Fumaric acid esters (FAE), mainly dimethylfumarate (DMF), have been shown to be highly efficacious in the treatment of psoriasis. Among the potential side effects of FAE therapy, lymphocytopenia is sometimes observed. In order to address the question whether FAE may interfere with systems of the innate defense, the modulatory role of FAE on the generation of superoxide-anion by human monocytes and neutrophils was studied by measuring the reduction of cytochrome c. Various concentrations of DMF and its metabolite methylhydrogenfumarate (MHF) were used to observe their modulatory effect on superoxide-anion generation by monocytes and neutrophils in response to bacteria (S. aureus and E. coli) and candida (C. albicans). Dexamethasone (DXM, 1 x 10(-7) mol x L(-1)) was also studied at the same time. We found that DXM significantly inhibited superoxide-anion generation from monocytes in response to bacteria and C. albicans, whereas DMF and MHF (10-20 microg x mL(-1)) significantly increased the production of superoxide-anion in monocytes in response to the above mentioned bacteria. DXM, DMF and MHF did not affect superoxide-anion generation of neutrophils. Our data indicate that DMF and MHF enhance superoxide-anion generation in human monocytes as one of the important mechanisms of innate defense against microorganisms.
Candida albicans ; immunology ; Cells, Cultured ; Cytochrome c Group ; metabolism ; Dermatologic Agents ; pharmacology ; Dimethyl Fumarate ; Escherichia coli ; immunology ; Fumarates ; pharmacology ; Humans ; Phagocytes ; metabolism ; Staphylococcus aureus ; immunology ; Superoxides ; metabolism ; Zymosan ; immunology

OBJECTIVETo investigate the effect of triptolide on the differentiation of human Th17 cells.

METHODHuman peripheral blood mononuclear cells, purified CD4+ T cells and CD4+CD45RA- memory T cells were treated with various concentrations of triptolide in vitro. Cell proliferation was determined by MTT assay. Flow cytometry was used to analyze the intracellular expression of IL-17 and IFN-gamma. Cytokine production of IL-17 and IFN-gamma was measured by ELISA.

RESULTCell proliferation, intracellular expression of IL-17 and IL-17 secretion were inhibited by triptolide in a dose-dependent manner. IFN-gamma expression and production were also inhibited by triptolide.

CONCLUSIONTriptolide inhibits the differentiation of human Th17 cell. The observation may indicate at least one of the mechanisms of the immunosuppressive and anti-inflammatory effects of triptolide.

Anti-Inflammatory Agents, Non-Steroidal ; CD4-Positive T-Lymphocytes ; drug effects ; metabolism ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Epoxy Compounds ; pharmacology ; Humans ; Interferon-gamma ; drug effects ; metabolism ; Interleukin-17 ; metabolism ; secretion ; Phenanthrenes ; pharmacology ; Th17 Cells ; cytology ; drug effects ; Tripterygium ; chemistry

To investigate whether lithium carbonate, propranolol or chloroquine aggravate psoriasis through influencing cytokines of the psoriatic cytokine network, HaCaT keratinocytes were stimulated with TNF-a after treatment with these drugs. Protein secretion of a set of multiple different cytokines and growth factors in culture supernatants were measured by using a cytokine antibody array technology. Expression of IL-8 and IL-6 mRNA was determined by real-time PCR. In culture supernatants of TNF-alpha-stimulated HaCaT cells, production of IL-6 and TNF-alpha could be enhanced by lithium carbonate; production of IL-6 and a panel of cytokines and growth factors could be enhanced by propranolol hydrochloride; and IL-6 was up-regulated by chloroquine diphosphate as well. Real-time PCR analysis showed a significantly dose-dependent increase of IL-8 and IL-6 mRNA expression in HaCaT cells stimulated with TNF-a as compared to cells without TNF-alpha-stimulation, the mRNA expression of IL-8 was higher than that of IL-6 with the same concentration of TNF-alpha (P < 0.01). Compared with HaCaT cells cultured with medium alone, propranolol hydrochloride at the concentration of 1 x 10(-6) mol x L(-1) could stimulate HaCaT cells to express higher level of IL-6 mRNA (P < 0.05). The drugs investigated show a modulatory effect on certain cytokines and growth factors which are able to modulate inflammatory type of immune reaction present in psoriatic lesions.
Adrenergic beta-Antagonists ; adverse effects ; Antimalarials ; adverse effects ; Cells, Cultured ; Chloroquine ; adverse effects ; analogs & derivatives ; Humans ; Interleukin-6 ; biosynthesis ; genetics ; Interleukin-8 ; biosynthesis ; genetics ; Keratinocytes ; drug effects ; metabolism ; Lithium Carbonate ; adverse effects ; Propranolol ; adverse effects ; Psoriasis ; metabolism ; RNA, Messenger ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology

This paper was to study the angiogenic inhibitory effect and the potential antitumor effect of the constructed recombinant DNA vaccine CRT/HPV6bE7 in vivo. The C57BL/6 mice were vaccinated respectively with recombinant CRT/HPV6bE7 DNA plamids. The inhibitory effects on angiogenesis of generated vaccines in vivo were evaluated by a bFGF-induced angiogenesis assay using the Matrigel kit. To investigate the potential antitumor effect, the mean tumor weights, sizes and tumor appearing times were measured in C57BL/6 mice treated with HPV6bE7-expressing B16 cells. The results indicated that the recombinants CRT180/HPV6bE7 and CRT180 showed strong anti-angiogenic effects in bFGF-induced angiogenesis in vivo. Moreover, CRT180/HPV6bE7 and CRT180 DNA vaccines could significantly inhibit the tumor growth in tumor challenge experiment, and CRT180/HPV6bE7 was superior to other vaccines in delaying tumor formation time, limiting tumor size and weight in tumor protection experiment. In conclusion, recombinant CRT180/HPV6bE7 DNA could elicit a most efficient anti-angiogenic effect and inhibit tumor growth in mice inoculated with DNA vaccines. The antiangiogenic activity of CRT were suggested residing in a domain between CRT 120-180 aa.
Animals ; Calreticulin ; genetics ; Female ; Human papillomavirus 6 ; immunology ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; prevention & control ; Oncogene Proteins, Viral ; genetics ; Papillomavirus Infections ; therapy ; Papillomavirus Vaccines ; immunology ; Recombinant Fusion Proteins ; genetics ; Vaccines, DNA ; immunology

OBJECTIVETo determine Th1/Th2 cytokines and chemokines in patients with allergic diseases and its clinic significance.

METHODSSerum levels of IFN-gamma, IL-4, IL-5, IL-13, Eotaxin, RANTES and LTB4 were determined from peripheral blood of 64 allergic patients and 21 healthy controls with ELISA.

RESULTSIL-4, IL-5, IL-13 and Eotaxin, LTB4 were increased significantly in serum of allergic patients compared with those of controls (P<0.05). There were no significant differences in serum levels of IFN-gamma and RANTES between patients and controls (P>0.05). Serum levels of IL-4, IL-5, IL-13 and LTB4 were correlated with each other (P<0.01). Eotaxin, RANTES and IFN-gamma levels were also significantly correlated with each other (P<0.05). LTB4 was correlated with Eotaxin as well (P<0.01).

CONCLUSIONA wide range of cytokines and chemokines is involved in allergic diseases,which may play their roles in a complex interactive manner.

Adolescent ; Adult ; Aged ; Chemokines ; blood ; Child ; Child, Preschool ; Cytokines ; blood ; Female ; Humans ; Hypersensitivity ; blood ; immunology ; Interferon-gamma ; blood ; Interleukin-13 ; blood ; Interleukin-4 ; blood ; Leukotriene B4 ; blood ; Male ; Middle Aged ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Young Adult

Objective: To examine the modalities of treatment and clinical outcomes of emphysematous pyelonephritis (EPN), in order to improve the survival rate of EPN patients. Methods: Totally 14 patients diagnosed as EPN between October 2011 and November 2020 at Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were included in this article. Data collection including patient demographics, clinical manifestations, management and clinical outcomes were conducted by retrospective charts review, after receiving the institutional review board's approval. There were 11 females and 3 males with a median age of 59 years (range: 52 to 73 years). The lesions were located on the left side in 10 patients and right side in 4 patients. All the 14 patients suffered from fever, and present with severe sepsis or septic shock. The median time from symptom onset to admission to hospital was 3 days(range: 2 to 5 days). All cases had diabetes mellitus. Escherichia coli was the most common organism been cultured (11 cases), while Klebsiella pneumonia was the second (3 cases). CT scan showed bubbly or located gas in the renal parenchyma in 5 cases and presence of steaky or mottled gas in the renal parenchyma in 9 cases. All patients had been admitted to ICU for anti-septic shock therapy. Three patients had undergone percutaneous catheter drainage along with broad-spectrum antibiotics therapy while 3 patients had immediate nephrectomy, the other 8 cases had a combination of an initial percutaneous catheter drainage and second stage nephrectomy. Results: In this case series, 3 patients were died from EPN while the other 11 were survived. The median ICU stay time was 6 days (range: 3 to 11 days). Of the 3 patients died from EPN, 2 had undergone percutaneous catheter drainage along and 1 had received immediate nephrectomy. Among the 11 patients who were survived, only 1 had received percutaneous catheter drainage while the other 10 received nephrectomy (8 patients had staged nephrectomy). Follow-up was performed 6 months after discharge. Of the 11 surviving patients, 2 were lost to follow-up, and the remaining 9 patients had an creatine level of (118.4±29.4) μmol/L (range: 89 to 176 μmol/L). Conclusions: For patients coupled with diabetes who were initially diagnosed as acute pyelonephritis, the possibility of EPN should be considered when the disease progressed rapidly especially septic shock occurred. On the basis of empirical broad-spectrum antibiotics therapy and standardized anti-septic shock treatment, a combination of an initial percutaneous catheter drainage and second stage nephrectomy could be efficacious.
Aged ; Emphysema/therapy* ; Escherichia coli Infections ; Female ; Humans ; Male ; Middle Aged ; Pyelonephritis/therapy* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To evaluate the efficacy of ultrasound or fluoroscopic-guided percutaneous transluminal angioplasty (PTA) combined with thrombolysis for the treatment of acutely thrombosed arteriovenous fistula (AVF) or grafts (AVG). METHODS: One hundred and ninety-two hemodialysed patients, in whom the thrombosed arterio-venous AVF or AVG developed less than 72 h and there were no contraindications for thrombolysis and PTA, underwent PTA combined with thrombolysis therapy in Sir Run Run Shaw Hospital of Zhejiang University from October 2014 to October 2017. Under ultrasound and/or fluoroscopic guidance, balloon catheter was introduced to thrombosis sites along a guide wire. Then the balloon was inflated and normal saline mixed with urokinase and heparin was injected for thrombolysis. After blood flow was restored, angioplasty was performed on vascular stenosed sites. RESULTS: A total of 274 endovascular interventional operations were performed for 192 patients. The procedure success rate was 98.2%, clinical success rate was 93.8%and complication rate was 1.46%. The post-intervention primary patency rates for AVF group were 87.4%, 76.7%and 63.9%at 3, 6 and 12 months, respectively; while the post-intervention secondary patency rates were 93.7%, 91.6%and 83.0%, respectively. The post-intervention primary patency rates for AVG group were 60.7%, 51.5%and 43.1%at 3, 6 and 12 months, while the post-intervention secondary patency rates were 82.7%, 77.1%and 70.8%, respectively. CONCLUSIONS PTA combined with thrombolysis is an effective and safe therapeutic option for AVF and AVG thrombosis, which would prolong hemodialysis access and save vascular resources for hemodialyzed patients.
Angioplasty ; Arteriovenous Fistula ; Arteriovenous Shunt, Surgical ; Humans ; Renal Dialysis ; Retrospective Studies ; Thrombolytic Therapy ; Thrombosis ; surgery ; Treatment Outcome ; Ultrasonography

OBJECTIVETo explore the effect of clinical application of stand-alone MC+PEEK cage in anterior cervical fusion.

METHODSFrom January 2011 to January 2014,50 patients were treated with the MC+PEEK cage filled with autogenous cancellous illic-bone graft after anterior cervical discectomy. There were 22 patients with cervical spondylosis,26 patients with traumatic cervical disc herniation, 2 patients with cervical instability in these patients. There were 32 males and 18 females, aged from 30 to 79 years old with an average of 53.30 years old. There were 32 patients with single segment, 15 patients with double segments and 3 patients with three segments. Cervical AP and lateral and the flexion-extension X-rays were regularly taken in order to assess the cervical physiological curvature, the graft fusion and internal fixation related complications. Nerve function, clinical effect and bone fusion were respectively evaluated according to Japan Orthopedic Association (JOA), Otani grade and Suk method.

RESULTSAll patients were followed up from 6 to 36 months with an average of 20 months. No correlated surgical complications were found and all patients obtained bony fusion with an average time of 4.30 months. JOA score had significantly improvement after surgery (P < 0.05). The JOA score was 10.60 ± 3.00 before surgery and 16.10 ± 2.20, 16.40 ± 2.35 at one week and six months after surgery respectively. According to Otani grade,40 cases got excellent results, 9 good, 1 fair. No significant dysphagia and internal fixation related complications such as displacement of cages were found during the follow-up period.

CONCLUSIONUsing this cage in anterior cervical fusion can obtain satisfactory clinical effect with less operation injury and reduce the complications. It is a better fusion method in anterior cervical fusion.

Adult ; Aged ; Cervical Vertebrae ; surgery ; Female ; Humans ; Male ; Middle Aged ; Spinal Fusion ; adverse effects ; instrumentation ; methods

OBJECTIVETo investigate the role of T-helper (Th) and cytotoxic T (Tc) lymphocyte polarization in the pathogenesis of condyloma acuminatum (CA) and its correlation with recurrence.

METHODSThree-colour immunofluorescent flow cytometry was used to detect the proportion of CD3+ CD8- /IFN-gamma+ (Th1), CD3+ CD8- /IL-4+ (Th2), CD3+ CD8+/IFN-gamma+ (Tc1) and CD3+ CD8+ /IL-4+ (Tc2) cells in the peripheral blood of CA patients and health controls.

RESULTSCompared to health controls, CA patients showed a decreased number of Th1 (P < 0.01) and Tc1 cells (P < 0.05), as well as a decreased Th1/Th2 and Tc1/Tc2 ratio (P < 0.05). Furthermore, in 15 recurrent CA patients the ratio of Th1/Th2 was remarkably decreased (P < 0.01), while the ratio of Tc1/Tc2 had no significant change in comparison with health controls.

CONCLUSIONThe decrease of Th1 and Tc1 subsets results in relative Th2 and Tc2 predominance, and this tendency is more significant in recurrent CA patients. The Th1 to Th2 and Tc1 to Tc2 shifts in CA patients could be responsible for the fact that human papilloma virus (HPV) is hard to be eliminated.

Adult ; Aged ; Case-Control Studies ; Condylomata Acuminata ; blood ; immunology ; Female ; Flow Cytometry ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; T-Lymphocyte Subsets ; cytology ; immunology ; Th1 Cells ; cytology ; immunology ; Th2 Cells ; cytology ; immunology

Objective: To evaluate efficacy and safety of retrograde intrarenal stone surgery for treatment of upper urinary calculi. Methods: The clinical data of 640 patients with upper urinary tract calculi treated by retrograde intrarenal stone surgery (RIRS) in Renmin Hospital of Wuhan University from April 2016 to January 2019 were retrospectively analyzed. There were 424 males and 216 females. The awerage age was (46.2±12.8) years old, ranging 18 to 76 years old. The maximum diameter of the stone is (1.4±0.7) cm, ranging 0.6-3.2 cm. There were 126 cases with inferior calculi and 514 cases with non-lurgical calculi. There were 196 cases with unilateral ureteral calculi, 118 unilateral ureteral calculi cases with renal calculi, 236 cases with unilateral renal stones, and 90 cases with double kidney stones. 104 cases were placed with double J tube before operation and 496 cases were not placed before operation. There were 8 cases of horseshoe kidney, 30 cases of isolated kidney with renal insufficiency, 4 cases of pelvic ectopic kidney with dysplasia, 6 cases of congenital ureteral malformation and 2 cases of sponge kidney. Preoperative average hemoglobin was (133.2±5.6)g/L, ranging 126-188 g/L.And average serum creatinine was (84.4±12.2)μmol/L, ranging 74-242μmol/L before operation. All patients were treated with general anesthesia under the lithotomy position. The ureteroscopy combined with holmium laser lithotripsy was performed.The 200μm fiber was used, which the parameters were set as 12-45 W(0.5-1.5 J/10-30 Hz). The stone baskets were used to take stones according to actual conditions. The operation was performed by doctors of the same qualifications. Results: All patients underwent successful operation. The mean operation time was (45.6±14.6)min. The average postoperative hospitalization was (4.8±1.5)d. The postoperative serious complication rate was 0.9%, including(2 cases of sepsis and 1 case of subcapsular hematoma. Of the 640 patients, 596 were admitted to the hospital for a double J tube and 44 were lost of follow-up. 552 patients met the stone removal criteria, 44 patients did not meet the stone removal criteria for other treatments, such as extracorporeal shock wave lithotripsy, ureteroscopy or observed regularly. The stone-free rate (SFR) was 92.6% (552/596) after 1-3 months. On the first postoperative day, serum creatinine was (76.0±10.6)(58-156) μmol/L, and postoperative hemoglobin was (126.4±9. 6)(120-176) g/L. There was no significant difference in preoperative and postoperative hemoglobin (t=2.02, P=0.064). Preoperative and postoperative creatinine (t=64.76, P<0.05) was statistically significant. Meanwhile, the stone size (χ²=29.569, P<0.05) and position (χ²=44.949, P<0.05) versus SFR the impact was statistically significant. Multivariate regression analysis showed that stone size was not an independent risk factor for stone clearance (P=0.639). The stone position was an independent risk factor for stone clearance (P=0.013). Conclusions RIRS is a reliable treatment for small and medium calculi patients of the upper urinary tract. The curative effect of stone removal is clear, the complications are few, the safety is high. However, there are certain limitations to the efficacy in the treatment of large stones and lower calculi. Lower calculi is the independent risk factor for the treatment of efficacy.