[The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms].

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

22q11.2 deletion syndrome complicated with pulmonary alveolar proteinosis in a child: a case report.

BACKGROUND: To analyze the clinical data and next generation sequencing (NGS) results from a child with 22q11.2 deletion syndrome (22q11DS) complicated with pulmonary alveolar proteinosis (PAP) who was admitted to the Department of Pediatrics of Fuyang People's Hospital and to present a review of the literature. CASE PRESENTATION: A 9-year-old male child, whose face had a small mandible and high-arched palate, but lacked a cleft palate, had repeated respiratory tract infections and bronchiectasis. Clinical examination, computer tomography, and electronic bronchoscopy were performed. Genetic testing via NGS was undertaken. PAP was confirmed by Periodic Acid Schiff staining of milky white alveolar lavage fluid isolated by electronic bronchoscopy. A deletion of approximately 2.46 Mbp on chromosome 22q11.2 was confirmed by NGS. During hospitalization, anti-infection, nebulization, alveolar lavage, and regular application of thymosin were administered to the patient. The condition of the patient stabilized following treatment. CONCLUSIONS: 22q11DS and PAP are both rare diseases, and the manifestation of 22q11DS combined with PAP has not been previously reported. The diagnosis and treatment of this case will be a reference for future clinical work.

[Establishment of Beijing National Medical School Faculty of Dentistry].

The Beijing National Medical School Faculty of Dentistry was established in 1943. This article reviewed the files preserved in Beijing Municipal Archices and presented the early background of the establishment including the approval process, formulation of teaching plans and design of the curriculums. These historical records provide us with thought-provoking insights into the evolution of the stomatological discipline and subsequent development of various sub-disciplines, as well as the educational ideals embedded.

[Research progress on the relationship between non-coding RNA and liver regeneration].

After partial hepatectomy (PH) or liver injury, hepatocytes in a proliferating quiescent state are activated and begin to expand to repair the damaged liver. In recent years, studies have recognized that non-coding RNA (ncRNA) represented by microRNA (miRNA) and long non-coding RNA (lncRNA) can participate in liver regeneration by regulating the proliferation, apoptosis, autophagy, and proliferation and migration of hepatic progenitor cells (HPCs). This article reviews the relationship between miRNA, lncRNA, and liver regeneration, with a view to provide a new therapeutic strategies for liver disease and liver regeneration.

Long noncoding RNA ZFPM2-AS1 regulates ITGB1 by miR-1226-3p to promote cell proliferation and invasion in hepatocellular carcinoma.

OBJECTIVE: Long noncoding RNA (lncRNA) is emerging as a vital regulator in various tumors. However, the biological function of ZFPM2-antisense RNA 1 (ZFPM2-AS1) in hepatocellular carcinoma (HCC) remains unclear. The present study aims to explore the function and mechanism of ZFPM2-AS1 in hepatocellular carcinoma progression. PATIENTS AND METHODS: The ZFPM2-AS1 expression in HCC cells and tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Effects of ZFPM2-AS1 on tumor cell proliferation and invasion were detected by CCK8 assay or EdU assay or matrigel migration assay and Western blot. The Luciferase reporter assay, RNA pulldown assay, qRT-PCR, and Western blot were performed to explore and confirm the interaction between ZFPM2-AS1 and miR-1226-3p and integrin ß1 (ITGB1). RESULTS: ZFPM2-AS1 was overexpressed in HCC tissues and cell lines. High levels of ZFPM2-AS1 were correlated with advanced TNM stage, distant metastasis and a poorer overall survival rate. ZFPM2-AS1 knockdown inhibited cell proliferation and invasion. ZFPM2-AS1 could directly bind to and negatively regulate miR-1226-3p expression. Moreover, ITGB1 was identified as a target gene of miR-1226-3p. ITGB1 was found to be directly negatively regulated by miR-1226-3p and indirectly upregulated by ZFPM2-AS1. Rescue assays demonstrated that ZFPM2-AS1 promotes HCC cell proliferation and invasion through modulating miR-1226/ITGB1 axis. CONCLUSIONS: ZFPM2-AS1 promotes cell proliferation and migration by regulating miR-1226-3p/ITGB1 axis in HCC.

Combinatory effect of mesenchymal stromal cells transplantation and quercetin after spinal cord injury in rat.

OBJECTIVE: To investigate the synergistic effects of quercetin (Qu) administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following spinal cord injury (SCI). MATERIALS AND METHODS: HUMSCs were isolated, cultured and certificated via flow cytometry. Sixty Sprague-Dawley (SD) female rats were used and SCI models were made. All rats were divided into five experimental groups: culture medium treated group (n=28); HUSMCs + quercetin-treated group (n = 28); HUMSCs treated group (n=28); quercetin-treated group (n = 28); sham group (n = 20). Basso, Beattie, and Bresnahan (BBB) were used to assess neurological function recovery. Axons at the injury epicenter of the injury were checked by immunohistochemical analysis. Cystic cavity was measured and rat cytokine Luminex custom 8-plex kits (for interleukin (IL)-4, IL-1ß, IL-6, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-ß1) were checked. RESULTS: The combination treatment with Qu and delayed transplantation of HUMSCs after rat SCI improved neurological functional recovery, increased axonal preservation, promoted macrophage polarization, decreased the size of the cystic cavity, reduced the proinflammatory cytokines, including IL-1ß and IL-6. Also, it increased anti-inflammatory cytokines, including IL-4, IL-10, and transforming growth factor (TGF)-ß1. CONCLUSIONS: We showed that HUMSCs transplantation in combination with Qu was a potential strategy for reducing secondary damage and promoting functional recovery following SCI.

Cardiovascular disease in rheumatoid arthritis: medications and risk factors in China.

This study aims to assess the risk factors of cardiovascular disease (CVD) and to determine the association of traditional and biologic disease-modifying anti-rheumatic drugs (DMARDs) with risk for CVD in Chinese rheumatoid arthritis (RA) patients. A cross-sectional cohort of 2013 RA patients from 21 hospitals around China was established. Medical history of CVD was documented. The patients' social background, clinical manifestations, comorbidities, and medications were also collected. Of the 2013 patients, 256 had CVD with an incidence of 12.7%. Compared with non-CVD controls, RA patients with CVD had a significantly advanced age, long-standing median disease duration, more often male and more deformity joints. Patients with CVD also had higher rates of smoking, rheumatoid nodules, interstitial lung disease, and anemia. The prevalence of comorbidities, including hypothyroidism, diabetes mellitus (DM), hypertension, and hyperlipidemia, was also significant higher in the CVD group. In contrast, patients treated with methotrexate, hydroxychloroquine (HCQ), and TNF blockers had lower incidence of CVD. The multivariate analysis showed that the use of HCQ was a protective factor of CVD, while hypertension, hyperlipidemia, and interstitial lung disease were independent risk factors of CVD. Our study shows that the independent risk factors of CVD include hypertension, hyperlipidemia, and interstitial lung disease. HCQ reduces the risk of CVD in patients with RA.

[Detection of peripheral follicular helper T cells in rheumatoid arthritis].

OBJECTIVE: To detect cell frequency and surface markers of peripheral CD4+CXCR5+ follicular helper T (Tfh) cells and analyze the correlation between CD4+CXCR5+Tfh cells and rheumatoid arthritis (RA) disease activity. METHODS: Forty RA patients meeting the American College of Rheumatology classification criteria for RA and twenty healthy controls (HC) were included. The peripheral blood mononuclear cells and sera were collected. The expressions of CD4+CXCR5+Tfh cells (CXCR5, C-X-C chemokine receptor type 5) and inducible T cell costimulator (ICOS), programmed death 1 positive (PD-1), interleukin-21 receptor (IL-21R) and CD40 ligand (CD40L) positive on CD4+CXCR5+Tfh cells were analyzed by flow cytometry. The transcript levels of B-cell lymphoma 6 (Bcl-6), as well as IL-21 and IL-21R, were measured by real-time polymerase chain reaction. Besides, serum IL-21 and CXCL13 concentrations were determined by enzyme-linked immunosorbent assay. The potential association between Tfh cells and RA disease activity was detected. RESULTS: The cell surface marker of CXCR5+ on CD4+ cells was significantly increasingly higher across the following groups versus HC: total RA patients (16.75±3.92 vs.7.49±1.84, P<0.001); RA patients with low disease activity or remission (16.62±3.43 vs. 7.49±1.84, P<0.001); RA patients with moderate disease activity (16.82±3.07 vs. 7.49±1.84, P<0.001) and RA patients with high disease activity (16.87±5.50 vs. 7.49±1.84, P<0.001). Besides, the percentages of ICOS+, PD-1+, IL-21R+ on CD4+CXCR5+Tfh cells in the RA patients were significantly higher than that of HC (ICOS+CD4+CXCR5+cells, 8.37±4.28 vs. 3.72±1.81, P<0.001; PD-1+CD4+CXCR5+cells, 1.57±1.10 vs. 0.24±0.30, P=0.035; IL-21R+CD4+CXCR5+ cells, 4.60 ±4.05 vs. 0.20±0.19, P=0.006). But the percentage of CD40L+ on CXCR5+CD4+Tfh cells in the RA patients was not significantly higher than that of HC (3.38±3.71 vs. 0.54±0.34, P=0.135). The IL-21R mRNA expression was elevated significantly (5.00±4.94 vs. 0.74±0.55, P<0.001) in the RA patients but not in Bcl-6 mRNA[4.54(3.33, 7.23) vs. 5.31(2.81, 7.44), P=0.329]or IL-21 mRAN[0.72(0.26, 3.45) vs. 0.56(0.27, 3.71), P=0.195]. Additionally, the serum interleukin-21 (IL-21) and CXCL13 levels in the RA patients were higher than in the healthy controls [IL-21, (200.49±154.56) ng/L vs. (8.21±5.95) ng/L, P<0.001; CXCL13, (93.72±49.72) ng/L vs. (43.09±1.28) ng/L, P<0.001] and were both positively correlated with RA disease activity indexes, including erythrocyte sedimentation rate, the disease activity score in 28 joints (ESR-based or CRP-based), clinical disease activity index, and simplified disease activity index. However, none of the Tfh cells, anti-citrullinated protein antibody or rheumatoid factor had any relationship with RA disease activity. CONCLUSION: Peripheral Tfh cells and their relevant cytokines are higher in RA patients than healthy controls, indicating Tfh cells may participate in the pathogenesis of RA, therefore, blocking the pathway of Tfh cells may be reasonable cellular targets for therapeutic intervention.

Funnel compression suture: a conservative procedure to control postpartum bleeding from the lower uterine segment.

Bleeding from the lower uterine segment (LUS) during caesarean section remains a life-threatening obstetric problem, particularly in women with placenta praevia or partial placenta accreta in the LUS. Various conservative measures for the surgical treatment of postpartum haemorrhage have been studied for decades. In this paper we describe a funnel compression suture to staunch intractable bleeding from LUS for placenta praevia accreta. The suture brings the anterior and posterior walls of the LUS together using absorbable thread and was successful in the overwhelming majority of women. It is an easy, safe and effective conservative surgical treatment to stop severe bleeding of the LUS.

Efficacy of chlortetracycline treatment on vulvar non-neoplastic epithelial disorders.

OBJECTIVE: To observe the effectiveness of chlortetracycline (aureomycin) treatment on vulval white lesions and to explore its possible pathogenesis. MATERIALS AND METHODS: From January 2001 to April 2011, 194 patients with vulvar non-neoplastic epithelial disorders were divided into three groups according to therapy regimens received, ie, chlortetracycline treatment group (72 cases), chlortetracycline + beclomethasone treatment group (66 cases), and beclomethasone treatment group (56 cases); their local changes of vulvar lesions were observed and efficacy of these treatment profiles was evaluated after one year. RESULTS: Effective rates of chlortetracycline group, chlortetracycline + clobetasol group and clobetasol groups were 86.1% (62/72), 87.9% (58/66), and 62.5% (35/56), respectively. There was a significant difference among these three groups (Hc = 10.7766,p = 0.0046), the curative rate of clobetasol group was markedly lower than that of the former two groups (p = 0.0072 and p = 0.0019), but was not statistical significant (p = 0.6077) when compared between the former groups. CONCLUSION: The occurrence of vulvar non-neoplastic epithelial disorders may be associated with chlamydia and mycoplasma infection, the chlortetracycline is an effective drug for this illness, the mechanism of which might be related to killing pathogens directly and inhibiting inflammatory mediators.

The use of targeted percutaneous laser disc decompression under the guidance of puncture-radiating pain leads to better short-term responses in lumbar disc herniation.

OBJECTIVE: Traditional percutaneous laser disc decompression (PLDD) eliminates nucleus pulposus in the center of lumbar discs. Targeted PLDD is an alternative technique that involves elimination and decompression of the target area located 5-8 mm in the front of the herniated disc. We aimed to compare the efficacy of targeted PLDD with traditional PLDD in the treatment of lumbar disc herniation and evaluate the usefulness of guidance by puncture-radiating pain on clinical outcomes of PLDD. PATIENTS AND METHODS: We treated 61 patients with lumbar disc herniation. Patients were stratified into control group, which included patients who underwent traditional PLDD, and study group in patients underwent targeted PLDD. Clinical outcomes and efficacies were evaluated at different time points using the visual analog scale (VAS) and modified MacNab criteria. RESULTS: Patients in the study group demonstrated significantly greater decreases in the VAS scores compared with those in control group. These differences were observed on Day 3, and 1 and 3 months after the treatment. Further, VAS scores were markedly lower in the patients whose treatment was guided by the puncture-radiating pain. Thus, at 1 month after the operation, 64.1% of those patients showed excellent or good outcomes based on MacNab criteria, which was almost twice the percentage seen in patients who did not experience the puncture-radiating pain (36.4%). CONCLUSIONS: Targeted PLDD is an effective, minimally invasive, and safe technique for lumbar disc herniation, and this technique achieves better short-term postsurgical outcomes than traditional PLDD. Puncture-radiating pain is an important prognostic indicator for better short-term responses to the treatment.

Alteration of T-cell subpopulations and lipid peroxidation in the blood of patients with vulvar non-neoplastic epithelial disorder.

OBJECTIVE: To determine the relationship between vulvar non-neoplastic epithelial disorder and thymus-dependent lymphyocyte levels and lipid peroxidation. MATERIALS AND METHODS: the authors measured the levels of CD3+, CD4+, CD8+, CD16+ T cell, and the concentration of superoxide dismutase (SOD) and malondialdehyde (MDA) in the blood of 62 patients with vulvar non-neoplastic epithelial disorder. A control group consisted of 30 normal women from the present hospitals. RESULTS: The level of CD4+/CD8+ T-lymphocytes and SOD in the blood of the patients with vulvar non-neoplastic epithelial disorder was significantly lower than that in control subjects, but the level of MDA was higher as compared with normal women. CONCLUSION: There is increased immune activation and lipid peroxidation in patients with vulvar non-neoplastic epithelial disorder, which could contribute to destruction of vulvar tissue.

Wood smoke exposure induces a pulmonary and systemic inflammatory response in firefighters.

Epidemiological studies report an association between exposure to biomass smoke and cardiopulmonary morbidity. The mechanisms for this association are unclear. The aim of the present study was to characterise the acute pulmonary and systemic inflammatory effects of exposure to forest fire smoke. Seasonal forest firefighters (n = 52) were recruited before and/or after a day of fire-fighting. Exposure was assessed by questionnaires and measurement of carbon monoxide levels (used to estimate respirable particulate matter exposure). The pulmonary response was assessed by questionnaires, spirometry and sputum induction. Peripheral blood cell counts and inflammatory cytokines were measured to define the systemic response. Estimated respirable particulate matter exposure was high (peak levels >2 mg x m(-3)) during fire-fighting activities. Respiratory symptoms were reported by 65% of the firefighters. The percentage sputum granulocytes increased significantly from 6.5 to 10.9% following fire-fighting shifts, with concurrent increases in circulating white blood cells (5.55x10(9) to 7.06x10(9) cells x L(-1)) and band cells (0.11x10(9) to 0.16x10(9) cells x L(-1)). Serum interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 levels significantly increased following fire-fighting. There were no changes in band cells, IL-6, and IL-8 following strenuous physical exertion without fire-fighting. There was a significant association between changes in sputum macrophages containing phagocytosed particles and circulating band cells. In conclusion, acute exposure to air pollution from forest fire smoke elicits inflammation within the lungs, as well as a systemic inflammatory response.

[Immunologic suppressor factors in sera of patients with ovarian cancer].

The suppressive activity of immunologic suppressor factors (ISF) in the sera of 34 patients with ovarian cancer was investigated by using the lymphocyte proliferation and inhibition test. It was found that the sera of the preoperative patients could significantly suppress PHA-induced lymphocyte response, and that the suppression was dose-dependent. When the sera were diluted to 1 : 4,000, the suppressive activity could still be demonstrated. We also observed the suppressive activities in the sera of patients with cervical cancer, endometrial cancer, gastric cancer and lung cancer, and compared them with ovarian cancer patients. The observation showed that the suppressive activity in the sera of preoperative ovarian cancer patients was higher than that in the sera of gastric cancer or lung cancer patients. These results suggested that ISF played an important role in the development of ovarian cancer.