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AIM Pulmonary hypertension (PH) is a pathophysiological syndrome with functional abnormalities of the pulmonary artery and heart, eventually becoming life threatening to the patients. Autophagy-related gene 7 (ATG)-7 is involved in many cardiovascular diseases, but little is known about the specific role of ATG-7 in the development of PH. We aimed to examine the expression of ATG-7 in PH patients and PH mice, specifically investigate pulmonary physiological responses in a mouse model with conditional deletion of ATG-7 in smooth muscle cells (SMCs) and further clarify the mechanism of PH caused by ATG-7 deficiency. METHODS AND RESULTS SMC-ATG-7-/- mice underwent echocardiography and subsequent pulmonary arterial pressure (PAP) checks. The PAP was lower in wild-type (WT) mice (22.6 ± 2.0 mmHg) than knockout (KO) mice (34.0 ± 2.5 mmHg; p

Background Limited studies have reported the relationship between intestinal flora dysbiosis and clinical characteristics in polycystic ovary syndrome (PCOS). However, the structure and characteristics of gut microbiota in PCOS have not been fully elucidated. Objective To analyze the composition of the Intestinal flora population in normal-weight women with PCOS and insulin resistance(IR) compared to PCOS alone and healthy women. Methods A total of 14 PCOS patients with insulin resistant(PCOS-IR) and 12 PCOS alone (PCOS-NIR), and 10 age- and body mass index-matched healthy control women (HC). BMI: 18.5–23.9 kg/m2. The bacterial 16 S rDNA V3-V4 fragment was amplified and sequenced. Then, the sequencing data were analyzed for species annotation, community diversity, and inter-group differences, to explore gut microbial characteristics of the subjects and their correlation with clinical parameters. Results No significant difference in diversity was observed between PCOA and sample cluster analysis among the three groups (Beta-diversity) and Alpha-diversity. The relative abundance of Rothia, Ruminococcus, and Enterococcus was significantly higher in the PCOS-IR group than in the other two groups (P Prevotella was dramatically decreased (P Enterococcus was positively correlated with waist circumference, hip circumference, diastolic blood pressure, and insulin resistance index. Meanwhile, Rothia abundance is positively associated with waist circumference and free fatty acids. Conclusions The gut microbial composition of PCOS patients with insulin resistance is different from that of PCOS alone and healthy women. The difference is correlated with the clinical characteristics of PCOS, with regards to insulin resistance, abdominal obesity, free fatty acids, and other indicators. PCOS-IR patients have an increased abundance of Enterococcus which potentially the intestinal environment of the host by enriching the metabolic pathways related to insulin resistance, causing the occurrence and development of PCOS.

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder. Typically, it is characterized by hirsutism, hyperandrogenism, ovulatory dysfunction, menstrual disorders and infertility. To date, its pathogenesis remains unclear. However, insulin resistance (IR) is considered as the primary pathological basis for its reproductive dysfunction. On the other hand, a condition in which insulin is over-secreted is called hyperinsulinemia. IR/Hyperinsulinemia is associated with chronic inflammation, hormonal changes, follicular dysplasia, endometrial receptivity changes, and abortion or infertility. Additionally, it increases incidence of complications during pregnancy and has been associated with anxiety, depression, and other psychological disorders. Gut microbiota, the “second genome” acquired by the human body, can promote metabolism, immune response through interaction with the external environment. Gut microbiota dysbiosis can cause IR, which is closely linked to the occurrence of PCOS. This article reviewed recent findings on the roles of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome.

Background miR‐145 is closely related to vascular smooth muscle cells (VSMC) phenotype transformation; however, the regulatory mechanisms through which miR‐145 regulates the VSMC phenotype transformation under mechanical stretching are unclear. In this study, we evaluated the roles of miR‐145 in VSMCs subjected to mechanical stretching in aortic dissection (AD). Methods The expression of miR‐145 in the aortic vessel wall of model animals and patients with AD was analyzed by quantitative polymerase chain reaction. miR‐145‐related protein‐protein interaction networks and Wikipathways were used to analyze VSMC phenotypic transformation pathways regulated by miR‐145. We used gain‐ and loss‐of‐function studies to evaluate the effects of miR‐145 on VSMC differentiation under mechanical stretch induction and assessed whether Krüppel‐like factor 4 (KLF4) was regulated by miR‐145 in the aorta under mechanical stretch conditions. Results miR‐145 was abundantly expressed in the walls of the normal human aorta, but was significantly downregulated in animal models and the walls of patients with dissection. We found that contractile phenotype‐related proteins were downregulated in VSMCs subjected to mechanical stretching, whereas the expression of secreted phenotype‐related proteins increased. miR‐145 overexpression also downregulated contractile phenotype‐related proteins in VSMCs and suppressed upregulation of phenotype‐related proteins. Finally, under mechanical stretching, KLF4 expression was significantly increased in VSMCs, and overexpression of miR‐145 blocked this effect. Conclusion Our results confirmed that mechanical stretch‐induced phenotypic transformation of VSMCs to promote AD via upregulation of KLF4; this mechanism was regulated by miR‐145, which directly modulated KLF4 expression and VSMC differentiation., miR‐145 was abundantly expressed in the walls of the normal human aorta, but was significantly downregulated in animal models and the walls of patients with dissection. Contractile phenotype‐related proteins were downregulated in VSMCs subjected to mechanical stretching, whereas the expression of secreted phenotype‐related proteins increased. Mechanical stretch induced phenotypic transformation of VSMCs to promote AD via upregulation of KLF4. This mechanism was regulated by miR‐145, which directly modulated KLF4 expression and VSMC differentiation.

This study aimed to assess the clinical characteristics and T‐helper 1 (Th1)/Th2 profile of human rhinovirus (HRV) infection in children with bronchiolitis and pneumonia, compared with the respiratory syncytial virus (RSV). In September 2013 to August 2014, 335 nasopharyngeal aspirates from children below 14 with bronchiolitis and pneumonia were screened for HRV and 13 other respiratory viruses by PCR or reverse transcription PCR. Interferon (IFN)‐γ, interleukin (IL)‐2, IL‐4, IL‐6, IL‐10, and tumor necrosis factor (TNF)‐α were detected by multiplex enzyme‐linked immunosorbent assay. HRVs were found in 66 cases (19.7%), including 35 bronchiolitis and 31 pneumonia cases. Compared with the RSV alone group, children with pneumonia had more frequent wheezing episodes in HRV (P a = .001) and HRV + non‐RSV (P b = .002) groups, and fever in the HRV (P f = .004) and HRV + RSV (P g = .005) groups. Among patients with bronchiolitis, cases with HRV alone were more likely to present in winter than those with RSV alone (P i = .010) and HRV + non‐RSV (P j = .014), and less numerous in summer compared with HRV + non‐RSV (P h = .005). Children with HRV alone were more susceptible to have a history of eczema than RSV alone among bronchiolitis (P c, Highlight HRV is a major non‐RSV pathogen causing hospitalization in children with bronchiolitis and pneumonia and induces an imbalanced Th1/Th2 response in bronchiolitis. Compared with RSV infection, HRV bronchiolitis and pneumonia differ significantly regarding wheezing episodes, susceptibility to eczema, fever occurrence and seasonal prevalence.

The loss of function of melanocytes leads to vitiligo, which seriously affects the physical and mental health of the affected individuals. Presently, there is no effective long-term treatment for vitiligo. Therefore, it is imperative to develop a convenient and effective treatment for vitiligo. Regenerative medicine technology for direct reprogramming of skin cells into melanocytes seems to be a promising novel treatment of vitiligo. This involves the direct reprogramming of the patient's skin cells into functional melanocytes to help ameliorate the loss of melanocytes in patients with vitiligo. However, this method needs to be first tested on mice. Although direct reprogramming is widely used, there is no clear protocol for direct reprogramming into melanocytes. Moreover, the number of available transcription factors is overwhelming. Here, a concentrated lentivirus packaging system protocol is presented to produce transcription factors selected for reprogramming skin cells to melanocytes, including Sox10, Mitf, Pax3, Sox2, Sox9, and Snai2. Mouse embryonic fibroblasts (MEFs) were infected with the concentrated lentivirus for all these transcription factors for the direct reprogramming of the MEFs into induced melanocytes (iMels) in vitro. Furthermore, these transcription factors were screened, and the system was optimized for direct reprogramming to melanocytes. The expression of the characteristic markers of melanin in iMels at the gene or protein level was significantly increased. These results suggest that direct reprogramming of fibroblasts to melanocytes could be a successful new therapeutic strategy for vitiligo and confirm the mechanism of melanocyte development, which will provide the basis for further direct reprogramming of fibroblasts into melanocytes in vivo.

Edaravone can induce differentiation of bone marrow mesenchymal stem cells (BMSCs) into neuron-like cells and replace lost cells by transplanting neuron-like cells to repair spinal cord injury (SCI). In this study, BMSCs were derived from the bone marrow of male Wistar rats (4 weeks old) through density gradient centrifugation (1.073 g/mL), and the cell purity of BMSCs was up to 95%. The combined injection of basic fibroblast growth factor and edaravone was conducted to differentiate BMSCs into neuron-like cells. In this study, 120 male Wistar rats were used to establish the model of semitransverse SCI; on the seventh day, neuron-like cells were labeled by BrdU and then injected into the epicenter of the injury of rats. On the 14th day after cell transplantation, the biotin dextran amine (BDA) fluorescent agent was used to track the repair of nerve damage. At 7, 14, 21, and 30 days after SCI, the Basso, Beattie, and Bresnahan (BBB) locomotor scale method was used to measure the functional recovery of hind limbs in rats. Additionally, hematoxylin and eosin (H&E) staining, Nissl staining, immunohistochemistry, transmission electron microscopy (TEM), Western blotting, and Real-time quantitative reverse transcripion PCR (qRT-PCR) were used to observe the regeneration of nerve cells. In the edaravone+BMSC group, behavioral analysis of locomotor function showed that functional recovery was significantly enhanced after transplantation of the cells, BrdU-positive cells could be observed scattered in the injured area and extended to both the head and tail, and the BDA tracer shows that the edaravone+BMSC group emits more fluorescent signals. Additionally, H&E staining, Nissl staining, and immunohistochemistry revealed that the space of spinal cord tissue was attenuated and the neurons were increased. Western blotting and qRT-PCR showed that the expression levels of neuron-specific enolase (NSE), Nestin, and neurofilament 200 (NF) were increased, while the expression of glial fibrillary acidic protein (GFAP) was decreased. TEM showed that cytoplasmic edema was reduced, mitochondrial vacuoles were attenuated, and nuclear chromatin concentration was declined after transplantation of neuron-like cells. Moreover, with the extension of time of edaravone+BMSC transplantation, the structures of mitochondria and endoplasmic reticulum tended to be normal. In summary, the induced differentiation of BMSC transplantation can significantly promote the functional repair of SCI.

BackgroundLegionella pneumophila is responsible for hospital or community-acquired pneumonia in adults. Immunocompromised patients with Legionella pneumophila infection are associated with rapidly severe clinical course and high mortality rates. Legionella pneumophila infection is rare in children, especially combined with extrapulmonary manifestations. In this report, we describe 2 children of severe hospital-acquired pneumonia and septic shock resulting from Legionella pneumophila. Standardized metagenomics next-generation sequencing allowed early diagnosis. Appropriate antibiotic therapy and timely extracorporeal life support were effective in achieving complete recovery. This is the first report of children with septic shock related to Legionella pneumophila infections diagnosed by metagenomics next-generation sequencing and recovered successfully.Case presentationThere were 2 cases about septic shock resulting from Legionella pneumophila. One was a six-month girl with congenital biliary atresia who underwent liver transplantation. She was suspected for rejecting the liver and admitted to hospital. The other one was a five-year-old boy with Burkitt lymphoma who was in the end of early chemotherapy. They both presented with fever, cough or shortness of breath during hospitalization. And they were transferred to PICU because of worsening dyspnea and decreased blood pressure. Patients were diagnosed by severe sepsis with septic shock likely resulting from hospital-acquired pneumonia. Metagenomics next-generation sequencing indicated L. pneumophila in blood and sputum. Aggressive intravenous fluids resuscitation and vasopressors were initiated on arrival to PICU, and they were placed on mechanical ventilation and continuous renal replacement therapy. Intravenous antibiotic therapy followed by azithromycin. Finally, the patients recovered without any long-term sequelae.ConclusionsThough sepsis or sepsis shock caused by Legionella pneumophila is rare in children, it can occur at high-risk population. Metagenomics next-generation sequencing is useful for conforming hard-to-culture pathogens and severely ill patients. The report remind pediatric physicians that we should be aware that Legionella pneumophila can cause severe sepsis or sepsis shock, especially in immunocompromised children. It is significant to select appropriate samples and pathogen detection methods in the early stage of disease.

Background Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems with various clinical manifestations. Renal involvement is common, but intracardiac thrombus is rarely reported as a complication of antiphospholipid syndrome (APS, also known as anticardiolipin syndrome). Anticoagulant therapy is the first-line treatment, and surgery is performed in severe cases. We report a case to improve clinicians’ understanding of disease diagnosis. Case presentation An 8-year-old girl was admitted to our hospital because of left costal pain, hematuria and fever. She had obvious edema occult blood 3+, urinary protein 3.2 g/24 h, albumin 17.6 g/L, and total cholesterol 7.21 mmol/L, consistent with a diagnosis of nephrotic syndrome. We continued to track the etiology of nephrotic syndrome and performed a renal biopsy, showing dsDNA 1:10 positivity, low C3, low platelets and hemoglobin, anticardiolipin IgM 12 U/ml, anti-β2-glycoprotein I (β2GPI) 223 U/ml; renal pathology suggested lupus nephritis (LN), and the patient was ultimately diagnosed with SLE, secondary APS and LN. The patient was treated with hormones and immunosuppressants. Sixteen weeks later, her urinary protein was 1+, and the quantity of urine protein was less than 0.5 g/d. Echocardiography showed that the mass in the right atrium was thrombotic. Heparin anticoagulant therapy was effective. Conclusion SLE can involve multiple systems and various complications. Thrombus in the right atrium is a rare complication of APS. Early diagnosis and treatment are key to improving the prognosis of children.

Thrombopoietin (TPO) can improve liver regeneration and fibrosis. We report on a patient with liver cirrhosis who received treatment with TPO to improve liver function. An 82-year-old male had liver cirrhosis with ascites due to hepatitis C virus infection. The Child–Pugh classification was Child B. The patient received human recombinant TPO for 12 months. The platelet counts increased and were maintained at 60–80×10(9)/L. The liver function improved, the ascites resolved, and the liver volume increased. These results indicate that the novel treatment with recombinant human TPO (rhTPO) may be effective for improving liver function in patients with liver cirrhosis.

Objective Presently, interesting research related to induced pluripotent stem cells (iPSCs) is emerging. However, the development of new therapies and techniques for treatment of refractory diseases is still required in dermatology. We are exploring novel methods to provide stem cell therapy and elucidate research mechanisms underlying troublesome diseases by reprogramming iPSCs from the fibroblasts of keloid lesions from patients in vitro. Method Here, we identified the expression of fibroblastic genes in the fibroblast derived from diseased individuals. Corresponding iPSCs were then produced by transfecting patient fibroblasts with non-modified RNA cocktails, expressing OCT4, SOX2, KLF4, cMYC, NANOG, and LIN28 reprogramming factors. The pluripotency of these patient-derived iPSCs was identified by immunocytochemistry, real-time quantitative polymerase chain reaction, and teratoma formation in vivo in non-obese diabetic/severe combined immunodeficiency mice. Results All iPSCs derived from patients significantly expressed the pluripotent transcription factors and could be expanded in vitro. Furthermore, induction of terminal differentiation in long-term culture and the capability of forming embryonic bodies to differentiate into all 3 germ layers in vivo were confirmed in immune-deficient mice. Conclusion Fibroblasts from a keloid patient were successfully reprogrammed to iPSCs in vitro. This reprogramming may provide a basis for the production of individualized modified artificial skin to prevent rejections after xenogeneic skin transplantation and trauma through autologous skin transplantation. These cells can also offer a new platform for research on mechanisms underlying skin diseases and personal medical applications.

Objective: Photodynamic therapy (PDT) is an effective method of treating skin tumors such as Bowen disease. Dermabrasion surgery removes the visible carcinoma, and PDT diminishes suspected malignant lesions. Combining the two methods can treat and prevent the recurrence of carcinoma. In this study, we describe a case of highly differentiated squamous cell carcinoma (SCC) located within a psoriatic lesion on the leg of a patient. Methods: Skin dermabrasion combined with four applications of PDT was used to successfully treat SCC. Topical tazarotene and calcipotriol ointments were used to treat the psoriasis, significantly improving the symptoms. Results: The SCC in the left leg disappeared without recurrence for 4 years of follow-up. Conclusions: PDT combined with skin dermabrasion is an effective method to treat SCC lesions with unclear boundaries.

Infantile digital fibromatosis is a rare, benign fibrous tumor among infants usually limited to fingers and toes. Most cases present themselves with round eosinophilic inclusion bodies of different sizes, similar to erythrocyte in the parakarytoplasm. Although infantile digital fibromatosis had been observed with a tendency of spontaneous regression after a rapid phase of growth in some reports, the recurrence rate of early surgical intervention remains high. And the mechanism of recurrence is still unknown. Human papillomavirus (HPV), as a circular icosahedral double-stranded DNA virus, is famous for its remarkable significant correlation with cervical cancer. However, the reports about the possible relationship of recurrent infantile digital fibromatosis and HPV infection are rare and inconsistent. Here, we report a recurrent case of infantile digital fibromatosis after surgical resection. Pathological biopsy of the recurrent site not only identified the diagnosis of infantile digital fibromatosis again, but found the sign of HPV infection. Family history indicated that the patient's grandmother had a history of verruca plana. After complete resection of recurrence, the tumor recurred again and the case is still being followed up. The unique case may serve as a clue to the pathogenesis of the relationship between recurrent infantile digital fibromatosis and HPV infection.

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged < 1 year (P = 0.003), children without fever and wheezing (P = 0.015 and P = 0.000), days of illness < 14 days (P = 0.002), children with bronchiolitis (P = 0.012) and children with RSV single infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89: 589-597, 2017. (C) 2016 Wiley Periodicals, Inc.

Inducible nitric oxide synthase (NOS2) and endothelial nitric oxide synthase (NOS3) gene play important roles in the susceptibility to type 2 diabetes mellitus (T2DM). The present study aims to detect the potential association of NOS2 and NOS3 gene polymorphisms with the susceptibility toT2DM and diabetic nephropathy (DN) in the Chinese Han population. Four hundred and ninety T2DM patients and 485 healthy controls were enrolled in this case-control study. The genotypes of NOS2 and NOS3 gene polymorphisms were analyzed by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. Our data demonstrated that the NOS2 rs2779248 and NOS2 rs1137933 genetic polymorphisms were significantly associated with the increased susceptibility to T2DM in the heterozygote comparison, dominant model, and allele contrast; and NOS3 rs3918188 genetic polymorphism was significantly associated with the increased susceptibility to T2DM in the homozygote comparison and recessive model. The allele-C and genotype-TC of NOS2 rs2779248, allele-A and genotype-GA of NOS2 rs1137933 and genotype-AA of NOS3 rs3918188 genetic polymorphisms might be the risk factors for increasing the susceptibility to T2DM. And a significant haplotype effect of NOS2 rs10459953/C- rs1137933/G- rs2779248/T was found between T2DM cases and controls. Moreover, NOS3 rs1800783 polymorphism was significantly associated with the increased susceptibility to DN in the heterozygote comparison, recessive model and allele contrast. At last, a positive correlation of family history of diabetes with NOS3 rs11771443 polymorphism was found in DN. These preliminary findings indicate that the NOS2 rs2779248, NOS2 rs1137933, and NOS3 rs3918188 genetic polymorphisms are potentially related to the susceptibility to T2DM, and the rs1800783 polymorphism might be considered as genetic risk factors for diabetic nephropathy, and family history of diabetes was closely associated with rs11771443 polymorphism in DN, and the genetic variants might be used as molecular markers for evaluating the risk of T2DM and diabetic nephropathy. © 2016 IUBMB Life, 68(7):516-525, 2016.

Mycobacterium tuberculosis is very rarely found in erythema induratum of Bazin; recently, we found an unusual case with positive acid‐fast bacilli and polymerase chain reaction for detecting M. tuberculosis in both skin lesions of the extremities and the site of Mantoux test.

Administration of propofol at the time of reperfusion has shown to protect the heart from ischemia and reperfusion (I/R) injury. The aim of the present study was to investigate the molecular mechanism underling the cardioprotective effect of propofol against myocardial I/R injury (MIRI) in vivo and in vitro. Rat heart I/R injury was induced by ligation of the left anterior descending (LAD) artery for 30 min followed by 2-hr reperfusion. Propofol pretreatment (0.01 mg/g) was performed 10 min before reperfusion. In vitro MIRI was investigated in cultured cardiomyocytes H9C2 following hypoxia/reoxygenation (H/R) injuries. Propofol pretreatment in vitro was achieved in the medium supplemented with 25 μmol/L propofol before H/R injuries. Propofol pretreatment significantly increased miRNA-451 expression, decreased HMGB1 expression, reduced infarct size, and I/R-induced cardiomyocyte apoptosis in rat hearts undergoing I/R injuries. Knockdown of miRNA-451 48 hr before I/R injury was found to increase HMGB1 expression, infarct size, and I/R-induced cardiomyocyte apoptosis in rat hearts in the presence of propofol pretreatment. These in vivo findings were reproduced in vivo that knockdown of miRNA-451 48 hr before H/R injuries increased HMGB1 expression and H/R-induced apoptosis in cultured H9C2 supplemented with propofol. In addition, luciferase activity assays and gain-of-function studies found that propofol could decrease HMGB1, the target of miRNA-541. Taken together our findings provide a first demonstration that propofol-mediated cardioprotection against MIRI is dependent of microRNA-451/HMGB1. The study provides a novel target to prevent I/R injury during propofol anesthesia.

Background Hepatic percutaneous microwave ablation (MWA) is usually performed in patients under conscious sedation. Nonetheless, many patients reported pain during the procedure. The current study investigated the safety and effectiveness of analgesia given at personalized dosage during the MWA procedure. Methods A total of 100 patients with hepatocellular carcinomas (HCCs) were included in this study. These patients underwent CT-guided percutaneous MWA between February and October 2017. Patients were randomized into two groups: Experimental group (n = 50) and Control group (n = 50). Patients in the Control group were given 5 mg of morphine intravenously, followed by 10 mg of morphine injected subcutaneously 30 min before surgery. Patients in the Experimental group were given a personalized dosage of morphine during the procedure when the Visual Analogue Scale (VAS) was ≥4. Other clinical and treatment parameters were also analysed. Results A significantly less amount of morphine (p

To investigate the expression intensity and prognostic significance of TGF-β1 protein in non-small cell lung cancer (NSCLC), immunohistochemistry was carried out in 194 cases of NSCLC and 24 cases of normal lung tissues by SP methods. The PU (positive unit) value was used to assess the TGF-β1 protein expression in systematically selected fields under the microscope with Leica Q500MC image analysis. We found that the TGF-β1 PU value was nearly two-fold higher in NSCLC than in normal lung tissues (p=0.000), being associated with TNM stages (p=0.000) and lymph node metastases (p=0.000), but not to patient age, gender, smoking history, tumor differentiation, histological subtype and tumor location (P>0.05). Univariate analysis indicated that patients with high TGF-β1 protein expression and lymph node metastases demonstrated a poor prognosis (both p=0.000, ). Multivariate analysis showed that TGF-β1 protein expression (RR = 2.565, p=0.002) and lymph node metastases (RR=1.874, p= 0.030) were also independent prognostic factors. Thus, TGF-β1 protein expression may be correlated to oncogenesis and serve as an independent prognostic biomarker for NSCLC.

Cutaneous CD30+ lymphoproliferative disorders represent a spectrum of skin lymphatic reticular proliferative diseases, including lymphomatoid papulosis (LYP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL), and borderline lesions between them. Although they all express CD30 as a phenotypic marker and share overlapping immunophenotypic features, they differ in clinical manifestations, pathological features, treatment, and prognosis. LYP is a kind of benign disease characterized by recurrent papules and nodules, and may spontaneously regress. PC-ALCL presents with solitary tumor or local grouped nodules characterized by large T-cells and may completely or partially resolve in fewer than half of cases. We reported a case of patient with clinical manifestation and pathologic features consistent with LYP in its early stages, which later turned into PC-ALCL. This patient was treated with acitretin combined with NB-UVB and had an obvious response.

Du-Huo-Ji-Sheng-Tang (DHJST) is a traditional Chinese herbal medicine used to treat osteoarthritis. In the present study, the therapeutic effect of DHJST on cartilage degradation in a rabbit model of osteoarthritis was investigated. In the knee joints of rabbits, anterior cruciate ligament transection (ACLT) was performed to induce experimental osteoarthritis. At the end of the sixth week, 30 rabbits with ACLT were divided into six groups, control group, DHJST group and Osaminethacine (OSA) group, which were followed for another 4 weeks. The other three groups of rabbits with ACLT were untreated with DHJST or OSA, which were sacrificed after 6 weeks, and served as 6-week time point controls. Results indicated that at the end of the sixth week after surgery, there was a significantly histological degeneration in the control group compared with the normal group. In the control group, the mean score for histological degeneration were further increases at 10th week, and there was a significantly lower mean score for histological degeneration in the DHJST group compared with the control group. To research the potential mechanism, the expression level of VEGF and HIF-1αwere detected. The expression of VEGF mRNA and HIF-1αmRNA are low in normal group, while the activities increase gradually in the control group. However, compared to that of the same time point model group, activity of VEGF and HIF-1αdecreased significantly in DHJST group. In conclusion, DHJST exerts significant therapeutic effect on osteoarthritis rabbits, and mechanisms are associated with inhibition of VEGF and HIF-1αexpression.

BACKGROUND In China, patients with rheumatoid arthritis (RA) are often treated with traditional Chinese herbal medicine. There are certain advantages of traditional Chinese medicine therapy in treatment of RA. OBJECTIVE To assess the efficacy and adverse reaction of Shenshi Qianghuo Dihuang Decoction (SQDD), a compound traditional Chinese herbal medicine, in treatment of RA. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS This was a 24-week prospective, randomized, controlled trial. Ninety RA patients meeting inclusion criteria from Shanghai Municipal Hospital of Traditional Chinese Medicine were randomly assigned to receive SQDD or methotrexate (MTX) with 45 cases in each group. The patients in SQDD group were orally administered with SQDD twice daily, and the patients in MTX control group were treated by oral administration of 15 mg MTX once a week. All the RA patients were treated for 24 weeks. MAIN OUTCOME MEASURES The primary outcome was the number of patients achieving the American College of Rheumatology 20% response. Clinical and laboratory parameters including tender joint count and swollen joint count, patient's global assessment and physician's global assessment (using a 0-10 cm visual analogue scale), duration of morning stiffness, plasma C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) and value of anti-cyclic citrullinated peptide (CCP) antibody were assessed. RESULTS After 24-week treatment, the response rates in SQDD group and MTX group were 62.53% (24/41) and 67.5% (28/40) respectively, and there was no statistical difference between the two groups (P>0.05). The patient's global assessment and physician's global assessment, morning stiffness, grip strength, tender joint count, swollen joint count and the levels of ESR, CRP and anti-CCP antibody in SQDD and MTX groups were improved significantly as compared with those before treatment, and there were no significant differences between the two groups. The efficacy of MTX in improving rest pain and joint tenderness was better than that of SQDD (P

Background Genetic factors seem to play a significant role in the susceptibility to systemic lupus erythematosus (SLE). Some researchers have described amino acid polymorphisms within the interleukin-4 receptor (IL-4R) [isoleucine50valine (Ile50Val), arginine576glutamine (Arg576Gln), etc.], the IL-10R (G241A and G520A), and the interferon-γ receptor (IFN-γR) [valine14methionine (Val14Met) and glutamine64arginine (Gln64Arg)]. Methods The Ile50Val genotypes were examined by the reverse transcription-polymerase chain reaction-single-strand conformation polymorphism (RT-PCR-SSCP) method and DNA sequencing. The RT-PCR-restriction fragment length polymorphism (RT-PCR-RFLP) method was used to detect the Arg576Gln, G241A, G520A, Val14Met, and Gln64Arg genotypes. Results There were significant differences in the genotype frequencies of Ile50/Ile50, G520/G520, and G520/A520 between the SLE group and healthy control group. There was a positive correlation between the IL-4R Ile50/Ile50 genotype and the susceptibility to SLE (P = 0.022). This was also found for the IL-10R G520/G520 (P = 0.004) and G520/A520 (P = 0.055) genotypes. The risk of SLE susceptibility was increased in individuals with the genotype combinations Ile50/Ile50 and Gln576/Arg576 (P = 0.056) and G241/G241 and G520/G520 (P = 0.004). The IFN-γR2 Arg64/Arg64 genotype decreased the risk of SLE (P = 0.047). A decreased risk of development of SLE was detected in individuals with the genotype combination IFN-γR2 Arg64/Arg64 and IFN-γR1 Val14/Val14 (P = 0.004). Conclusions The IL-4R Ile50/Ile50 and IL-10R2 G520/G520 and G520/A520 genotypes were shown to determine the susceptibility to SLE in a Chinese population, as were the combinations Ile50/Ile50 and Gln576/Arg576, and G241/G241 and G520/G520.

Osteoporosis is an important health problem in the world. Alpha2-HS glycoprotein (AHSG) is involved in bone formation and metabolism and has been considered as an important candidate gene for osteoporosis. In this study, we simultaneously tested linkage and/or association of the AHSG gene with the variation of bone mineral density (BMD), an important risk factor for osteoporosis. A sample of 1,260 subjects from 401 Chinese nuclear families (including both parents and their daughters) were studied. The daughters' ages ranged from 20 to 45 years. All the subjects were genotyped by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) at polymorphic Sac I site inside the exon 7 of the AHSG gene. This polymorphism involves a nucleotide substitution of C to G at the middle nucleotide of the codon at amino acid position 238, resulting in the replacement of threonine (ACC) with serine (AGC). BMD was measured at the lumbar spine and hip region by dual-energy X-ray absorptiometry (DXA). Using the QTDT (quantitative trait transmission disequilibrium test), we found no significant results for association or linkage between the AHSG gene and BMD variation at the spine or hip. Our data provided no evidence to support the AHSG gene as a quantitative trait locus (QTL) for the BMD variation in a Chinese population.

The thalamus plays a key role in filtering or gating information and has extensive interconnectivity with other brain regions. Recent studies provide evidence of thalamus abnormality in schizophrenia, but the resting functional networks of the thalamus in schizophrenia is still unclear. We characterize the thalamic resting-state networks (RSNs) in 72 patients with schizophrenia and 73 healthy controls, using a standard seed-based whole-brain correlation. In comparison with controls, patients exhibited enhance thalamic connectivity with bilateral precentral gyrus, dorsal medial frontal gyrus, middle occipital gyrus, and lingual gyrus. Reduced thalamic connectivity in schizophrenia was found in bilateral superior frontal gyrus, anterior cingualte cortex, inferior parietal lobe, and cerebellum. Our findings question the "disconnectivity model" of schizophrenia by showing the over-connected thalamic network during resting state in schizophrenia and highlight the thalamus as a key hub in the schizophrenic network abnormality.

The effect of high frequency oscillatory ventilation (HFOV) at early stage on hemodynamic parameters, extravascular lung water (EVLW), lung capillary permeability, CC16 and sICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome (ARDS) was explored. Central vein pressure (CVP) and pulse indicator continuous cardiac output (PiCCO) were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp) models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index (EVLWI), EVLW/intratroracic blood volume (ITBV) and pulmonary vascular permeability index (PVPI) were measured before and after modeling (T0 and T1), and T2 (1 h), T3 (2 h), T4 (3 h) and T5 (4 h) after HFOV. CC16 and sICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group (P

The PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is highly expressed in many types of tumors. However, its role in lung adenocarcinoma remains elusive. The aims of this study were to investigate the correlation between PBK/TOPK and mutant p53 in lung adenocarcinoma and to evaluate the effect of PBK/TOPK on cell proliferation and viability. Expression of PBK/TOPK and mutant p53 was detected in 127 cases of lung adenocarcinoma and was examined in the A549, GLC-82, and H358 lung adenocarcinoma cell lines by immunohistochemistry staining and Western blot assay. When PBK/TOPK expression was down-regulated by TOPK-specific siRNA in the A549 and GLC-82 lines, the effects of PBK/TOPK on cell proliferation, viability, and mutant p53 expression were evaluated. Expression of PBK/TOPK correlated positively with mutant p53 in both tumor tissues and cell lines. Kaplan-Meier survival analysis demonstrated that PBK/TOPK, mutant p53, lymph node metastasis, distant metastasis, high TNM stage, and poor tumor differentiation were associated with a poor prognosis. Cox multivariate analysis showed that PBK/TOPK, mutant p53, lymph node metastasis, and distant metastasis could each serve as an independent prognostic factor. After down-regulation of PBK/TOPK in the A549 and GLC-82 cell lines, mutant p53 expression was decreased, and cell proliferation and viability were significantly inhibited. Therefore, our results suggest that PBK/TOPK correlates with mutant p53 and affects cell proliferation and viability as well as prognosis in lung adenocarcinoma.

Aims The aim of this study was to evaluate the prevalence of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) expression, and explore the prognostic significance of PBK/TOPK expression alone and in combination with Ki67 and p53 expression in non-small-cell lung cancer (NSCLC). Methods and results We detected PBK/TOPK expression in 30 samples of normal lung tissue, 32 lymph node metastases and 279 primary non-small-cell lung cancers by immunohistochemistry, and analysed the correlation of PBK/TOPK expression with Ki67 and p53 expression in primary tumour tissues. The results showed that PBK/TOPK expression was higher in lymph node metastases (75%) than in primary tumours (44.8%) and normal lung tissues (0%). PBK/TOPK expression was associated with histological type, lymph node metastasis, and TNM stage, and was positively correlated with Ki67 and p53 expression in NSCLC. Univariate and multivariate survival analyses showed that PBK/TOPK expression was significantly associated with an unfavourable prognosis in NSCLC. The prognosis of patients with tumours positive for both PBK/TOPK expression and Ki67 or p53 expression was also significantly unfavourable. Conclusions PBK/TOPK expression is positively correlated with Ki67 and p53 expression, and can be used as an independent prognostic factor in NSCLC.

AIM: To explore the characteristics of multi-slice computed tomography (CT) manifestations of hepatic epithelioid angiomyolipoma (HEA), improve the rate of accurate diagnosis, and reduce the misdiagnostic rate. METHODS: The multi-slice CT manifestations in five patients who were diagnosed with HEA definitely by postoperative pathological examination were analysed retrospectively. Three female patients and two male patients were included. Before operation, four patients received plain CT scanning and dynamic enhancement scanning, and the other patient only received enhancement scanning, with immunohistochemical analysis conducted after postoperative pathological examination. Four patients were misdiagnosed by CT, including three patients misdiagnosed with hepatic cell carcinoma and one patient with focal nodular hyperplasia. RESULTS: Upper abdominal multi-slice spiral CT scanning and three-stage enhancement scanning were conducted in five patients with HEA before operation. HEA had certain characteristic CT manifestations: low density masses, a few relatively high-density masses or fat-density masses diffusely shown in foci, clear boundary, round or oval and large focus, and tumour size ranging from 3.1 cm × 2.5 cm to 7.0 cm × 5.2 cm. During enhancement scanning, the foci were significantly enhanced uniformly or non-uniformly during the arterial phase, while during the venous and equilibrium phases, the foci were enhanced continuously or showed obvious low-density masses. Obviously enhanced and widened vessels could be found adjacent to foci or in the central area of foci during the arterial phase. CONCLUSION: CT manifestations of HEA have certain characteristics. Primary diagnosis can be obtained by combining CT findings with clinical data, but pathological examination is still needed for a definite diagnosis.

This study was designed to investigate the association of HAb18G/CD147 expression and localization with clinicopathological parameters and prognosis in NSCLC. Two hundred and eight (208) specimens of surgically resected NSCLC were stained by immunohistochemistry utilizing mouse anti-human HAb18G/CD147 monoclonal antibody. High levels of HAb18G/CD147 expression were associated with male gender, smoking history, tumor position, distant metastasis status, and clinical stage (p

Although primary and metastatic brain tumors can cause intracranial hemorrhage, thalamic hemorrhage as the first presentation of an anaplastic astrocytoma has not been reported. We report a 47-year-old man who first presented with hypertensive hemorrhagic stroke. He improved with aggressive blood pressure control and recovered with minimal residual deficit within 10 days. This led to the initial misdiagnosis of uncontrolled hypertension as the cause of the stroke. He deteriorated rapidly 4 months later. A biopsy revealed an anaplastic astrocytoma. Misdiagnosis of tumor as stroke can occur in patients with vascular risk factors who do not have a previous history of neoplasia. Our case report is to heighten the awareness of the incidence of tumor apoplexy masquerading as stroke.

Prostate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model. Prostate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR. Over 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen. ARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity

To investigate the expressions of chemokine receptors and interleukin (IL) receptors on the peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients and their correlations with clinical features as well as SLE disease activity index (SLEDAI).The mRNA expressions of chemokine receptors and IL receptors on PBMCs of 93 SLE patients and 30 healthy controls were detected by reverse transcription-polymerase chain reaction, including CCR2, CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCRS, CX3CR1, XCR1, IL-4R, and IL-10R. The clinical features of SLE patients were recorded. The correlations of chemokine receptors and IL receptors mRNA expressions with clinical features as well as SLEDAI were assayed using linear regression analysis.The level of CCR5 mRNA in SLE patients (including active and inactive SLE) was significantly higher than that in healthy controls (P0.05), and there was no significant difference between active and inactive patients in this respect (P0.05). CX3CR1 mRNA expression significantly increased from healthy control to inactive SLE to active SLE in sequence. The others (except for CCR8, CXCR3, and IL-10R) in active SLE patients were significantly higher than those in both inactive SLE patients and healthy controls (all P0.05). There were positive correlations between SLEDAI and CCR2 (r = 0.424, t = 4.313, P0.001), CCR3 (r = 0.518, t = 5.410, P0.001), CCR4 (r = 0.376, t = 3.851, P0.001), CCR6 (r = 0.457, t = 4.513, P0.001), CXCR5 (r = 0.455, t = 4.629, P0.001), CX3CR1 (r = 0.445, t = 4.523, P0.001), as well as XCR1 (r = 0.540, t = 5.445, P0.001). And CCR5 mRNA expression level was positively correlated with IL-4R mRNA (r = 0.313, t = 2.353, P0.05). The patients with myositis and cutaneous vasculitis simultaneously showed lower levels of CCR5 and CX3CR1, and CCR5 expression was negatively correlated with the scores of SLEDAI in SLE cases accompanied by photosensitivity (r = 0.426, t = -2.155, P0.05).Increased expressions of CCR5 and CX3CR1 on PBMCs may be indicators in clinical survey for SLE.

Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.

AIM: To evaluate the application value of multi-slice spiral computed tomography (MSCT) for imaging determination of metastatic lymph nodes of gastric cancer and to explore reasonable diagnostic criteria. METHODS: Sixty patients with gastric cancer underwent 64 MSCT scans before operation. Gastric cancer samples and perigastric lymph nodes were obtained after operation, formalin fixation and haematoxylin-eosin staining. The metastatic conditions of gastric cancer and perigastric lymph nodes were determined under a light microscope. A total of 605 lymph nodes were grouped and assessed according to distribution, size, shape and degree of lymph node enhancement. Then, the findings were compared with the postoperative pathological results. RESULTS: Among 605 lymph nodes, 358 were confirmed as metastatic, accounting for 59.2%. A total of 535 lymph nodes were detected in original axis images combined with multiplanar reconstruction images of MSCT. The metastatic lymph nodes had specific signs in computed tomography. This study showed that the long diameter of lymph nodes ≥ 8 mm indicated metastasis; the sensitivity and specificity were 79.6% and 78.8%, respectively. The difference of the mean value of lymph node enhancement density ≥ 80 Hu indicated metastasis; the sensitivity and specificity were 81.6% and 75.6%, respectively. The ratio of short diameter to long diameter of lymph nodes ≥ 0.7 indicated metastasis; the sensitivity and specificity were 85.6% and 71.8%, respectively. CONCLUSION: MSCT is a non-invasive and reliable method for preoperative examination of gastric cancer. Sensitivity and specificity for prediction of lymph node metastasis are high.