Severe interstitial pneumonia caused by cetuximab: a case report and review of the literature.

Cetuximab is an IgG1 chimeric mAb against epidermal growth factor receptor, which can be used for chemotherapy failure or tolerance in patients with epidermal growth factor receptor expressed RAS wild-type metastatic colorectal cancer. We report on a patient who developed rapid-onset interstitial pneumonia while being treated with cetuximab plus XELOX (oxaliplatin, capecitabine) for metastatic colorectal cancer. A 75-year-old man patient was administered cetuximab plus XELOX regularly. After his cetuximab schedule was adjusted from 1 to 2 weeks, he rapidly developed interstitial pneumonia which led to acute respiratory distress syndrome. Our literature review indicated that, for patients with risk factors, a 2-week regimen of cetuximab might lead to interstitial pneumonia. Clinicians should closely monitor patients for adverse drug reactions to improve drug safety.

Identification of differentially methylated genes as diagnostic and prognostic biomarkers of breast cancer.

BACKGROUND: Aberrant DNA methylation is significantly associated with breast cancer. METHODS: In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis. RESULTS: In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994-1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976-1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival. CONCLUSIONS: Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.

Immunomodulatory activity of butanol extract from Solanum lyratum in tumor-bearing mice.

Solanum lyratum Thunb (Solanaceae) has been widely used for cancer as a folk remedy in Chinese traditional medicine. In this study, the main active fraction n-butanol extract from S. lyratum (BESL) was evaluated for the therapeutic efficacies on mice transplantable tumor and immunomodulatory potentials on the immune response in tumor-bearing mice. The effects of BESL on the growth of mouse transplantable S180 sarcoma, splenocyte proliferation, the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL), production of cytokines from splenocytes, and serum antigen-specific antibody levels in S180-bearing mice were measured. BESL could not only significantly inhibit the growth of S180 sarcoma transplanted in mice, but also remarkably promote splenocytes proliferation, NK cell and CTL activity, interleukin-2 and interferon-γ production from splenocytes, and serum antigen-specific antibody levels in tumor-bearing mice (P < 0.05, P < 0.01, or P <0.001). The results suggested that BESL might exhibit antitumor activity by improving immune response, and it could act as antitumor agent with immunomodulatory activity. This study provided evidence to understand the therapeutic effects of S. lyratum for treatment of cancer and a natural product to further researches to be developed as a cancer chemopreventive agent.

[Toll-like receptors and their role in pathogenesis and vaccine study of cutaneous diseases].

Toll like receptor (TLR) can specifically recgnize pathogen-associated molecular patterns (PAMPs) and is considered as an important link between innate and adaptive immunity. It has been shown that TLR plays an important role in the pathogenesis and pathophysiology of a variety of skin diseases. Moreover, TLR agonists have exhibited promising therapeutic effects on the disease models and are expected to be novel vaccine adjuvants. Investigations of the underlying mechanism will give new insights into these diseases. This review will discuss the relationship between TLR and pathogenesis and management of some cutaneous diseases.

[Electrophysiological changes in diabetic peripheral neuropathy patients of different Chinese medicine syndrome types intervened by naoxintong and mecobalamin].

OBJECTIVE: To investigate the intervention of Naoxintong and mecobalamin on electrophysiological changes in diabetic peripheral neuropathy (DPN) of different Chinese medicine (CM) syndrome types. METHODS: According to syndrome differentiation, 180 patients with DPN were classified as five syndrome types. And they were treated with Naoxintong (Group A), mecobalamin (Group B), and Naoxintong + mecobalamin (Group C). Four weeks was taken as one therapeutic course, and totally three courses. Their efficacies were assessed using clinical scoring, electrophysiological examinations, and ultrasonic examinations of the blood vessel inner diameter. RESULTS: (1) The motor nerve conduction velocity was obviously slowed down in the Gan-Shen deficiency syndrome (P<0.01). F-wave latency was obviously prolonged in the Gan-Shen deficiency syndrome and yang deficiency blood stasis syndrome (P<0.01). The skin sympathetic reflex latency was obviously prolonged in the qi deficiency blood stasis syndrome and phlegm stagnation collateral obstruction syndrome (P<0.01). (2) Statistical difference existed in the three groups of qi deficiency blood stasis syndrome (chi2 = 7.112, P<0.05) and Gan-Shen deficiency syndrome (chi2 =6.667, P<0.05). Of them, the total effective rate of qi deficiency blood stasis syndrome was 87.5% and the markedly effective rate 43.8% in Group A (P<0.05). The total effective rate of Gan-Shen deficiency syndrome was 100.0% and the markedly effective rate 50.0% in Group B (P<0.05). The total effective rate of qi deficiency blood stasis syndrome, yin deficiency blood stasis syndrome, phlegm stagnation collateral obstruction syndrome, yang deficiency blood stasis syndrome, and Gan-Shen deficiency syndrome was respectively 92.9%, 83.3%, 81.8%, 81.8%, and 75.0% in Group C. (3) Naoxintong and mecobalamin had some improvement of motor and sensory conduction of each CM syndrome type (P<0.05). Mecobalamin showed obvious effect on the skin sympathetic reflection (P<0.05). The nerve electrophysiological index of each syndrome types as well as the diameter of arteriae tibialis anterior could be improved in Group C (P<0.05). CONCLUSIONS: Naoxintong gained better effect in treatment of DPN patients of qi deficiency blood stasis syndrome by syndrome typing. Naoxintong combined with mecobalamin could be helpful for ameliorating DPN patients of each syndrome.

Effects of nursing intervention on lung infection prevention in patients with tracheotomy.

BACKGROUND: This study will evaluate the effects of nursing intervention (NIV) on lung infection prevention (LIP) in patients with tracheotomy. METHODS: The electronic databases of MEDLINE, Cochrane Library, EMBASE, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be retrieved from inception to the June 1, 2019 for randomized controlled trials investigating the effects of NIV on LIP in patients with tracheotomy without any language limitations. In addition, we will also search grey literature to avoid missing any potential studies. Two independent authors will perform study selection, data extraction, and risk of bias evaluation. RESULTS: This study will investigate the effects of NIV on LIP in patients with tracheotomy. The primary outcome is incidence of lung infection. The secondary outcomes include pulmonary function, quality of life, and complications post-surgery. CONCLUSION: The results of this study will summarize recent evidence for the effects of NIV on LIP in patients with tracheotomy.No ethic approval is needed in this study, because it will not need any individual data. The results of this study will be published at a peer-reviewed journal.

Increased endocytic activity in monocyte-derived dendritic cells in patients with psoriasis vulgaris.

BACKGROUND & OBJECTIVE: The understanding of the pathogenesis of psoriasis vulgaris has focused on T cell mediated immune disorder for many years. Recent studies provide evidence that dendritic cells may be of major importance as regulatory cells driving the psoriasis tissue reaction, and they are one of the therapeutic targets. In order to further characterize the role of dendritic cells in psoriasis, this study was designed to assess the differentiation of dendritic cells from monocytes (MoDC), the expression of phagocytosis related receptors by MoDC, their endocytic activity for fluorescent beads and lucifer yellow as well as their superoxide generation in patients with psoriasis. METHODS: Twenty eight patients with psoriasis vulgaris and 12 healthy controls were included in the study. MoDC were obtained by culturing monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days. Cell surface expression of CD1a, CD14, CD40, CD80, CD83, CD86, HLA-DR, mannose receptor (MR) and Fcg receptors by MoDC and their endocytosis of dextran and lucifer yellow were analyzed by flow cytometry. Zymosan ingestion was measured to access the phagocytosis of MoDC. RESULTS: Differentiation of monocytes to dendritic cells was upregulated in patients manifested as significantly increased expression of CD40, CD80, CD86 and HLA-DR compared with that in healthy controls (P<0.01). Expression of MR and Fcg receptor II (CD32) by MoDC was significantly increased in patients with psoriasis as well (P<0.01). Endocytosis of dextran but not lucifer yellow in patients was significantly higher than controls (P<0.01), and significantly enhanced phagocytosis by increasing zymosan ingestion was also observed (P<0.01) in patients. Taken together, endocytic and phagocytic activity of MoDC in psoriasis was increased than normal persons. INTERPRETATION & CONCLUSION: Enhanced activity of dendritic cells binding and capturing foreign antigens for subsequent antigen presentation and the initiation of immune responses in psoriasis may contribute to the pathogenesis of the disease. The upregulated expression of MR and the enhanced endocytic activity of DC might be an explanation for the absence of skin infection observed in psoriasis.

Triptolide affects the differentiation, maturation and function of human dendritic cells.

Triptolide is a purified component from a traditional Chinese herb Tripterygium wilfordii Hook F. It has been shown to have anti-inflammatory and immunosuppressive activities by its inhibitory effect on T cells. But the effect of triptolide on dendritic cells (DC) is unknown. Dexamethasone (Dex) is a classic immunosuppressive agent known to suppress the immune response at different levels and has recently found to modulate the development of DC, thereby influencing the initiation of the immune response. In this study, we investigated the affect of triptolide on the differentiation, maturation and function of DC differentiated from human monocytes (MoDC) in vitro in the presence of GM-CSF and IL-4. Dex was included in the study as a reference. Our data show that both triptolide and Dex prevented the differentiation in immature MoDC by inhibiting CD1a, CD40, CD80, CD86 and HLA-DR expression but upregulating CD14 expression, as well as by reducing the capacity of MoDC to stimulate lymphocyte proliferation in the allogeneic mixed lymphocyte reaction. They blocked the maturation of MoDC as totally blocked induction of CD83 expression and absent upregulation of CD40, CD80, CD86 and HLA-DR. In addition, higher concentration of triptolide (20 ng/ml) and 10(-6) M Dex induced apoptosis in MoDC as measured by expression of APO2*7 and DNA fragmentation (TUNEL assay). However, the phagocytic capacity of MoDC was enhanced by triptolide but not Dex. Therefore, the suppression of DC differentiation, the function in immature DCs as well as the inhibition of DC maturation by triptolide may explain some of its immunosuppressive properties. It is suggested that DCs are a primary target of the immunosuppressive activity of triptolide.

[A model for quantitative cigarette smoking and response of airways to cigarette smoke in guinea pigs].

OBJECTIVE: To establish an animal model for quantitative cigarette smoking and to determine the acute response of airways to cigarette smoke in guinea pigs. METHODS: The device for inhaling quantitative cigarette smoking was made, which was double pass and single-direction with the minimum dead space. The changes of airway resistance(R(L))and dynamic lung compliance(Cdyn) in guinea pigs exposed to compound air consisting of 75% cigarette smoke and 25% oxygen were observed. Exudation of Evans blue in pulmonary vessels was also determined after consecutive inhalation of 60 ml smoke. RESULT: The R(L) increased from the baseline of (0.21+/-0.05) cmH(2)O x ml(-1) x s to (0.37+/-0.13) cmH(2)O x ml(-1) x s after 10 consecutive breaths of cigarette smoke exposure(P<0.01). The Cdyn decreased to (61+/-19)% of baseline at the ninth to eleventh breaths (P<0.01). The exudations of Evans blue significantly increased in all measured parts of the airways such as lower trachea, main bronchi, proximal intrapulmonary airways and distal intrapulmonary airways (P<0.01). CONCLUSION: The model established in this study is useful for measuring the acute responses of airways induced by cigarette smoke in guinea pigs. Acute inhalation of cigarette smoke decreases dynamic lung compliance, increases airway resistance and vascular permeability of pulmonary vessels in guinea pigs.

Topical imiquimod treatment of cutaneous vascular disorders in pediatric patients: clinical evaluation on the efficacy and safety.

OBJECTIVE: To evaluate the clinical effect of topical imiquimod treatment on cutaneous vascular disorders in pediatric patients. METHODS: A retrospective investigation was conducted in 25 pediatric patients with cutaneous vascular disorders, including 19 infantile hemangiomas (IHs) (12 superficial/7 mixed type), 5 nevus flammeus (NF), and 1 pyogenic granuloma (PG). Imiquimod 5% cream was applied every other day for 4 to 16 weeks (average 9.6 weeks). RESULTS: Of the 19 IHs treated, an overall efficacy of 52.6% was achieved, with a clinical resolution rate of 15.8%, excellent rate of 26.3%, and moderate rate of 10.5%. The superficial type responded the best at 66.7%, while the mixed type showed only 28.6% effectiveness, which was predominantly from their superficial parts. No obvious response was noted in the 5 patients with NF. Side effects were observed in 78.9% of the patients, mostly mild to moderate local irritations and occasionally severe reactions such as thick crusting and ulceration. Systemic side events were observed in 4 IH patients including fever and digestive tract reactions. No recurrence was observed during the follow-up examination. CONCLUSIONS: Topical imiquimod could be an alternative option for the treatment of uncomplicated superficial IHs with satisfactory tolerability.

Toll like receptor agonists augment HPV 11 E7-specific T cell responses by modulating monocyte-derived dendritic cells.

Impaired local cellular immunity is one of the mechanisms responsible for condyloma acuminatum (CA) recurrence. The activation of dendritic cells (DCs) is important in vaccine development. We investigated the effect of different toll like receptor (TLR) agonists including LPS (TLR4 agonist), polyinosinic acid-polycytidylic acid (PIC, TLR3 agonist), CpG oligonucleotide (TLR9 agonist), and imiquimod (TLR7 agonist) on human monocyte-derived dendritic cells (mdDCs) loading of human papillomavirus (HPV) type 11 E7 epitope. As a result, we found that mdDCs loading HLA-A*0201-restricted HPV 11 E7 CTL epitope peptide could respond to the TLR agonists, especially LPS and PIC. This was characterized by an enhanced expression of CD40, CD80, CD86, CD83 and HLA-DR, and a high level of IL-12 production. TLR agonists, especially PIC, enhanced the ability of E7-loaded mdDCs to induce IFN-gamma-secretion CD4(+) naïve T cells. Moreover, E7-loaded mdDCs exposed to TLR agonists augmented autologous T cell responses including effector cytokines production and specific cytotoxic T lymphocyte (CTL) responses. In addition, the inhibitory effect of IL-10 on mdDCs maturation could be partially restored by LPS, PIC or imiquimod. Taken together, these results demonstrate that TLR agonists promoted the maturation of E7-loaded mdDCs and their ability to induce T help type 1 polarization and augment E7-specific T cell responses. These data also indicated that TLR3/4 agonists might be effective adjuvants of mdDC-based vaccines against CA.