Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.

Objective - To analyze the relationship between cobalt level of post shift urine and individual exposure level of ， cobalt and its compounds in cobalt exposed workers and to explore the feasibility of using urine cobalt as a biomarker. Methods - A total of 148 occupational cobalt exposed workers from a new material company were selected as the exposed ， - - group and 44 non occupational cobalt exposed workers from the company were selected as the control group using the typical sampling method. The exposure concentration of time weighted average of cobalt and its compounds in the workplace air of the - two groups was determined by inductively coupled plasma mass spectrometry as the individual exposure level. The cobalt levels - - of pre shift and post shift urinary samples of the two groups were detected by this method. The linear relationship between the - cobalt level of post shift urine and the individual exposure level of cobalt and its compounds in the air of the workplace was Results - 3 analyzed. The individual exposure level of cobalt and its compounds in the exposed group was 1.10 131.71 μg/m with （M） 3 the median of 12.23 μg/m. No cobalt and its compounds were detected in the workplace air in the control group. The cobalt - - levels of pre shift and post shift urines in exposed group were higher than those in the control group at the same time point （M： vs ， vs ， P ） - - 1.54 0.56 μg/L 8.77 0.83 μg/L all <0.01 . The cobalt level of post shift urine was higher than that in pre shift （M： vs ，P ）， urine in the exposed group 8.77 1.54 μg/L <0.01 and it was positively correlated with the individual exposure level （ ，P ） ， of cobalt and its compounds Spearman correlation coefficient=0.86 <0.01 . After common logarithm conversion the linear regression equation of the cobalt level of post shift urine and the common logarithm of individual exposure level of cobalt and （x） ：ŷ x（ ；F ， its compounds in the exposed group was as follows = −0.178 + 0.988 coefficient of determination=0.72 =374.75 P ；t ， P ） Conclusion - <0.01 = - 19.36 <0.01 . There was a linear correlation between cobalt level of post shift urine and occupational cobalt exposure level of cobalt exposed workers. Urinary cobalt can be used as a biomarker of occupational cobalt

Syndrome of resistance to thyroid hormone(RTH)is a rare hereditary thyroid disease with various clinical manifestations and laboratory findings. RTH could be misdiagnosed and mistreated, resulting in aggravation of the disease. We reviewed the medical records of a patient with RTH over the past six years. In addition, we provided a summary of latest progress for RTH to help the clinicians to improve the understanding of the disease.

Objective:To analyze the false positive rate and false negative rate of layered mammography in diagnosis of mammary gland diseases.Methods:120 patients with malignant breast diseases and 120 patients with benign breast diseases treated in Huadong Hospital Affiliated to Fudan University from February 2015 to October 2016 were selected.All patients were examined by both traditional mammography and layered mammography.Taking surgical pathology as the gold standard,the diagnostic value of the two methods on patients with different ages,different lesion sizes,and different gland texture were compared.Results:The false positive rate and false negative rate of patients with mammary gland diseases in layered mammography group aged less than 45 years,45-60 years,and more than 60 years were lower than those of the conventional group,and the differences were statistically significant (P＜0.05).The false positive rate and false negative rate of patients with mammary gland diseases in layered mammography group with lesion sizes less than 1 cm,1 2 cm,and more than 2 cm were significantly lower than those of the conventional group,and the differences were statistically significant (P＜0.05).As for the patients with different gland texture,the false positive rate and false negative rate of the two groups were not statistically different.Conclusions:The false positive rate and false negative rate of layered mammography in diagnosis of breast diseases are lower than the conventional mammography,so it has higher clinical diagnostic value.

Objective To establish a rabbit model of facial skin lifting and to evaluate the skin lifting effects of absorbable soft tissue plastic belt, and to provide experimental basis for clinical application of this plastic belt.Methods 36 Japanese white rabbits were randomly divided into model control group (n=6) and plastic belt lifting group (n=30). The model control group received only facial skin resection surgery, while the plastic belt lifting group had facial skin resection and plastic belt implantation.The changes of rabbit general status, skin lifting effects, performance of plastic belt and pathological changes of subcutaneous tissue after implantation were determined during the 4 weeks after surgery. Results The rabbit skin wound was healed within 3-7 days after surgery without infection.Meanwhile, the plastic belts did not show shifting or rupture, and only whitening around the perforations was observed in the two groups.Compared with the model control group, the MA and MB distances in the plastic belt lifting group were significantly lower ( P<0.01 ) , while the biological tension of plastic belts in the facial skin lifting rabbit models was significantly increased with the extension of time after implantation (P<0.01), and the biological tension was 18.62 N at 4 weeks after transplantation. In addition, the tensile intensities of perforations and plate in the two groups were significantly reduced at 4 weeks postoperatively (P<0.01), the tensile intensity of perforations and plate in the two groups were maintained at 35.07 N and 53.31 N, respectively, and the perforations/plate tensile intensity ratio of the two groups remained unchanged during 4 weeks after transplantation ( P >0.05 ) .Moreover, the molecular weight ( Mw ) , peak molecular weight ( Mp ) , Z molecular weight (Mz) and viscosity were gradually decreased along with the time passing after implantation (P<0.01), and its dispersion Mz/Mw ratio was also gradually decreased from 2 weeks after implantation (P<0.01), and no obvious pathological changes were found after subcutaneous implantation of the plastic belts.Conclusions We have successfully established a facial skin lifting rabbit model, and the plastic belt can obviously lift the facial skin fascia system and keep intact more than 4 weeks in the body.Therefore, this plastic belt can be applied for anti-wrinkle facial soft tissue lifting against the skin damage caused by aging.

OBJECTIVETo evaluate the preliminary curative effect of interspinous injections for the diagnosis and treatment of back pain caused by lumbar kissing spine (Baastrup's disease) under fluoroscopically guiding.

METHODSFrom November 2011 to March 2013,17 patients with back pain caused by Baastrup's disease were treated with fluoroscopically-guided interspinous injections, including 7 males and 10 females with an average age of 49.6 years old ranging from 40 to 71 years old; the duration of the disease ranged from 2 to 5 years with a mean of 3.7 years. The visual analogue scale (VAS) and the lumbar segments range of motion (ROM) was analyzed at pre-operation, 2 days, 3 months and final followed-up after operation, the effects were evaluated with modified Macnab standard.

RESULTSAll patients were follow-up from 6 to 10 months with an average of 7.6 months. The pre-operative VAS was 6.41 +/- 0.94, the postoperative VAS at different time points improved significantly comparing with pre-operation,and the differences were statistically significant (P < 0.01). There was no significant difference in VAS at different time points after operation (P > 0.05). The ROM of operated segment and adjacent segment was (4.88 +/- 0.86) degrees and (6.82 +/- 0.73) degrees respectively at pre-operation. The postoperative operated segment ROM at different time points improved significantly comparing with pre-operation, and the differences were statistically significant (P < 0.05). Compared with pre-operation, there was no significant difference in adjacent segment ROM at different time points after operation (P > 0.05). According to modified Macnab, the result was excellent in 6 cases, good in 7 cases, fair in 3 cases and poor in 1 case.

CONCLUSIONFluoroscopically-guided interspinous injections is an effective method for the diagnosis and treatment of Baastrup's disease. The method has advantages of simple operation, minimal invasion and safety, satisfactory short-term and medium-term therapeutic effect; it can also effectively lessen the pain of lumbar and back.

Adult ; Aged ; Anesthetics, Local ; administration & dosage ; Female ; Humans ; Low Back Pain ; diagnosis ; diagnostic imaging ; drug therapy ; Lumbar Vertebrae ; diagnostic imaging ; drug effects ; Male ; Middle Aged ; Nerve Block ; Spinal Diseases ; diagnosis ; diagnostic imaging ; drug therapy ; Tomography, X-Ray Computed

Objective:To evaluate the preliminary curative effect of interspinous injections for the diagnosis and treatment of back pain caused by lumbar kissing spine (Baastrup's disease) under fluoroscopically guiding. Methods:From November 2011 to March 2013,17 patients with back pain caused by Baastrup's disease were treated with fluoroscopically guided inter-spinous injections,including 7 males and 10 females with an average age of 49.6 years old ranging from 40 to 71 years old;the duration of the disease ranged from 2 to 5 years with a mean of 3.7 years. The visual analogue scale (VAS) and the lumbar seg-ments range of motion (ROM) was analyzed at pre operation,2 days,3 months and final followed up after operation,the effects were evaluated with modified Macnab standard. Results:All patients were follow up from 6 to 10 months with an average of 7.6 months. The pre operative VAS was 6.41±0.94,the postoperative VAS at different time points improved significantly comparing with pre operation,and the differences were statistically significant (P<0.01). There was no significant difference in VAS at different time points after operation (P>0.05). The ROM of operated segment and adjacent segment was (4.88±0.86)° and (6.82±0.73)° respectively at pre operation. The postoperative operated segment ROM at different time points improved signifi-cantly comparing with pre operation,and the differences were statistically significant (P<0.05). Compared with pre operation, there was no significant difference in adjacent segment ROM at different time points after operation (P>0.05). According to modified Macnab,the result was excellent in 6 cases,good in 7 cases,fair in 3 cases and poor in 1 case. Conclusion:Fluoro-scopically guided interspinous injections is an effective method for the diagnosis and treatment of Baastrup's disease. The method has advantages of simple operation,minimal invasion and safety,satisfactory short term and medium term therapeutic effect;it can also effectively lessen the pain of lumbar and back.

Objective To investigate the relationship between hepatitis B virus (HBV)deoxyribonucleic acid (DNA) and HBV covalently closed circular DNA (cccDNA) in the ovary and HBV intrauterine infection.Methods HBV DNA and HBV cccDNA were assayed in the ovaries of 33 pregnant women who were positive for HBV DNA,tested by Fluorescent quantitative polymerase chain reaction (FQ-PCR).The level of HBV mark (HBVM) and the content of HBV DNA in peripheral blood of infants were measured by chemoluminescence and FQ-PCR methods respectively.Results The overall positive rate for both HBV DNA and HBV cccDNA in ovarian samples was 51.52％ (17/33).The rate on intrauterine infection among infants was 12.12％ (4/33) and all the 4 infected infants were delivered from mothers with normal hepatic function.When HBV DNA and HBV cccDNA were both positive,the rate of intrauterine infection in infants was significantly higher than those who were with both negative results (P＜0.05).Levels of HBV cccDNA and the rate of positive samples were significantly higher in mothers with infants who appeared to have had intrauterine infection than those did not (P＜0.01 and ＜0.05,respectively).Conclusion HBV infection could be discovered in the human ovary and might be transmitted to the filial generation via ovum.

BACKGROUNDThe tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor.

METHODSA total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010. Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib mono-therapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. We divided patients into Group A and Group B according to the blood pressure level.

RESULTSThe median follow-up was 15 months (10 cycles, range 1.5 - 30.0 months (1 - 20 cycles)). Ten patients (29.4%) achieved partial responses (PR); 23 patients (67.6%) demonstrated stable disease (SD) lasting ≥ 2 cycles. Seventeen patients (50%) developed progressive disease (PD) during follow-up. The median progression-free survival (PFS) was 15 months (range 3.0 - 28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 months (range 7 - 24) months. The most common adverse events were hand-foot syndrome (77.8%), thrombocytopenia (75.0%), hypertension (61.1%) and diarrhea (46.0%). Most adverse events were reversible by treatment interruption. Twenty-two patients (61.1%) developed hypertension; and hypertension was associated with a long time to disease progression and long overall survival (P = 0.004, 0.000, respectively).

CONCLUSIONSThe results of this study demonstrate the efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic clear cell RCC. Further, sunitinib-associated hypertension may be a strong predictive marker for treatment efficacy in metastatic RCC.

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Carcinoma, Renal Cell ; drug therapy ; mortality ; Drug Administration Schedule ; Female ; Humans ; Indoles ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the clinical effects of the minimal invasive osteotomy treatment for hallux valgus combined with tailor's bunion deformity.

METHODSFrom May 2007 to May 2009, Forty-nine feet of 32 patients (a mean age of 57 years old) of hallux valgus combined with tailor's bunion deformity were reviewed retrospectively, including 2 males(2 feet) and 30 females (47 feet). All patients were treated by the minimal invasive osteotomy. The axial and lateral films of all feet with loading were taken before and after operation. The hallux abducto valgus angle(HAV),intermetatarsal angle(IM), fourth-fifth intermetatarsal angle (IM 4 to 5), modified fourth-fifth intermetatarsal angle (MIM 4 to 5), Metatarsophalangeal-fifth angle (MPA) and lateral deviation of the fifth matatarsal angle (LDA) were compared before and after operation. Therapeutic effects of all the patients were observed after operation, the item including AFAS score and WEN Jian-min's therapeutic effects standard.

RESULTSThe average operating time was 40 minutes. All the patients were followed up,and the duration ranged from 6 to 24 months. The HAV angle, IM angle, IM 4 to 5 angle, MIM 4 to 5 angle,MPA angle and LDA angle significantly decreased after operation. The AFAS score significantly raised after operation. According to the criteria, 33 feet got an excellent result, 15 good and 1 fair.

CONCLUSIONThe minimal invasive osteotomy treatment for hallux valgus combined with tailor's bunion is effective and safe. This method is mini-trauma,less pain and it can make a very soon rehabilitation. This method has widely clinical value.

Adult ; Aged ; Aged, 80 and over ; Bunion, Tailor's ; surgery ; Female ; Hallux Valgus ; surgery ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Osteotomy ; methods