Multivalent tyrosine kinase inhibition promotes T cell recruitment to immune-desert gastric cancers by restricting epithelial-mesenchymal transition via tumour-intrinsic IFN-γ signalling.

OBJECTIVE: Gastric cancer (GC) ranks fifth in incidence and fourth for mortality worldwide. The response to immune checkpoint blockade (ICB) therapy in GC is heterogeneous due to tumour-intrinsic and acquired immunotherapy resistance. We developed an immunophenotype-based subtyping of human GC based on immune cells infiltration to develop a novel treatment option. DESIGN: A algorithm was developed to reclassify GC into immune inflamed, excluded and desert subtypes. Bioinformatics, human and mouse GC cell lines, syngeneic murine gastric tumour model, and CTLA4 blockade were used to investigate the immunotherapeutic effects by restricting receptor tyrosine kinase (RTK) signalling in immune desert (ICB-resistant) type GC. RESULTS: Our algorithm restratified subtypes of human GC in public databases and showed that immune desert-type and excluded-type tumours are ICB-resistant compared with immune-inflamed GC. Moreover, epithelial-mesenchymal transition (EMT) signalling was highly enriched in immune desert-type GC, and syngeneic murine tumours exhibiting mesenchymal-like, compared with epithelial-like, properties are T cell-excluded and resistant to CTLA4 blockade. Our analysis further identified a panel of RTKs as potential druggable targets in the immune desert-type GC. Dovitinib, an inhibitor of multiple RTKs, strikingly repressed EMT programming in mesenchymal-like immune desert syngeneic GC models. Dovitinib activated the tumour-intrinsic SNAI1/2-IFN-γ signalling axis and impeded the EMT programme, converting immune desert-type tumours to immune inflamed-type tumours, sensitising these mesenchymal-like 'cold' tumours to CTLA4 blockade. CONCLUSION: Our findings identified potential druggable targets relevant to patient groups, especially for refractory immune desert-type/ 'cold' GC. Dovitinib, an RTK inhibitor, sensitised desert-type immune-cold GC to CTLA4 blockade by restricting EMT and recruiting T cells.

A case of IgG4-related interstitial nephritis with ureteral obstruction: case report and literature review.

BACKGROUND: IgG4-related disease (IgG4-RD) is a newly discovered systemic disease that can affect any organ or tissue in the body. IgG4-related kidney disease (IgG4-RKD) is relatively rare but essential to IgG4-RD. However, there are few reports of IgG4-RD mimicking malignant ureteral tumors leading to hydronephrosis. We report here a rare case of IgG4-RD involving the ureter. CASE PRESENTATION: An 87-year-old man presented to our nephrology department with anorexia, nausea, and acute kidney injury in November 2020. Urinary computed tomography (CT) examination revealed a right lower ureter mass with right renal and ureter hydronephrosis. The serum level of IgG4 was 1890 mg/dL, and the concurrently renal biopsy revealed extensive infiltration of IgG4-positive plasma cells in renal interstitium, which was diagnosed as IgG4-associated tubule-interstitial nephritis(IgG4-TIN). The renal function improved significantly after double-J tube implantation of the right ureter and moderate-dose hormone therapy. The serum IgG4 decreased to the normal range, and the right lower ureter mass almost disappeared after one year of low-dose hormone maintenance therapy. CONCLUSION: IgG4-RD can present as a mass in the renal pelvis and (or) ureter, leading to hydronephrosis. Therefore, early recognition of this disease is significant. Most patients respond well to hormonal therapy to avoid surgical treatment due to misdiagnosis as malignant tumors, causing secondary harm to patients.

Finite Element Analysis of Insertion Angle of Absorbable Screws for the Fixation of Radial Head Fractures.

OBJECTIVE: To investigate the biomechanical effects of different insertion angles of absorbable screws for the fixation of radial head fractures. METHODS: The finite element models used to simulate the fractures were created based on CT scans. Two absorbable screws were used to fix and maintain the stability of the fracture, and the angles between the screws were set to 0°, 15°, 30°, 45°, 60°, 75°, and 90°. A downward force of 100 N was applied at the stress point, which was coupled with the surface, and the distal radius was limited to six degrees of freedom. The direction and location of the applied force were the same in each model. The values of the von Mises stress and peak displacements were calculated. RESULTS: Under the applied load and different screw angles, the maximum von Mises stress in the screws was concentrated on the surface contacting the fracture surfaces. The maximum von Mises equivalent stress in the screw decreased when the angle increased from 0° (19.54 MPa) to 45° (13.11 MPa) and increased when the angle further increased to 90° (24.63 MPa). The peak displacement decreased as the angle increased from 0° (0.19 mm) to 45° (0.15 mm) and increased when the angle further increased to 90° (0.25 mm). CONCLUSION: The computational stress distribution showed that fixation with absorbable screws is safe for patients. Moreover, the minimum von Mises stress and displacements were generated when the angle between the screws was 45°; hence, this setting should be recommended for Mason type II radial fractures.

Biomarkers in Metabolic Syndrome Patients with Chronic Periodontitis.

OBJECTIVES: To investigate whether the levels of serum C-reactive protein (CRP), salivary interleukin (IL)-6 and IL-lß in metabolic syndrome (MS) patients can be potential monitors for inflammation in MS patients with severe periodontitis. METHODS: A total of 114 MS patients and 49 systemically healthy subjects were enrolled. CRP in serum and IL-1ß and IL-6 in non-stimulated whole saliva were collected from these patients and subjects and analysed by enzyme-linked immunosorbent assay (ELISA). Dental examinations were performed and the participants completed a questionnaire. RESULTS: The serum CRP level of MS patients was higher than that of systemically healthy subjects, and increased as the number of components increased (P < 0.05). No difference was observed in the salivary level of IL-6 and IL-1ß between MS patients and controls or between MS patients with different components. The level of salivary IL-6 in MS patients with moderate/severe periodontitis was significantly higher than in MS patients with good periodontal health/mild periodontitis (P < 0.05). After adjustment for age, sex and smoking habits, multivariate analysis showed that the corresponding odds ratio (OR) for MS combined with moderate/severe periodontitis was 1.21 (95% confidence interval [CI] 1.04-1.39, P = 0.012) for subjects with high serum CRP and salivary IL-6 and IL-1ß were not risk indicators for MS combined with moderate/severe periodontitis. CONCLUSIONS: MS patients might be burdened by high levels of serum CRP. Serum CRP could be a potentially valuable biomarker to detect inflammation in MS patients with severe periodontal disease.

Neurological manifestations of atrial myxoma: A retrospective analysis.

Atrial myxoma is the most common type of primary cardiac tumor and it is closely associated with stroke in adults. Early diagnosis and treatment of atrial myxomas is essential for the prevention of embolic events. The aim of the present study was to assess neurological complications associated with atrial myxoma. The neurological signs of atrial myxoma were retrospectively assessed in individuals who underwent treatment at West China Hospital (Chengdu, China) and The Affiliated Hospital of Hainan Medical University (Haikou, China), between March 2003 and February 2015. A total of 130 patients with atrial myxoma were included and 22 (17%) exhibited neurologic signs. These patients were aged 39.9±12.6 years (range, 13-78 years) and there were 13 female and 9 male patients. Ischemic cerebral infarct constituted the dominant clinical symptom (68.2%) and 3 patients exhibited concomitant cardiac manifestations. Atrial myxoma was diagnosed by echocardiography in all patients. Irregular surface of atrial myxomas was associated with a high risk of embolic events. The patients with myxoma successfully underwent surgery with no mortality recorded. In conclusion, atrial myxomas frequently manifest as cerebral infarction in individuals without cardiovascular risk factors. These tumors more commonly affect the middle cerebral artery. Irregular surface of myxomas appears to be associated with embolic events. Echocardiography may improve the diagnosis and early treatment of atrial myxomas.

[Clinical experience of resection for nasal skull-base tumors by microsurgical-assisted technique].

OBJECTIVES: To investigate the application of the microsurgical treatment in nasal skull-base tumors resection. METHODS: In a retrospective study, totally 15 cases with tumors in the nasal skull-base received microsurgical-assisted treatment in our department from February 2012 to June 2017 were analysed. Lateral rhinotomy approach was carried out in 11 patients and posterior wall of the maxillary sinus approach in 4 patients. RESULTS: Tumors of all cases were completely resected under the microscope. Postoperative bleeding, cerebrospinal fluid leakage, infection and meningo-encephalocele did not occur in this series. The postoperative follow-up time were 6 months to 5 years. One case lost follow-up, seven cases were survivor of tumor-free. Seven cases had recurrence or metastasis, with one case died and other six alive with tumor. CONCLUSIONS: Microsurgical-assisted resection for nasal skull-base tumors can obtain clear vision, with high surgical precision and security.

[Unilateral sinonasal disease in 376 adult patients: a retrospective study].

OBJECTIVES: To investigate the clinical and pathological features of patients with unilateral sinonasal disease (USD). METHODS: A retrospective analysis was completed on 376 adult patients with USD from January 2015 to December 2016. Their presenting symptoms, nasal endoscope, CT scanning, and pathology were analyzed respectively. RESULTS: Among the 267 (71.01%) patients with inflammatory disease, there were 4 pathological types. And there were 8 pathological types in 60 (15.96%) patients with benign tumor. Of the 49 patients with malignant tumor, there were 15 pathological types which included squamous carcinoma, malignant melanoma, and lymphoma, as well as myoepithelial carcinoma and Mesodermal mesoderm. The onset age of inflammation group was younger than that of benign (P<0.05) or malignant tumor groups (P<0.05). The misdiagnosis rate was 8.33% in benign tumor (5/60), and 10.20% in malignant tumor (5/49). Nasal polyps was the most common misdiagnosis in the groups of benign and malignant tumor. CONCLUSIONS: The pathology of adult patients with USD is complicated, and no specific clinical feature was found for distinguishing between benign and malignant lesions. The tumor took a quite proportion in adult patients with USD. Therefore, careful consideration should be taken before diagnosing patients with USD in order to reduce misdiagnosis rate.

Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type.

Macrophage polarization is flexible, and involves in different signaling pathways and various transcription factors. Suppressor of cytokine signaling (SOCS) is an important inhibitor of cytokine signaling pathways and also a key physiological regulator for natural and acquired immunity systems. Following transfection of SOCS1 short hairpin (sh)RNA into mouse macrophage cells, reverse transcription­quantitative polymerase chain reaction demonstrated that the mRNA levels of Janus kinase (JAK)1 and signal transducer and activator of transcription (STAT)1 increased significantly. In addition, western blotting indicated that JAK1, STAT1 and p­STAT1 expression was significantly enhanced. Fludarabine can inhibit phosphorylation of STAT1 and SOCS1 expression. When fludarabine was added and SOCS1 shRNA was transfected, the inhibition of fludarabine was weakened, and p­STAT1 expression was upregulated. Flow cytometry detection indicated that, following the downregulation of SOCS1 expression, M1­type cells significantly increased, but the proportion of M2­type cells did not change significantly. Fludarabine can reduce the effect of SOCS1 shRNA on promoting M1­type cell polarization, and macrophages can polarize into both M1 and M2 phenotypes. Further ELISA results presented that, when downregulating SOCS1 expression, interleukin (IL)­4 and IL­10 expression was both downregulated, and tumor necrosis factor (TNF)­α and interferon (IFN)­Î³ expression was significantly upregulated. When adding fludarabine or injecting with the traditional Chinese medicine Xuebijing, IL­4 and IL­10 expression was both significantly upregulated, and TNF­α and IFN­Î³ expression was significantly downregulated. When adding fludarabine and downregulating SOCS1, IL­4, IL­10, TNF­α and IFN­Î³ expression presented no significant changes. The above results indicated that, when SOCS1 expression is downregulated, it will activate the JAK1/STAT1 pathway, and thereby promote the polarization of macrophages into M1 type. The findings are of great importance for understanding occurrence, development and treatment of various immune­related diseases.

Soluble Egg Antigen Activates M2 Macrophages via the STAT6 and PI3K Pathways, and Schistosoma Japonicum Alternatively Activates Macrophage Polarization to Improve the Survival Rate of Septic Mice.

Sepsis is one of the most challenging health problems worldwide. Our previous study showed that chronic schistosoma japonica (SJ) infection might increase serum anti-inflammatory factors to play a protective role, thus improving the survival rate of septic mice. Further research revealed that SJ infection promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS-induced activation of M1 macrophages; up-regulated CD163, IL-10, and TGF-ß1 expression; inhibited TNF-α and iNOS expression; and blocked the effect of LPS-promoted TNF-α and iNOS expression. Furthermore, adoptive transfer of ex vivo programed M2 macrophages significantly increased the survival rate of septic mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played the same role as worm infection but had no impact on M1 macrophages. SEA reduced LPS-induced TNF-α and iNOS expression, decreased the inhibitory effect of LPS on IL-10 and TGF-ß1 expression, increased STAT6 phosphorylation, and up-regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K inhibitors were added, SEA-induced expression of CD163, IL-10, and arg1 might be reduced. Therefore, worm infection has a protective effect in septic mice in which SEA may play a key role via the STAT6 and PI3K pathways. This finding may provide a favorable solution for the treatment of sepsis, especially early cases. J. Cell. Biochem. 118: 4230-4239, 2017. © 2017 Wiley Periodicals, Inc.

Osteoprotegerin Promotes Cementoblastic Activity of Murine Cementoblast Cell Line in vitro.

OBJECTIVE: To investigate the effect of osteoprotegerin (OPG) on the cementoblastic activity of a clonal population of immortalised murine cementoblasts (OCCM-30) in vitro. METHODS: OCCM-30 cells were transiently transfected with the mouse OPG using the Avalanche transfection reagent. The ectopic expression of OPG was confirmed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. The cell counting Kit-8 assay was used to investigate the effect of OPG on cell proliferation. The expression levels of cementoblastic-related mRNA and protein in the transfected OCCM-30 cells were detected using real-time PCR, Western blotting and immunohistochemical staining. RESULTS: Satisfactory transfection efficiency was observed 48 h after transfection. The results of the cell proliferation assay indicated that the expansion rate of the OPG transfection group was greater than that of the control group at both 72 h and 96 h. The mRNA levels of osterix (Osx), protein kinase B (Akt1), cementum attachment protein (CAP) and osteopontin (Opn) were significantly upregulated (P < 0.05) in the OPG group. Protein levels of OPN, bone sialoprotein II (BSP II), osteocalcin (OC) and CAP, which are responsible for osteogenetic and cementoblastic activity, were significantly increased in the OPG-overexpressing group. CONCLUSION: Overexpression of OPG in OCCM-30 cells promotes cementoblastic activity.

Recombinant Trichinella spiralis 53-kDa protein activates M2 macrophages and attenuates the LPS-induced damage of endotoxemia.

Sepsis is a serious clinical condition of excessive systemic immune response to microbial infection. The pro-inflammatory stage of sepsis is generally launched by innate cells such as macrophages. They release inflammatory cytokines, activate other immune cells and cause severe tissue/organ damage. In this study, we have revealed that recombinant Trichinella spiralis (TS) excretory-secretory protein (rTsP53) exhibited anti-inflammatory properties and rescued mice from LPS-induced endotoxemia, which is a common model for sepsis study, potentially through the induction of M2 macrophages. rTsP53 treatment significantly decreased inflammatory cytokines (IL-6, IFN-γ and TNF-α) and increased IL-4, IL-10, IL-13 and TGF-ß secretion, both in circulation and in tissues. rTsP53 also induced the activation and infiltration of F4/80(+)CD163(+) macrophages to inflammatory tissues, increased M2 macrophage-related Arg1 and Fizz1 expression, and decreased M1 macrophage-related iNOS expression. PCR array showed that rTsP53 activated several genes that involve the survival of macrophages and also anti-inflammatory genes such as SOCS3. Together, our results show that rTsP53 activates M2 macrophages, which has strong anti-inflammatory potential to prevent LPS-induced lethal sepsis.

Micrometam C Protects against Oxidative Stress in Inflammation Models in Zebrafish and RAW264.7 Macrophages.

Micrometam C is a core of novel marine compound isolated from the mangrove associates Micromelum falcatum. In this study, we investigated the protective effects of micrometam C in inflammation models in the transgenic zebrafish line Tg (corola: eGFP) and RAW264.7 macrophages. We found that micrometam C significantly suppressed the migration of immune cells in tail-cutting-induced inflammation in transgenic zebrafish and reduced lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) in both zebrafish and macrophages. In addition, micrometam C also restored LPS-induced reduction of endogenous antioxidants, such as catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). The protective effects of micrometam C were in parallel to its inhibition of NADPH oxidase and nuclear factor-kappa-binding (NF-κB) activity. Thus, the present results demonstrate that micrometam C protects against LPS-induced inflammation possibly through its antioxidant property.

Influence of simvastatin on dopaminergic neurons of lipopolysaccharide-induced rat model of Parkinson's disease.

OBJECTIVE: To investigate the neuroprotective effects of simvastatin on lipopolysaccharide (LPS)-induced rat model of Parkinson's disease (PD) and the mechanisms involved. METHODS: Hemiparkinsonian rat models were induced by stereotaxieal injection of LPS in the right substantia nigra compacta. After 2 weeks of simvastatin treatment, rotational behavior test was performed after the intraperitoneal injection of apomorphine. Expression of tyroxine hydroxylase (TH) and glial fibrillary acidic protein were analyzed through immunohistochemical staining of substantia nigra and striatum, and the level of TNF- α was evaluated using enzyme-linked immunosorbent assay. RESULTS: Comparing with untreated group, behavioral symptoms of the rats were significantly less in the rats that received simvastatin treatment. The TH positive cell count in substantia nigra and striatum were significantly increased (P<0.05) and TNF- α expression was significantly decreased (P<0.05) in simvastatin group compared to untreated group. CONCLUSIONS: Simvastatin could effectively inhibit the activation of astrocytes, reduce TNF- α expression, and exert anti-inflammatory effects, and thus protect the dopaminergic neurons in substantia nigra and striatum of the rat model of PD.

Serum levels of specific IgE to Staphylococcus aureus enterotoxins in patients with chronic rhinosinusitis.

The aim of this study was to determine the prevalence of Staphylococcus aureus enterotoxins (SEs) in the serum from patients with chronic rhinosinusitis (CRS) and its involvement in the condition. Thirty CRS patients without nasal polyps (CRSsNP), 40 CRS patients with nasal polyps (CRSwNP), and 30 healthy controls were enrolled in this study. Peripheral blood was obtained and analyzed to measure the serum levels of total IgE, specific IgE to SEA, SEB and SEC, and eosinophil cationic protein (ECP) using ImmunoCAP assays. The positive rate and level of serum specific IgE to SEB, but not to SEA or SEC, were significantly higher in CRSwNP patients compared with the controls (P=0.027 and P=0.021, respectively). No significant differences were found between CRSsNP patients and controls, or between CRSsNP and CRSwNP patients. Serum total IgE was significantly elevated and positively correlated with SEB-specific IgE in the CRSsNP (P<0.001; r=0.393, P=0.032) and CRSwNP (P<0.001; r=0.581, P<0.001) groups. ECP was also significantly increased in the CRSsNP (P=0.002) and CRSwNP (P<0.001) groups, but not correlated with specific IgE to SEs in either CRS group. The results suggest that SEB may play a role in the pathogenesis of CRSwNP.

[Determination of bone metabolic marker levels in perio-implant crevicular fluid and analysis of dental implants stability by resonance frequency in the early stage of healing].

OBJECTIVE: To investigate the changes of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) level in perio-implant crevicular fluid (PICF) and to monitor the development of the stability of Straumann® tissue-level implants by resonance frequency analysis (RFA) during the early phases of healing. METHODS: A total of 35 implants (length 10 mm) were placed. PICF samples were collected with filter paper strips at baseline, 1, 2, 3, 4, 6, 8, and 12 weeks post-surgery, respectively. The OPG, RANKL levels were determined by ELISA method. At the same time points, the implant stability quotient (ISQ) values were determined with Osstell™ mentor. RESULTS: During healing, PICF-OPG levels increased significantly 2 weeks after surgery when compared with the 4(th) -, 6(th) -, 8(th) - and 12(th) -week reevaluation (P<0.05). The OPG/RANKL ratio in PICF was significantly higher (P<0.05) than that in gingival crevicular fluid at 1 week post-surgery. ISQ slightly fluctuated within the first 4 weeks after installation. Following this, the ISQ values increased steadily for all the implants and up to 12 weeks. Significant differences were noted between the mean ISQ values at the 12th-week and other observation time points. CONCLUSION: The PICF-OPG levels may be effective in monitoring the process of osseointegration. All the ISQ values indicated the stability of Straumann® implants over a 12-week healing period. RFA is a reliable and effective assistant to monitor implant stability.

Association between plasma leptin level and systemic inflammatory markers in patients with aggressive periodontitis.

BACKGROUND: Increasing evidence supports an association between periodontitis and systemic diseases. Leptin is involved both in the energy metabolism and inflammatory processes and is suggested to be a link between periodontal infection and systemic health. The present study aimed to evaluate the peripheral leptin concentration in patients with aggressive periodontitis (AgP) and to explore the relationship between leptin and systemic inflammation. METHODS: Ninety patients with AgP visiting the Clinic of the Periodontology Department, Peking University School and Hospital of Stomatology between July 2001 and May 2006, and 44 healthy controls (staff and student volunteers in the same institute) were recruited. Plasma levels of leptin and inflammatory cytokines including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay. Correlation and multiple linear regression analysis were performed to analyze the association between plasma leptin level and other variables. RESULTS: Plasma leptin level of AgP group was significantly higher than that of the control group (19.7 ± 4.4 ng/ml vs. 7.5 ± 1.3 ng/ml, P < 0.01). After controlling for age, gender, and body mass index, positive correlation was observed between plasma leptin concentration and log-transformed levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and CRP), and the partial correlation coefficients ranged from 0.199 to 0.376 (P < 0.05). Log-transformed IL-1ß and IL-6 levels entered the final regression model (standardized ß were 0.422 and 0.461 respectively, P < 0.01). CONCLUSIONS: Elevated plasma leptin concentration may be associated with increased systemic levels of inflammatory markers in AgP patients.

Safety and efficacy of S-1 chemotherapy in recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy: multi-institutional retrospective analysis.

PURPOSE: This retrospective study evaluates the efficacy and safety of S-1 chemotherapy for recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy. PATIENTS AND METHODS: Thirty-nine patients with recurrent and metastatic nasopharyngeal carcinoma who failed previous platinum-based chemotherapy received oral S-1 chemotherapy (twice daily from day 1 to 14) every 3 weeks. The dose of S-1 was determined according to the body surface area (BSA): 40 mg twice a day for BSA <1.25 m(2); 50 mg twice a day for 1.25 m(2) ≤BSA<1.5 m(2); and 60 mg twice a day for BSA ≥1.5 m(2). RESULTS: Treatment was well tolerated. Most adverse events were mild. Grade 3 hematological toxicity occurred in 7.7%. There was one complete response (2.6%) and 12 partial responses (30.7%), giving an overall response rate of 33.3% (95% CI [confidence interval], 21.7-50.8). Median time-to-progression was 5.6 months, and median survival was 13.9 months. One- and 2-year survival rates were 60% and 26%, respectively. CONCLUSION: S-1 monotherapy is considered a safe and effective treatment option for recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy.

Dexamethasone down-regulates the expression of microRNA-155 in the livers of septic mice.

To investigate the expression of microRNA-155 (miRNA-155) in the livers of mice with lipopolysaccharide (LPS)-induced sepsis and to determine the role of dexamethasone (DXM) in the regulation of miRNA-155 expression, we pretreated mice with or without DXM prior to LPS exposure. Our study demonstrated that the expression of miRNA-155 and inflammatory factors increased in the liver tissues of mice with LPS-induced sepsis and that DXM down-regulated their expression in a dose-dependent manner. Moreover, DXM alone inhibited the expression of miRNA-155 to below the baseline level, but did not impact the expression of inflammatory factors, suggesting that the down-regulation of miRNA-155 by DXM may partially, but not completely, depend on the suppression of pro-inflammatory cytokines by DXM. Our data indicate that the overexpression of miRNA-155 in the livers of mice with LPS-induced sepsis may play an important role in the pathological processes of sepsis and that the down-regulation of miRNA-155 by DXM may be a novel mechanism regulating inflammation and immunity.

Multicenter phase II study of capecitabine combined with nedaplatin for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy.

PURPOSE: There is no standard second-line regimen for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy. A multicenter phase II study was conducted to evaluate the efficacy and toxicity of capecitabine combined with nedaplatin for these patients. PATIENTS AND METHODS: In the multicenter, open-label, single-arm phase II study, patients with recurrent and metastatic nasopharyngeal carcinoma who failed to previous cisplatin-based chemotherapy were enrolled. Patients received oral capecitabine (1,000 mg/m(2) twice daily from day 1 to 14) and intravenous nedaplatin (80 mg/m(2), day 1) every 3 weeks for two cycles at least. RESULTS: A total of forty-eight patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. Treatment was well tolerated. Grade 3/4 toxicities included neutropenia (8.4 %), anemia (2.1 %), diarrhea (4.2 %), stomatitis (6.3 %), and hand-foot syndrome (HFS) (4.2 %). There were two complete response (4.2 %), eighteen partial responses (37.5 %), giving an overall response rate of 41.7 % [95 % confidence interval (CI) 27.7-55.8]. With a median follow-up period of 12.1 months, the median time to progression was 5.8 months (95 % CI 3.9-7.8 months) and median overall survival was 12.4 months (95 % CI 9.6-16.8 months). CONCLUSION: Capecitabine combined with nedaplatin offers a satisfactory clinical activity and an acceptable safety profile for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy.

CYP2C19 polymorphisms and antiplatelet effects of clopidogrel in acute ischemic stroke in China.

BACKGROUND AND PURPOSE: Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke. METHODS: A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated. RESULTS: The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance. CONCLUSIONS: CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke. Clinical Trial Registration Information- URL: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-12002681.