The overall 5-year survival rate for patients with metastatic colorectal cancer(CRC) is less than 10%.Median survival with 5-fluorouracil(5-FU)/leucovorin(LV) therapy is approximately 12 months.Recent additions to the chemotherapy armamentarium for this disease have begun to prolong median survival times.In trials in which patients are exposed to all three approved chemotherapy agents,oxaliplatin,irinotecan,and 5-FU/LV,or capecitabine during the course of their disease,median survival has reached 20 months. The addition of oxaliplatin and irinotecan to 5-FU/LV regimens has also led to the maintenance of quality of life for longer intervals than were traditionally observed with 5-FU/LV alone.Current standard first-line regimens for metastatic CRC are FOLFOX(infusional 5-FU/LV with oxaliplatin) and FOLFIRI(infusional 5-FU/LV with irinotecan).Ongoing investigations will identify a place for molecular targeted combination chemotherapy on metastatic colorectal cancer(CRC) and some trials achieved better efficiency.In this review,we discuss the current advances in combined management of metastatic colorectal cancer of 5-Fu,chemotherapy,Molecular targeted therapy.

Objective To investigate the alteration in gene expressions of collagen type Ⅰ and type Ⅲ in tissue of obstructive low compliant bladder of rats. Methods Gene expressions of collagen type Ⅰ and type Ⅲ in the rat bladder tissues were evaluated with RT-PCR. Results The gene expressions of collagen type Ⅰ and type Ⅲ in smooth muscle of low compliant bladder were up regulated, but the level of type Ⅲ gene expression was stronger than that of the type I. Conclusion Collagen type Ⅲ and Ⅰ gene expression was upregulated in tissue of obstructive low compliant bladder of rats. Up regulation of collagen gene expression was related to low compliant bladder after obstruction.

IgG4-related disease (IgG4-RD) is a newly recognized disease entity. IgG4-RD is characterized by a single or multiple masses in one or more organs; a lymphoplasmacytic infiltrate with a high percentage of plasma cells within the lesion staining for IgG4; a peculiar pattern of fibrosis known as "storiform" fibrosis; and elevated serum IgG4 concentrations. IgG4-RD can occur in various organs, including pancreas, kidneys, lungs, retroperitoneum, and prostate gland. The head and neck involvements of IgG4-RD have been chiefly described in Mikulicz disease (MD), Küttner's tumor, orbital? inflammatory pseudotumor, and idiopathic hypertrophic pachymeningitis (IHP) previously. Recent studies reported that IgG4-RD could also involve ear, nose and throat. Here we reviewed the literatures about ear, nose and throat involvement by IgG4-RD, in order to provide some theoretical bases for the diagnosis and treatment of IgG4-RD.
Autoimmune Diseases ; physiopathology ; Ear ; physiopathology ; Fibrosis ; Humans ; Immunoglobulin G ; Nose ; physiopathology ; Pharynx ; physiopathology ; Plasma Cells ; pathology

Objective To investigate the clinical characteristics and causes of recurrent purulent meningitis and its treatment.Methods The clinical data of 36 children with recurrent purulent meningitis were analyzed retro-spectively at Tianjin Children′s Hospital from 1 995 to 201 4.Based on the underlying illness,the following examinations were done respectively:brainstem electric response audi -ometry(BERA),temporal bone computed tomography,head magnetic resonance imaging(MRI),spinal core MRI,and blood immunoglobulin,etc.Results There were 24 boys and 1 2 girls involved in this study.The age of the initial onset in these patients ranged from 20 months old to 1 5 years old,with the average age of 5 year and 9 months old.There were 2 to 7 episodes in these cases.The etiology was identi-fied:1 9 cases (52.78%)with congenital anatomical abnormalities,1 2 cases of congenital inner ear malformation with cerebrospinal fluid (CSF) leakage,1 case of ear -nose CSF leakage,6 cases of pilonidal sinus.Fifteen cases (41 .67%)had anatomical abnormalities,1 2 cases had head and facial trauma,1 case had nasal polyps surgery,1 case (2.77%)had a history of chronic mastoiditis,and 1 case had a history of cochlear implant surgery;1 case of congenital humoral immunodeficiency disease X -linked agammaglobulinemia -free;1 case (2.77%)had humoral immunodefi-ciency disease.The anti -infection treatment was adopted in the acute -phase and then CSF rhinorrhea repair,CSF oto-rrhea,cerebrospinal fluid leakage,repair of the inner ear,pilonidal sinus resection,supplementary intravenous immuno-globulin around once every 3 months was given respectively in the restoration -phase.Thirty -three cases revealed no recurrence up to 8 months till 1 0 years follow -up,3 cases lost -to -follow -up.Conclusions The recurrent purulent meningitis is a serious infectious disease of the central nervous system,which may result in disabled condition even life -threatening.In order to avoid purulent meningitis recurrence,the corresponding treatment should be chosen ac-cording to different causes.

BACKGROUND:When peri-implantitis occurs, the levels of interleukin-17 in the peri-implant sulcular fluid and soft tissues are significantly increased, and there is a positive correlation with the depth of the peri-implant probing. However, because of the dual effects of bone absorption and protection, the function of interleukin-17 in peri-implantitis remains controversial, which should be further studied. OBJECTIVE:To retrospectively analyze the correlation between peri-implantitis and interleukin-17. METHODS: The first author searched Wanfang, CNKI and Medline databases from 1991 to 2014 by using key words of “dental implants, peri-implantitis, periodontitis, Th17 cels, interleukin-17, cytokines” in Chinese or English. The functions of bone destruction and protection of interleukin-17 in peri-implantitis were reviewed, and interleukin-17 expression and correlation with the peri-implantitis were detected. RESULTS AND CONCLUSION:According to the inclusion and exclusion criteria, 46 articles from 241 articles are selected. The results show that, noninvasive detection of the variation of interleukin-17 levels in peri-implant sulcular fluid or blood is conducive to the monitoring of early diagnosis and treatment of peri-implantitis. At present, most researches show the relationship between interleukin-17 and peri-implantitis, and there is a positive correlation between interleukin-17 and peri-implant probing depth. But other researches suggest that interleukin-17 acts as protector for bones, and there is no statistic significance in the level of interleukin-17 receptor gene in chronic peri-odontitis and healthy subjects. Therefore, the correlation between peri-implantitis and interleukin-17 remains to be further studied.

Objective To develop an interleukin-4(IL-4) antagonist named M5-IgG1Fc protein constructed by genetic engineering of antibody Fc fragment-cytokine mutein fusion protein which has a long half-life time in plasma.M5-IgG1 Fc protein binds to IL-4 receptor but cannot activate downstream signalling pathway , which provides a basis for drug develop-ment for allergic diseases .Methods The synthesized interleukin-4 mutant gene ( named M5 ) was cloned into the expres-sion vector pBV220 and transformed into E.coli DH5α.Chimeric gene M5-IgG1Fc obtained by overlap extension (SOE) method was transformed into glycoengineered Pichia pastoris GJK01 through expression vector pPICZαA .Then M5-IgGFc fusion protein was obtained by protein purification after being induced by methanol in 72 hours.The anti-IL-4 biologicial ac-tivity assay of M5 and M5-IgG1 Fc was performed with CTLL-2/IL-4R cells and detected with MTT colormetry .Finally,the half-life time of M5 and M5-IgG1 Fc protein in mice was compared by detecting the remaining amount in plasma with ELISA kit.Results The M5 protein expressed in E.coli and M5-IgG1 Fc fusion protein expressed in P.pastoris GJK01 both had IL-4 antagonistic bioactivity .The EC50 of both, which inhibited 5.6 ×10 -2 nmol/ml of IL-4, were 0.31 ±0.05 and 0.77 ± 0.03 nmol/ml,respectively.The maximum of M5 in plasma at 0.5 h was 5.8 ×10 -2 nmol/ml but the remaining amount was 2.8%of the maximum at 2 h.M5 protein could not be detected after administration at 8 h because of the detection line . The maximum of M5-IgG1 Fc fusion protein was 4.7 ×10 -2 nmol/ml,while fusion protein M5-IgG1 Fc decreased to 4.3%of its maximum at 120 h and could not be detected at 168 h.Conclusion M5 protein has IL-4 antagonistic bioactivity .M5-IgG1 Fc fusion protein expressed in glycoengineered P.pastoris GJK01 has IL-4 antagonistic bioactivity and long retention time in mice,which can be potentially used for treatment of allergic diseases .

Objective To evaluate the function of afferent neuronal pathways (ANP) from the lower urinary tract (LUT) in patients with spinal cord injury (SCI) by use of sympathetic skin response (SSR). Methods Twenty-one patients with SCI (13 cases of incomplete injury, and 8 cases of complete injury) were recruited as a SIC group and 8 healthy volunteers as a control group. SSRs of all subjects were evoked by means of electrical stimulation (ES) of the median nerve and perineal region,as well as bladder filling (BF), while SSRs of the right palm and sole were recorded using surface electrodes. Results SSRs induced by ES of the median nerve and perineal region, and also by BF in the control group were recorded. SSRs of palms and soles could be recorded by using ES of the median nerve in patients with incomplete SCI, who had desire to void. However, SSRs could not be evoked in 3 of 13 patients with incomplete SCI but without sensation of perineal skin. In 8 patients with complete SCI but without sensation of trunk skin and bladder, SSRs of palms and soles could not be induced during ES of the median nerve if injuries were located over T_3, and SSRs of palms were recorded when the injuries were located between T_(4~9), while SSRs of palms and soles were evoked if injuries were located under T_(10). However, SSRs of palms and soles could not be evoked by ES of perineal region and BF in all patients. Conclusion SSRs, evoked by BF, could concord with the subjective sensation of the subjects from the LUT, and reflect the integrity of ANP from LUT. There is difference between somatosensory and viscerosensory ANP.

Objective To investigate the relationship between aggrecan and YKL-40 in knee articular cartilage of Sprague-Daw-lay(SD) rats with osteoarthritis (OA) .Methods Fifty-six healthy SD rats were randomly divided into 7 groups ,8 cases per group . The one side of knee joint was randomly selected for performing the anterior cruciate ligment transection (ACLT) and establishing the OA model .The rats in one group were randomly killed on the day of operation and at postoperative 0 ,2 ,4 ,8 ,12 ,16 ,20 weeks . The femoral condyle cartilage samples at different time periods in the operated side were collected for conducting safranin O /fast green staining and HE staining .Meanwhile ,the OA pathological grade was made out according to the modified Mankin scale .The expression of aggrecan and YKL-40 in the cartilage with different stages of OA were analyzed by the immunohistochemistry meth-od ,and the status of expression were measured by average optical density (AOD) .The correlation between aggrecan and YKL-40 was analyzed .Results With the aggravation of OA ,the expression of aggrecan was gradually reduced and the expression of YKL-40 was gradually increased .The differences during the early ,middle and late phases of OA had statistical significance (P<0 .05) . The expression of aggrecan was negatively correlated with the expression of YKL-40(P<0 .05) .Conclusion The level of aggrecan is gradually reduced with the aggravation of OA .Aggrecan is negatively correlated with the YKL-40 level ,which may reflect the dedifferentiation degree of joint chondrocyte to some extent .

To study the effect of antioxidants R-(+)-lipoic acid (R-LA) on cells growth,proliferation and related mechanisms in human HepG2 cells lines.MTT was used to measure cells growth and proliferation.Reactive oxygen species (ROS) kit was used to analyze ROS level.Cell apoptosis and cell morphological changes were observed by flow cytometry and Hoechst 33258 test.Protein expression levels of apoptosis,autophagy and related pathway were analyzed through Western blot,including Bax,Bcl-2,caspase 3,PARP,ATG5,ATG7,LC3,Beclin1,mTOR,P70S6K,P38,P53,ERK and Akt etc.Results showed that cell growth and proliferation were inhibited in a dose-and time-dependent manner after being treated by lipoic acid.R-LA could increase ROS production,pro-apoptosis proteins Bax levels,activated caspase family and PARP.Meanwhile,R-LA could up-regulate the levels of autophagy-related proteins including ATG5,ATG7,Beclin1 and LC3,and down-regulate phosphomTOR and P70S6K levels.Signal pathway results showed that R-LA could up-regulate phospho-P38 and phospho-JNK levels,and decrease phospho-Akt and phospho-ERK.When adding 3-methyladenine,autophagy was inhibited.Thus,R-LA might activate autophagy and induce apoptosis by P38/AMPK-JNK,PI3K/AKT and Ras/ Raf/MEK/ERK pathways.

Objective To explore the inhibiting effects of arsenic trioxide and cisplatin on MG-63 cells. Methods Using MTT assay,flowcytometry,phase contrast microscopy and electron microscopy methods,the therapeutic effect of arsenic trioxide was studied for the osteosarcoma in the cultured MG-63 cells in vitro,and compared these effects with cisplatin. The inhibitory rotes of cell growth and the effect of apoptosis and cell cycle were compared between arsenic trioxide and cisplatin on MG-63 cells. Results The contrast phase microscope revealed the adhesion ability of normal groups was good and cellular morphology showed epithelium cells. But the celhdar morphology showed irregular arrangement in arsenic trioxide groups and cytoplasmic vacuoles in cisplatin group. Electron microscope revealed the globular plasmalemma ecphymas in cell surface of control groups,the enlarged crista mitochondriales and the double-deck membrane structure appeared clearly. But electron microscope revealed globular plasmalemma processes in cell surface of arsenic trioxide groups,thinned crista mitochondriales and clearly seen karyopycnosis and nuclear membrane of apoptotic cells. The globular plasmalemma processes in cell surface of cisplatin groups were separated,nuclear membrane thickened and chromatin were in sandy shape. Both arsenic trioxide and cisplatin inhibited effectively MG-63 cells growth. There was a significant difference in different groups of inhibition ratios to the growth of cells(all P < 0.05). In 2,4,8,16,32,64,128 hours,the inhibition ratios(%) of arsenic trioxide(56.31±0.03,70.00±0.06,79.84±0.03,87.31±0.13,84.70±0.09,90.68±0.06,91.18±0.05) and cisplatin groups(7.55±0.15,15.70±0.17,30.72±0.07,49.80±0.05,45.11± 0.13,61.62±0.08,93.80±0.12) were obviously increased as compared with those in the control group(2.03± 0.07,2.78±0.08,3.11±0.01,5.67±0.04,12.23±0.04,18.65±0.04,24.45±0.04,all P < 0.05). Moreover the inhibition ratio of arsenic trioxide group in 2 to 32 hour was significantly higher than that of cisplatin group and the effect was more faster(all P < 0.05). Both arsenic trioxide and cisplatin could induce apoptosis MG-63 cells. There was a significant difference in different groups of the inhibition ratio to the growth of cells(F = 13.317,P < 0.05). The inhibition ratios(%) of arsenic trioxide on 24,36,48 hour(20.50±3.78,45.76±9.90,25.16±15.41),and cisplatin groups on 24,36,48 hour(12.55±1.51,18.85±3.40,12.37±5.43),were obviously increased as compared with those in the control group at the same time(6.57±1.48,8.03±2.08,6.54±1.30,P< 0.05 or<0.01). Both arsenic trioxide and cisplatin inhibited MG-63 cells cycle. There was a significant difference in different groups of the inhibition ratio to the growth of cells(F = 54.579,43.429,21.795,P < 0.05 or < 0.01). And the total inhibition ratios(%) in G1 cycle of arsenic trioxide(78.26±5.24) and cisplatin groups(80.48±2.81) were obviously increased as compared with those in the control group(57.49±6.65,all P < 0.05 or < 0.01). Conclusions Arsenic trioxide and cisplatin can effectively inhibit the proliferation of MG-63 cell line and induce the apoptosis of MG-63 cell line. And the effects induced by arsenic trioxide group were faster than that of cisplatin groups. Moreover arsenic trioxide can arrest the cell cycle of MG-63 cell line at G1 phase.