miR-155 and PIK3R1 mRNA in lung tissues of mice in each group were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was used to detect the expression levels of Ki67, PNCA, PTEN, p-PI3K, PI3K, p85α, p-Akt, and Akt in lung tissues and ASMCs. The results showed that lung function was significantly reduced in the miR-155 mimic group, and the levels of PIK3R1 were significantly increased; while lung function in the miR-155 inhibitor group was significantly improved. The results of HE staining showed that there was obvious inflammatory cell infiltration in the miR-155 mimics group compared to that of the model group. Lung histopathological injury was significantly reduced in the miR-155 inhibitor group, accompanied by decreased expression of Ki67, PNCA, PI3K, p-Akt, increased PTEN and p85α protein levels, and reduced levels of TNF-α, IL-6, and IL-1β in BALF. The results of the double luciferase reporter gene assay showed that miRNA-155 could target bind to PIK3R1. Compared with those in the CSE+miR-155 NC group, the proliferation and migration of ASMCs were significantly increased in the CSE+miR-155 group. The proliferation and migration of ASMCs were significantly attenuated in the CSE+miR-155+pcDNA PIK3R1 group compared with those in the CSE+miR-155 group, accompanied by decreased expression of Ki67, PNCA, p-Akt and increased PTEN and p85α protein levels. These results suggest that miR-155 activates the PTEN/PI3K/Akt signaling pathway by targeting PIK3R1 to promote the occurrence and development of COPD, which provides new evidence for the use of miR-155 in the treatment of COPD.
Animals ; Mice ; Interleukin-6 ; Ki-67 Antigen ; MicroRNAs ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Pulmonary Disease, Chronic Obstructive ; Tumor Necrosis Factor-alpha

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

As a common soft tissue disease, the mechanism of tendinopathy has not been clarified and is lack of effective treatment method. Change of tissue fibrosis is the one of the main pathological features. Transforming growth factor beta 1 (TGF-β1), which is one of the important factor, participated in fibrosis. Inconsonant expressions of TGF-β1 could be found in tendinopathy. The studies are still controversial, but the vast majority of studies had showed that TGF-β1 was abnormal, and it is given priority to increase, which means that TGF-β1 plays an important role in the process of tendinopathy. In the process of tendon injuries and repairs, the time of TGF-β1 increasing is inconsistent. The time for TGF-β1 plays a significant role has not been determined. TGF-β1 has abnormal expressions in both tendinopathy and tendon repairs, which are two opposite processes. Thus, it may not be a one-way adjustment factor, but has a pleiotropic. Recent studies showed that TGF-β1 was considered as binding to receptor and transferring signal into the cell. Now there are three different receptors are found. The classical pathway of TGF-β1 in intracellular signal transduction is mainly through activation of Smad pathway. In the same time, there are also some non-classical pathways. TGF-β1 could break balance of extracellular matrix, which may be a reason to cause tendinopathy. But the regulations of TGF-β1 on the extracellular matrix are complex and diverse, further studies are required. Existing researches showed that the performance of treatments on tendinopathy is unsatisfied by blocking TGF-β1 downstream pathway. Therefore, it is a good way to study the upstream mechanism of produce TGF-β1. It may be an effective method to find new targets to inhibit the development of tendinopathy better by finding the original source of TGF-β1.
Fibrosis ; Humans ; Signal Transduction ; Tendinopathy ; Transforming Growth Factor beta1

Objective: To analyze the clinical characteristics of recurrent thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET) to probe the risk factors for recurrent thrombosis in patients with ET and PV. Methods: The clinical data of 104 ET and PV patients with thrombosis in Beijing Anzhen Hospital from February 2001 to November 2016 were retrospectively analyzed. Thrombosis reoccurred in 38 patients. Statistical analyses were performed by multivariate logistic regression for risk factors of recurrent thrombosis in ET and PV patients. Results: Recurrent thrombosis occurred in 36.5% of patients with ET/PV, the total incidence rate in ET and PV patients was 9.8% patient-years, 12.3% patient-years and 5.7% patient-years in ET and PV respectively. There were a total of 56 re-thrombotic events, and 42.1% of events occurred within 1 year after the first thrombosis. The arterial re-thrombosis was 97.4% (most of acute coronary syndrome, ACS), and venous events was 2.6%. The most common cases of re-thrombosis were ACS in ET patients (18 cases, 64.3%), and cerebral infarction in PV patients (7 cases, 70.0%). The number of PV patients with 2 times or more re-thrombotic events was significantly higher than that of ET patients (9 cases, 90.0% vs 7 cases, 25.0%). The proportion of the patients with WBC>12.5×10(9)/L or Hct>45%, and thrombosis history or splenomegaly and high risk thrombotic events were higher than those with a single thrombus (52.6% vs 31.8%; 50.0% vs 30.0%; 86.8% vs 13.6%; 84.2% vs 33.3%; 52.6% vs 15.2%; 94.7% vs 53.0%; P values were 0.036,0.046, <0.001, <0.001, <0.001 and <0.001, respectively). Logistic regression analysis showed that thrombosis history (OR=13.697, P=0.025), splenomegaly (OR=13.301, P=0.034) and high risk stratification of thrombotic events (OR=44.618, P=0.025) were independent risk factors for recurrent thrombotic events. Conclusions: ET and PV patients had a higher risk of re-thrombosis. The incidence of re-thrombosis in ET was higher than in PV, ACS was more common cases of re-thrombotic events; but PV patients were more susceptible to multiple re-thromboses than ET ones, also with more cerebral infarction. Previous thrombus history, splenomegaly and high risk stratification of thrombotic events were independent risk predictors for re-thrombosis of ET and PV patients.
Humans ; Polycythemia Vera ; Retrospective Studies ; Risk Factors ; Thrombocythemia, Essential ; Thrombosis

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
Bortezomib/therapeutic use* ; Chromosome Aberrations ; Humans ; Multiple Myeloma/drug therapy* ; Prognosis ; Retrospective Studies

OBJECTIVETo investigate the effect of propofol on cell invasion and expressions of aquaporin-3 (APQ-3) and matrix metalloproteinase-9 (MMP-9) in human lung adenocarcinoma cancer A549 cells.

METHODA549 cells were treated with propofol at the concentrations of 25, 50, and 100 µmol/L for 12 or 24 h. RT-PCR was used to detect the effect of propofol on AQP-3 mRNA level in A549 cells, and the effects of propofol treatments for 24 h on AQP-3 and MMP-9 protein expression and the invasive ability of A549 cells were assessed with Western blotting and Transwell assay, respectively.

RESULTSCompared with the control cells, the cells treated with 25, 50, and 100 µmol/L propofol showed a obvious inhibition of AQP-3 mRNA expression, with inhibition rates ranging from 0.19 to 0.65 in cells with a 12-h treatment and from 0.13 to 0.41 in cells treated for 24 h; 100 µmol/L propofol treatment for 24 h produced the strongest inhibitory effect (0.13∓0.035, P<0.05). AQP-3 protein expression in cells treated with 25, 50, and 100 µmol/L propofol for 24 h (0.91∓0.009, 0.60∓0.020, and 0.57∓0.006, respectively) and MMP-9 protein expression in cells treated with 50 and 100 µmol/L propofol for 24 h (0.65∓0.006 and 0.46∓0.021, respectively) were significantly lower than those in the control cells (P<0.05). Treatment with 25, 50, and 100 µmol/L propofol for 24 significantly lowered the number of invading cells (122.55∓17.20, 96.33∓5.82, and 74.33∓2.85, respectively) compared with the control group (199.33∓23.88, P<0.05).

CONCLUSIONTreatment with 50 and 100 µmol/L propofol inhibits cell invasion by down-regulating the expression of AQP-3 and MMP-9 in A549 cells.

OBJECTIVETo explore the effect of propofol on H19 expression, migration and invasion of human breast cancer MDA-MB-231 cells in vitro.

METHODSMDA-MB-231 cells were randomly divided into 5 groups for treatment with basal medium, DMSO, or propofol at concentrations of 25, 50, and 100 µmol/L. H19 expression of the treated cells was assessed with RT-PCR, and the changes of cell motility, migration and invasion were evaluated with wound-healing assay and Transwell assays.

RESULTSTreatment of the cells with 25, 50, and 100 µmol/L propofol for 24 h down-regulated H19 by 17.83%, 37.50% and 63.67% (P<0.05), and suppressed cell motility by 13.46%, 36.54% and 46.17% (P<0.05), cell migration by 27.93%, 57.90% and 76.51% (P<0.05), and cell invasion by 25.72%, 53.32% and 81.43% (P<0.05), respectively.

CONCLUSIONPropofol-induced cell migration and invasion suppression are partially mediated by down-regulating H19 in MDA-MB-231 cells in vitro.

OBJECTIVETo compare the effect of transumbilical single-site single-port with that of transumbilical single-site double-port laparoscopic varicocelectomy in the treatment of varicocele in adolescents.

METHODSWe randomly assigned 80 varicocele patients aged 10 - 16 years to two groups of equal number to receive transumbilical single-site single-port and single-site double-port laparoscopic varicocelectomy, respectively. We compared the operation time, postoperative hospital stay, incisional pain, complications and satisfaction with the abdominal cosmetic outcomes between the two groups.

RESULTSAll the operations were successfully performed. The double-port group showed a significantly higher score on the Visual Analogue Scale than the single-port group (4.8 +/- 1.4 vs 3.6 +/- 1.1, t = -4.986, P < 0.01), but there were no significant differences between the two groups in the operation time ([29.8 +/- 4.2] vs [31.2 +/- 4.6] min, t = 1.383, P = 0.171), postoperative hospital stay ([1.95 +/- 0.7] vs [1.82 +/- 0.8] d, t = -0.784, P = 0.436), complications (0 vs 0) and scores on the satisfaction with abdominal cosmetic outcomes (4.6 +/- 0.6 vs 4.8 +/- 0.5, t = 1.253, P = 0.214). No recurrence, umbilical hernia, hydrocele and orchiatrophy were found in the two groups of patients at 6 months after operation, and no visible scar was observed on the abdominal surface.

CONCLUSIONWith strict surgical indications, single-site single-port and single-site double-port laparoscopic varicocelectomies have similar clinical effects in the treatment of varicocele, which leave no scar on the abdominal surface. Single-site double-port laparoscopy needs no special instruments and therefore is worthier of wide clinical application.

Adolescent ; Child ; Humans ; Laparoscopy ; methods ; Length of Stay ; Male ; Operative Time ; Umbilicus ; surgery ; Varicocele ; surgery

This study is to investigate the effect of Vam3, a dimeric derivative of resveratrol, on SNP-induced apoptosis and its potential mechanism in rat articular chondrocytes. Isolated rat articular chondrocytes were treated with sodium nitroprusside (SNP), a NO donor, to induce apoptosis. Apoptosis percentage was evaluated by Annexin V-PI and nucleus fracture was examined by DAPI staining. Level of intracellular reactive oxygen species (ROS) was detected using 2, 7'-dichlorofluorescin diacetate (DCFH-DA) as a fluorescence probe by fluorescence microplate reader. The change in mitochondrial membrane potential was detected by TMRE staining. Expressions of SIRT1, acetylated p53 (ac-p53), cleaved caspase 9 and cleaved caspase 3 were determined by Western blotting. It showed that Vam3 up to 10 micromol x L(-1) could significantly reduce SNP-induced rat articular chondrocytes apoptosis (P < 0.01) and nucleus fracture, inhibit the increase of intracellular ROS level (P < 0.01) and reverse the decrease in mitochondrial membrane potential (P < 0.01). Simultaneously, Vam3 could upregulate the expression of SIRT1, deacetylate p53, and inhibit the cleavage of caspase 9 and caspase 3 (P < 0.01) of rat articular chondrocytes exposed to SNP. This study indicates Vam3 could protect rat articular chondrocytes against SNP-induced apoptosis, perhaps through the upregulation of SIRT1 and deacetylation of p53.
Animals ; Apoptosis ; drug effects ; Arabidopsis Proteins ; pharmacology ; Cartilage, Articular ; cytology ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cells, Cultured ; Chondrocytes ; cytology ; metabolism ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Nitric Oxide Donors ; antagonists & inhibitors ; pharmacology ; Nitroprusside ; pharmacology ; Qa-SNARE Proteins ; pharmacology ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Sirtuin 1 ; metabolism ; Tumor Suppressor Protein p53 ; metabolism