AIM: To investigate the effect of epidermal growth factor receptor (EGFR) inhibitor erlotinib on kidney injury in diabetic nephropathy (DN) rat and the underlying mechanism.METHODS: The rat model of DN was induced by intraperitoneal injection of streptozotocin (STZ) at dose of 55 mg/kg.One week after STZ injection, the rats with blood glucose level exceeding 16.7 mmol/L were identified as diabetic.Diabetic rats were randomly divided into 2 groups: STZ group and STZ+erlotinib group.In addition, the normal rats were used as control group.The rats in STZ+erlotinib group were treated with erlotinib at 100 mg·kg-1·d-1 for 4 weeks(5th~8th week).The fasting blood glucose (FBG), serum creatinine (SCr) and 24 h urine protein were measured.The pathological changes of the kidney were observed by HE staining and Masson staining.The protein levels of EGFR, p-EGFR, transforming growth factor β1 (TGFβ1), Smad2/3, p-Smad2/3, collagen Ⅳ (ColⅣ) and fibronectin in the kidney tissues were determined by Western blot.The reactive oxygen species (ROS) level and malondialdehyde (MDA) content in the renal tissues were futher analyzed.RESULTS: Compared with control group, the levels of FBG, 24 h urine protein and Scr were significantly increased in STZ group (P<0.01).Compared with STZ group, the levels of FBG, 24 h urine protein and SCr in STZ+erlotinib group were markedly decreased (P<0.05).In additon, the glomerular structure was restored to normal, the proliferative degree of mesangial cells markedly attenuated, and the epithelial cells were in alignment in STZ+erlotinib group.Moreover, erlotinib significantly inhibited the protein levels of p-EGFR, TGFβ1, p-Smad2/3, ColⅣ and fibronectin in the kidney tissues of STZ rats.In addition, erlotinib also significantly inhibited the levels of ROS and MDA in the kidney tissues of STZ rats.CONCLUSION: Erlotinib ameliorates STZ-induced diabetic nephropathy possibly through inhibiting the activation of EGFR/TGFβ1-Smad2/3 signaling pathway in association with suppression of fibrosis and oxidative stress.

italic>Mycobacterium tuberculosis, responsible for tuberculosis (TB), remains a major health problem worldwide and is one of the infectious diseases causing increased morbidity and mortality worldwide. Biotin, namely vitamin H, is an important cofactor necessary for fatty acid biosynthesis, gluconeogenesis and amino acid metabolism in organisms including Mycobacterium tuberculosis. Due to its inability to ingestion biotin from outside, Mycobacterium tuberculosis can only obtain biotin through biotin biosynthesis. Different from the classical BioC-BioH, BioI-BioW and non-classical BioZ pathways, Mycobacterium tuberculosis synthesized biotin by "BioC-BioH(2)" pathway in the early stage. This review focuses on the unique biotin synthesis pathway of Mycobacterium tuberculosis and its key genes, especially the response of this pathway and biotin-dependent carboxylase to tuberculosis first-and second-line drugs, as well as inhibitors and natural products targeting biotin synthesis.

Objective To explore the clinical effects of aortic valvuloplasty in treatment of ventricular septal defect(VSD)with moderate or severe aortic valve insufficiency(AI)in children.Methods Thirteen children less than 14 years old underwent open heart surgery as well as aortic valvuloplasty for VSD with moderate or severe AI.There were 9 cases of subpulmonary VSD,perimenbranous VSD in 4 cases.AI was mo-derate in 4 cases,severe in 9 cases.Results There was no hospital death.Post-operative echocardiogram and X-ray revealed that both cardiothoracic ratio and left ventricular end diastolic diameter decreased markedly(P

Enterohemorrhagic Escherichia coli ; Escherichia coli Infections ; epidemiology ; Germany ; epidemiology ; Humans

LncRNAH19 has been implicated as having both oncogenic and tumor suppression properties in cancer. LncRNAH19 transcripts also serve as a precursor for miR-675. However, it is unknown whether LncRNAH19 and miR-675 are involved in the migration and invasion of hepatocellular carcinoma (HCC) cells. The purpose of this study was to investigate the effect and mechanism of LncRNAH19 and miR-675 on migration and invasion of HCC cells. The migration and invasion of HCC cells were measured by Transwell migration and invasion assays after transfection of HCC cells with miR-675 inhibitors and LncRNAH19siRNA. The levels of LncRNAH19 and miR-675 were detected by quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR), and the protein expression of AKT, GSK-3β and Cdc25A by Western blotting analysis. The expression levels of LncRNAH19 and miR-675 were higher in MHCC-97H cells than in L02, Huh-7 and HepG2 cells. Transwell migration assay revealed that the miR-675 inhibitor and LncRNAH19siRNA could significantly increase the migration of HCC cells (P<0.01) as compared with the control group. Transwell invasion assay demonstrated that the miR-675 inhibitor and LncRNAH19siRNA could significantly increase the invasion of HCC cells (P<0.01) as compared with the control group. Western blotting analysis showed that the expression levels of AKT and Cdc25A were significantly increased (P<0.05), and the expression level of GSK-3β was significantly decreased (P<0.05) after treatment with miR-675 inhibitors and LncRNAH19siRNA as compared with the control group. These findings suggested that inhibition of LncRNAH19 and miR-675 expression can promote migration and invasion of HCC cells via AKT/GSK-3β/Cdc25A signaling pathway.

Objective To investigate the therapeutic effect of the Hubei Wingnut ( Malus hapehensis ) leaf decoction (MHD) against conjunctivitis infected with human simplex virus type I (HSV-1). Methods Malus hupehcnsis decoction was used as the active treatment and ribavirin ( RBV) eye drop was used as the positive control. Both of the Vero cells and rabbit eye conjunctiva were infected with HSV-1. The effect and mechanism of the MHD on viral replication was determined by observing the cytopathic effect ( CPE) . The efficacy of MHD at different doses on the rabbit viral conjunctivitis was examined by pathological changes of eye conjunctiva tissues. Results MHD did not inhibit the proliferation of HSV-1 in vitro. The inflammatory reactions of rabbit viral conjunctivitis caused by HSV-1 were obviously attenuated or disappeared after treatment with MHD at 6 kg·L-1 and 3 kg·L-1 for 7 consecutive days,compared with the negative control of 0. 9% NaCl. The curative rate of MHD at the middle and high doses was 83. 3% and 100. 0%, respectively. Conclusion MHD has the potential for treating eye conjunctivitis caused by HSV-1 by relieving inflammation.

Objective To define individualized internal target volume (ITV) for hepatocellular car-cinoma using four-dimensional (4D) CT, and to compare the differences in target volume definition and dose distribution among 3D, 4D and respiratory-gated plans. Methods 4DCT scanning was obtained for 12 pa-tients with hepatoceUular. Gross tumor volume (GTV), clnical target volume (CTV) and normal tissues were contoured on all 10 respiratory phases of 4DCT images. The 3D, 4D and gated treatment plans were prepared for each patient using three different planning target volumes (PTVs): 1) PTV3D was derived from a single CTV plus conventional margins;2) PTV4D was derived from ITV4D, which encompassed all 10 CTVs plus setup margins (SMs);3) PTV_(Gating) was derived from ITV_(Gating), which encompassed 3 CTVs within ga-ting-window at end-expiration plus SMs. The PTV volume and dose distribution were compared among differ-ent plans. Results The PTV3D was the largest in all 12 patients, but still missed partial target volume in 5 patients when comparing with PTV4D. Both the 4D plans and the gated plans spared more normal tissues than the 3D plans, especially the hver. Without increasing normal tissue dose, the 4D plans allowed for increas-ing the calculated dose from (50.8±2.0) Gy (3D plans) to (54.7±3.3) Gy, and the gated plans could further increase the dose to (58.0±3.9) Gy. Conclusions The 4DCT-based plans can ensure optimal tar-get coverage with less irradiation of normal tissues and allow dose escalation when compared with 3D plans.Respiratory gated radiotherapy can further reduce the target volumes to spare more surrounding tissues, espe-cially for patients with large extent of respiratory mobility.

Objective To investigate the MR features of pituitary abscess.Methods The MR features of 14 cases of pituitary abscess proved by surgical pathology and clinical treatments were analyzed retrospectively.Results Pre-contrast MR showed hypointense heterogeneous intensity on T_1 WI in 12 cases and iso-hyperintense on T_1 WI in 2 cases,hyperintense on T_2 WI in all cases.Post-gadolinium MR showed the ring-like enhancement around the uneven edge of abscess and the surrounding enhanced meninges connecting to the focus.The normal pituitary could not be identified in all 14 cases.The MR specific findings include the fluid-fluid level,nodule on the edge and the enhanced patchy shadow.Conclusions The pituitary abscess has specific findings on MR examination,which can be used to combine with clinical symptoms to achieve the diagnosis before operation,so that the cases could be treated with antibiotic without operation.

To study whether commercial traditional Chinese medicinal preparations Injection Paederiae (IP) or Injection Stauntonia (IS) has anti-nociceptive and/or anti-inflammatory effects, we used two persistent pain models (bee venom and formalin test) to evaluate the systemic effects of IP or IS on the chemical tissue injury-induced persistent spontaneous pain-related responses (PSPR), primary thermal/mechanical hyperalgesia and inflammation in conscious rats. Injection of bee venom (BV, 0.1 mg, 50 microl) into the plantar surface of one hind paw resulted in not only a 1-h monophasic PSPR such as flinching reflex in the injected paw and a subsequent period of 3-4 days primary heat and mechanical hyperalgesia, but also a marked sign of inflammation, including redness and swelling of the plantar surface in the injected paw. Intraplantar injection of formalin produced two phases of PSPR as reported previously. Systemic pre-treatment with three doses of IP (0.32, 1.6 and 9.0 ml/kg, 500%) or IS (0.32, 1.6 and 9.0 ml/kg, 250%) produced a dose-dependent suppression of the BV- or formalin-induced flinching reflex of 1 h time course as compared with the saline control group. Post-treatment with IP or IS 5 min after BV injection also produced a significant suppression of the flinching reflex in both BV test and formalin test respectively, as compared with the control group. However, neither pre- nor post-treatment with IP or IS produced any significantly suppressive effect on the BV-induced primary heat and mechanical hyperalgesia and inflammation. The analgesia produced by IP or IS was not mediated by the endogenous opioid receptors since naloxone, a non-selective opioid receptor antagonist, had no reversal effect on the IP and IS-produced analgesia in the BV-induced PSPR. Our present results suggest that IP or IS might prevent and relieve clinical persistent spontaneous pain, but without any anti-nociceptive and anti-inflammatory effects on the primary heat hyperalgesia, mechanical hyperalgesia, as well as inflammatory responses. The BV test might be a useful model of pain to evaluate and screen anti-nociceptive and anti-inflammatory effects of certain compounds of the Chinese medicinal herbs on the pathological origins of pain.
Analgesics ; pharmacology ; Animals ; Bee Venoms ; Drugs, Chinese Herbal ; pharmacology ; Female ; Formaldehyde ; Hyperalgesia ; physiopathology ; Inflammation ; chemically induced ; physiopathology ; Injections, Intravenous ; Male ; Nociceptors ; drug effects ; Pain ; chemically induced ; physiopathology ; Pain Threshold ; drug effects ; Pyrans ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Steroids ; pharmacology

ObjectiveTo investigate the correlation between the gross motor function and the clinical types and complications of children with cerebral palsy (CP).MethodsThe gross motor function of 126 CP children were measured by Gross Motor Function Classification System (GMFCS). Then the correlation between gross motor function, and clinical types and complications was analyzed.ResultsThere was a strong correlation between GMFCS and clinical types and complications ( P<0.001). GMFCS evaluation showed that 55.1% spastic children were categorized into levels Ⅰ and Ⅱ; 53.8% of dyskinetic and 85.7% of mixed children were categorized into levels Ⅳ and Ⅴ; 55.4% of diplegic and total hemiplegic children were categorized into levels Ⅰ and Ⅱ; 67.4% of tetraplegic and 55.6% complex hemiplegic children were categorized into levels Ⅳ and Ⅴ; 100% children with normal developmental quotient (DQ) and 91.6% above borderline of DQ were classified into levels Ⅰ and Ⅱ. The mental impairment was more severe; the levels of GMFCS were more higher. There were more visual impairment, hearing disorder, speech disability, feeding problem and epilepsy in children with levels Ⅲ, Ⅳ and Ⅴ than that with levels Ⅰ and Ⅱ.ConclusionThere is a significant correlation between GMFCS and clinical type and complications of CP, and the categorization of GMFCS is higher, the complications are more.