Unusual presentation of a first branchial arch fistula with maxillofacial infection: a case report.

BACKGROUND: First branchial cleft anomaly (FBCA) is a rare congenital defect that arises due to incomplete closure of the ventral portion of the first and second branchial arches. There are variable complex clinical manifestations for patients with FBCA, which are prone to misdiagnosis and inadequate treatment. FBCAs usually involve the facial nerve with a consequent increased risk of facial nerve damage. Here, we present an unusual case of FBCA presenting with two preauricular pits in association with an abnormal maxillofacial cyst. CASE PRESENTATION: A 10-month-old girl presented to our department due to recurrent maxillofacial infections accompanied by swelling or abscess of the left cheek and purulent discharge from the preauricular pit for 4 months. A 3D-computed tomography (CT) fistulogram and magnetic resonance imaging (MRI) revealed two conjunctive tract lesions: one tract arose from the skin surface anteroinferior to the external auditory canal (EAC), through the deep lobe of the left parotid, and anteriorly extended to the left masseter; the other extended from the superficial lobe of the left parotid to the intertragic notch. After the maxillofacial infection was controlled by intravenous antibiotic administration, surgery was performed. Intraoperative tools, such as facial nerve monitors, microscopes, and methylene blue dyes, were used to facilitate the complete dissection and protection of the facial nerve. On follow-up over one year, the patient recovered well without facial palsy or recurrence. CONCLUSION: FBCA with maxillofacial cysts is rare and prone to misdiagnosis. Physicians should pay attention to this anatomic variant of FBCA with the fistula track located deep inside the facial nerve and projected medially to the masseter.

Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma.

BACKGROUND: Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). However, many ER-positive patients are low reactive or resistant to tamoxifen. Metformin is a widely used anti-diabetic drug with noteworthy anti-cancer effects. We investigated whether metformin has the additive effects with tamoxifen in ER-positive breast cancer therapy. METHODS: The efficacy of metformin alone and in combination with tamoxifen against ER-positive breast cancer was analyzed by cell survival, DNA replication activity, plate colony formation, soft-agar, flow cytometry, immunohistochemistry, and nude mice model assays. The involved signaling pathways were detected by western blot assay. RESULTS: When metformin was combined with tamoxifen, the concentration of tamoxifen required for growth inhibition was substantially reduced. Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells. In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Finally, two-drug combination therapy significantly inhibited tumor growth in vivo. CONCLUSION: The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer.

Causal Relationship Between Body Mass Index and Risk of Otitis Media with Effusion in Children: A Mendelian Randomization Study.

Background: Body mass index(BMI) in children appears to be associated with Otitis media with effusion(OME) in observational studies, but the causal relationship is not clear. Methods: A two-sample Mendelian randomization (MR) study was used to explore the causal relationship between childhood BMI and OME in people of European ancestry. Genome-wide association studies (GWAS) of childhood BMI were used as exposures (n = 61,111), while GWAS of OME were used as outcomes (n = 429,290). The weighted inverse variance method (IVW) was used as a baseline method to test for causality. In addition, MR-Egger, simple mode analysis, weighted median, and weighted mode were used as complementary methods.MR-PRESSO analysis, MR-Egger intercept analysis, and Cochran's Q statistical analysis were also used to detect possible directional heterogeneity and polymorphism. To assess this association, we used ratios (OR) with 95% confidence intervals (ci). All statistical analyses were performed in R. Results: We selected 22 genome-wide significant single nucleotide polymorphisms (SNPs) from GWAS as instrumental variables (IVW). the IVW approach showed evidence supporting a causal relationship between BMI and OME in children (ß = 0.265, SE = 0.113, P = 0.018). MR-Egger regression showed that targeted polymorphisms were unlikely to bias the results bias (intercept=-0.022; P = 0.488), but there was no causal relationship between BMI and OME (ß = 0.584, SE = 0.465, P = 0.224). Although the results of the IVW and MR Egger analyses were not consistent, the IVW analysis maintained higher precision, and the Cochran Q test, heterogeneity and polymorphism tests showed no heterogeneity, no directionality and no polymorphism. Conclusions: MR studies suggest that genetically predicted body mass index in childhood is associated with an increased risk of OME. Notably, given the limitations of this study, the mechanism of association between body mass index and OME in childhood needs further investigation. These results support the importance of effective management of obesity, which may reduce OME occurrence and decrease OME recurrence.

Meningocele in the Parapharyngeal Space: A Case Report and Review of the Literature.

The parapharyngeal space has been described as an inverted pyramid shape with the base of the skull and the great cornu of the hyoid bone at the top. Tumors of the parapharyngeal space account for 0.5% of head and neck tumors and a wide range of tumor types can occur in this area, 80% of which are benign, the most common being pleomorphic adenomas of the salivary glands and neurogenic tumors. We present a 39-year-old woman who was hospitalized due to left-sided neck pain with a feeling of blockage in the left ear and hearing loss for 10 months. Imaging showed that the mass was not connected to the cranium and the patient underwent surgical resection via a transoral approach, where the contents of the mass were found to be cerebrospinal fluid, and meningocele in the parapharyngeal space is a rare occurrence. The patient presented mainly with painful symptoms, which were eventually relieved by nerve block therapy.

Association of iron deficiency with chronic suppurative otitis media in adults.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a prevalent chronic inflammatory disease globally. Current research suggests a possible association between anaemia and the development of CSOM. OBJECTIVES: The objective of this trial was to investigate the relationship between iron metabolism and chronic suppurative otitis media (CSOM) in adults aged 20-60 years. MATERIALS AND METHODS: A consecutive sampling case-control study was used. The study participants were divided into a case group (42 children diagnosed with CSOM) and a control group (42 children with normal ears). Haemoglobin (Hb), Hematocrit (Hct), mean corpuscular volume of erythrocytes (MCV), serum iron level (SI), unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin (TF), ferritin (Fer) were tested in all the participants, and the results were compared with the normal ranges of the World Health Organization (WHO). The comparative analysis of cases and controls was performed using the Fisher extract test, independence t-test, or Mann-Whitney U test. p-value <.05 was considered statistically significant for correlation. RESULTS: There were 61 patients with CSOM and 61 controls included in the study. In the case group, 16 out of 61 patients (26.2%) had low ferritin levels and in the control group, 1 out of 61 patients (1.6%) had low ferritin levels (p < .001). In the case group, 6 (9.8%) of 61 patients had IDA, and in the control group, there were no patients with IDA among 61 patients (p = .027). There were significant differences in SI, UIBC, and Fer parameters between the groups. CONCLUSIONS: In adult patients, the incidence of iron deficiency was higher in CSOM patients than in controls. Iron deficiency may be considered a potential risk factor for chronic suppurative otitis media, and serum iron parameters should be evaluated in these CSOM patients and further studies should be conducted to better understand the potential link between iron deficiency and CSOM.

Combination of SLC administration and Tregs depletion is an attractive strategy for targeting hepatocellular carcinoma.

BACKGROUND: Secondary lymphoid tissue chemokine (SLC) is a key CC chemokine for chemotaxis of immune cells and has been an attractive candidate for anti-tumor treatments. However, among the immune cells recruited by SLC to tumors, the CD25+ Foxp3+ regulatory T cells (Tregs) compromise the anti-tumor effects. In this study, we proposed the combination therapy of intratumoral co-administration of SLC and anti-CD25 monoclonal antibodies (mAbs). We hypothesized that the intratumoral injections of SLC and depletion of Tregs would have stronger inhibition effects on the progression of hepatocellular carcinoma (HCC) in mice. METHODS: C57BL/6 mice were inoculated subcutaneously with the murine HCC cell line, and mice with visible tumors were treated intratumorally with SLC, SLC plus anti-CD25 mAbs or the control antibodies. The percentages of Tregs, effector CD8+ T cells and CD4+ T cells were checked in the tumors, lymph nodes, spleen and liver at regular intervals. The levels of intratumoral IL-12, IFN-γ, IL-10 and TGF-ß1 were evaluated. The final anti-tumor effects were measured by the tumor volume and weight as well as the intratumoral activity of MMP2 and MMP9. Bone-marrow-derived dendritic cells were used to explore the mechanisms of maturation induced by SLC in vitro. RESULTS: Our experiments showed the combination therapy significantly decreased the frequency of Tregs, and increased CD8+ T cells and CD4+ T cells at tumor sites. These alterations were accompanied by an increased level of IL-12 and IFN-γ, and decreased level of IL-10 and TGF-ß1. Unexpectedly, we observed a significantly decreased percentage of Tregs, and increased CD8+ T cells and CD4+ T cells in the lymph nodes, spleen and liver after the combination therapy. The growth and invasiveness of HCC was also maximally inhibited in the combination therapy compared with the SLC alone. Furthermore, we confirmed SLC induced the maturation of DCs via NF-κB p65 and this maturation would benefit the combination therapy. CONCLUSIONS: Our data demonstrated that intratumoral co-administration of SLC and anti-CD25 mAbs was an effective treatment for HCC, which was correlated with the altered tumor microenvironment and systemically optimized percentages of Tregs, CD8+ T cells and CD4+ T cells in peripheral immune organs.

Development and validation of a machine learning-based predictive model for secondary post-tonsillectomy hemorrhage.

Background: The main obstacle to a patient's recovery following a tonsillectomy is complications, and bleeding is the most frequent culprit. Predicting post-tonsillectomy hemorrhage (PTH) allows for accurate identification of high-risk populations and the implementation of protective measures. Our study aimed to investigate how well machine learning models predict the risk of PTH. Methods: Data were obtained from 520 patients who underwent a tonsillectomy at The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army. The age range of the patients was 2-57 years, and 364 (70%) were male. The prediction models were developed using five machine learning models: decision tree, support vector machine (SVM), extreme gradient boosting (XGBoost), random forest, and logistic regression. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was used to interpret the results of the best-performing model. Results: The frequency of PTH was 11.54% among the 520 patients, with 10.71% in the training group and 13.46% in the validation set. Age, BMI, season, smoking, blood type, INR, combined secretory otitis media, combined adenoidectomy, surgical wound, and use of glucocorticoids were selected by mutual information (MI) method. The XGBoost model had best AUC (0.812) and Brier score (0.152). Decision curve analysis (DCA) showed that the model had a high clinical utility. The SHAP method revealed the top 10 variables of MI according to the importance ranking, and the average of the age was recognized as the most important predictor variable. Conclusion: This study built a PTH risk prediction model using machine learning. The XGBoost model is a tool with potential to facilitate population management strategies for PTH.

Lysophosphatidic acid exerts protective effects on HEI-OC1 cells against cytotoxicity of cisplatin by decreasing apoptosis, excessive autophagy, and accumulation of ROS.

Lysophosphatidic acid (LPA) is an active phospholipid signaling molecule that binds to six specific G protein-coupled receptors (LPA1-6) on the cell surface and exerts a variety of biological functions, including cell migration and proliferation, morphological changes, and anti-apoptosis. The earliest study from our group demonstrated that LPA treatment could restore cochlear F-actin depolymerization induced by noise exposure, reduce hair cell death, and thus protect hearing. However, whether LPA could protect against cisplatin-induced ototoxicity and which receptors play the major role remain unclear. To this end, we integrated the HEI-OC1 mouse cochlear hair cell line and zebrafish model, and found that cisplatin exposure induced a large amount of reactive oxygen species accumulation in HEI-OC1 cells, accompanied by mitochondrial damage, leading to apoptosis and autophagy. LPA treatment significantly attenuated autophagy and apoptosis in HEI-OC1 cells after cisplatin exposure. Further investigation revealed that all LPA receptors except LPA3 were expressed in HEI-OC1 cells, and the mRNA expression level of LPA1 receptor was significantly higher than that of other receptors. When LPA1 receptor was silenced, the protective effect of LPA was reduced and the proportion of apoptosis cells was increased, indicating that LPA-LPA1 plays an important role in protecting HEI-OC1 cells from cisplatin-induced apoptosis. In addition, the behavioral trajectory and in vivo fluorescence imaging results showed that cisplatin exposure caused zebrafish to move more actively, and the movement speed and distance were higher than those of the control and LPA groups, while LPA treatment reduced the movement behavior. Cisplatin caused hair cell death and loss in zebrafish lateral line, and LPA treatment significantly protected against hair cell death and loss. LPA has a protective effect on hair cells in vitro and in vivo against the cytotoxicity of cisplatin, and its mechanism may be related to reducing apoptosis, excessive autophagy and ROS accumulation.

[Relationship between sudden sensorineural hearing loss and facial auditory nerve and anterior inferior cerebellar artery vascular loop in the internal auditory tract MRI].

Objective:To investigate the correlation between the facial auditory nerve and anterior inferior cerebellar artery vascular loop in MRI of the internal auditory meatus and idiopathic sudden sensorineural hearing loss. Methods:This retrospective study enrolled 144 patients with idiopathic sudden sensorineural hearing loss（SSNHL）（experimental group） and 36 healthy subjects with 72 ears（control group）, who attended the Department of Otolaryngology Head and Neck Surgery, the 940th Hospital of the Joint Logistics Support Unit of the Chinese PLA from January, 2019 to January, 2021. The magnetic resonance imaging（MRI） data of the internal auditory meatus and clinical data were collected and compared between the two groups. Results:The distance between the auditory nerve and the peripheral vessels in the unilateral SSNHL-affected ear was significantly different from that in the contralateral ears and that in the healthy ears of the control group （P<0.05）. The distance between the auditory nerve and the peripheral vessels in both ear affected by bilateral SSNHL was significantly different from that in the healthy ears of the control group （P<0.05）. There was no significant difference in radiological grading of vascular loops between the ears affected by unilateral SSNHL and the contralateral ears and the healthy ear of the control group （P>0.05）. No statistically significant differences in radiological grading of vascular loops were found between both ears with bilateral SSNHL and the healthy ears in the control group（P>0.05）. The severity of hearing loss, audiometric configuration, radiological grading of vascular loops and the distance between the facial auditory nerve and peripheral vessels were not significantly different between the affected ears in unilateral SSNHL and both ears in bilateral SSNHL （P>0.05）. Conclusion:SSNHL is associated with the distance between the auditory nerve and the nearest peripheral vessel. SSNHL may occur when the vessel compresses the auditory nerve.

SARS-CoV-2 Spike protein enhances ACE2 expression via facilitating Interferon effects in bronchial epithelium.

OBJECTIVE: In this study, we focused on the interaction between SARS-CoV-2 and host Type I Interferon (IFN) response, so as to identify whether IFN effects could be influenced by the products of SARS-CoV-2. METHODS: All the structural and non-structural proteins of SARS-CoV-2 were transfected and overexpressed in the bronchial epithelial cell line BEAS-2B respectively, and typical antiviral IFN-stimulated gene (ISG) ISG15 expression was detected by qRT-PCR. RNA-seq based transcriptome analysis was performed between control and Spike (S) protein-overexpressed BEAS-2B cells. The expression of ACE2 and IFN effector JAK-STAT signaling activation were detected in control and S protein-overexpressed BEAS-2B cells by qRT-PCR or/and Western blot respectively. The interaction between S protein with STAT1 and STAT2, and the association between JAK1 with downstream STAT1 and STAT2 were measured in BEAS-2B cells by co-immunoprecipitation (co-IP). RESULTS: S protein could activate IFN effects and downstream ISGs expression. By transcriptome analysis, overexpression of S protein induced a set of genes expression, including series of ISGs and the SARS-CoV-2 receptor ACE2. Mechanistically, S protein enhanced the association between the upstream JAK1 and downstream STAT1 and STAT2, so as to promote STAT1 and STAT2 phosphorylation and ACE2 expression. CONCLUSION: SARS-CoV-2 S protein enhances ACE2 expression via facilitating IFN effects, which may help its infection.

Atrial Natriuretic Peptide Promotes Neurite Outgrowth and Survival of Cochlear Spiral Ganglion Neurons in vitro Through NPR-A/cGMP/PKG Signaling.

Sensorineural hearing loss (SNHL) is a dominant public health issue affecting millions of people around the globe, which is correlated with the irreversible deterioration of the hair cells and spiral ganglion neurons (SGNs) within the cochlea. Strategies using bioactive molecules that regulate neurite regeneration and neuronal survival to reestablish connections between auditory epithelium or implanted electrodes and SGN neurites would become attractive therapeutic candidates for SNHL. As an intracellular second messenger, cyclic guanosine-3',5'-monophosphate (cGMP) can be synthesized through activation of particulate guanylate cyclase-coupled natriuretic peptide receptors (NPRs) by natriuretic peptides, which in turn modulates multiple aspects of neuronal functions including neuronal development and neuronal survival. As a cardiac-derived hormone, atrial natriuretic peptide (ANP), and its specific receptors (NPR-A and NPR-C) are broadly expressed in the nervous system where they might be involved in the maintenance of diverse neural functions. Despite former literatures and our reports indicating the existence of ANP and its receptors within the inner ear, particularly in the spiral ganglion, their potential regulatory mechanisms underlying functional properties of auditory neurons are still incompletely understood. Our recently published investigation revealed that ANP could promote the neurite outgrowth of SGNs by activating NPR-A/cGMP/PKG cascade in a dose-dependent manner. In the present research, the influence of ANP and its receptor-mediated downstream signaling pathways on neurite outgrowth, neurite attraction, and neuronal survival of SGNs in vitro was evaluated by employing cultures of organotypic explant and dissociated neuron from postnatal rats. Our data indicated that ANP could support and attract neurite outgrowth of SGNs and possess a high capacity to improve neuronal survival of SGNs against glutamate-induced excitotoxicity by triggering the NPR-A/cGMP/PKG pathway. The neuroregenerative and neuroprotective effects of ANP/NPRA/cGMP/PKG-dependent signaling on SGNs would represent an attractive therapeutic candidate for hearing impairment.

[Research on the correlation between otorhinolaryngologic diseases and environmental meteorological factors in children].

Objective:To explore the correlation between acute otitis media（AOM）, acute pharyngitis（AP） and allergic rhinitis（AR） and environmental-meteorological factors in children in Lanzhou. Method:Data were collected in 2015-2017 from the outpatient department and emergency department of Otolaryngology of one hospital in Lanzhou. The association between clinical data and the environmental meteorological factors during the same period, including the air quality index（AQI）, PM2.5, PM10, CO, NO2, SO2, O3, average temperature, average air pressure, average wind speed, average humidity in Lanzhou, was analyzed. Result:The incidence of AOM was positively correlated with AQI, PM2.5, PM10, CO, NO2, SO2, average air pressure, and was negatively correlated with O3, average wind speed and average air temperature, but not correlated with average humidity. The incidence of AP was positively correlated with average temperature and average humidity, and not correlated with other 9 factors. The incidence of AR was correlated with all 10 environmental meteorological factors except for O3.The number of children with AOM, AP and AR varied with different seasons. Environmental meteorological factors have single lag and cumulative lag effects on the incidence of children with AOM, AP and AR, and difference between the single lag and cumulative lag time was observed. Conclusion:There may be some correlation between the environmental meteorological factors and the incidence of AOM, AP, AR in children, and there is a lag effect. The incidence of pediatric AOM, AP and AR is affected by seasonal factors.

Study on the correlation between ambient environment-meteorological factors and the number of visits of acute otitis media, Lanzhou, China.

To investigate the correlation between environmental-meteorological factors and daily visits for acute otitis media (AOM) in Lanzhou, China. METHODS: Data were collected in 2014-2016 by the Departments of Otolaryngology-Head and Neck Surgery at two hospitals in Lanzhou. Relevant information, including age, sex and visiting time, was collected. Environmental data included air quality index, PM10, PM2.5, O3, CO, NO2 and SO2, and meteorological data included daily average temperature (T, °C), daily mean atmospheric pressure (AP, hPa), daily average relative humidity (RH, %) and daily mean wind speed (W, m/s). The SPSS22.0 software was used to generate Spearman correlation coefficients in descriptive statistical analysis, and the R3.5.0 software was used to calculate relative risk (RR) and to obtain exposure-response curves. The relationship between meteorological-environmental parameters and daily AOM visits was summarized. RESULTS: Correlations were identified between daily AOM visits and CO, O3, SO2, CO, NO2, PM2.5 and PM10 levels. NO2, SO2, CO, AP, RH and T levels significantly correlated with daily AOM visits with a lag exposure-response pattern. The effects of CO, NO2, SO2 and AP on daily AOM visits were significantly stronger compared to other factors (P < 0.01). O3, W, T and RH were negatively correlated with daily AOM visits. The highest RR lagged by 3-4 days. CONCLUSIONS: The number of daily AOM visits appeared to be correlated with short-term exposure to mixed air pollutants and meteorological factors from 2014 through 2016 in Lanzhou.

Effect of c-myc on the ultrastructural structure of cochleae in guinea pigs with noise induced hearing loss.

Noise over-stimulation may induce hair cells loss and hearing deficit. The c-myc oncogene is a major regulator for cell proliferation, growth, and apoptosis. However, the role of this gene in the mammalian cochlea is still unclear. The study was designed to firstly investigate its function under noise condition, from the aspect of cochlear ultrastructural changes. We had established the adenoviral vector of c-myc gene and delivered the adenovirus suspension into the scala tympani of guinea pigs 4 days before noise exposure. The empty adenoviral vectors were injected as control. Then, all subjects were exposed to 4-kHz octave-band noise at 110dB SPL for 8h/day, 3 days consecutively. Auditory thresholds were assessed by auditory brainstem response, prior to and 7 days following noise exposure. On the seventh days after noise exposure, the cochlear sensory epithelia surface was observed microscopically and the cochleae were taken to study the ultrastructural changes. The results indicated that auditory threshold shift after noise exposure was higher in the ears treated with Ad.EGFP than that treated with Ad.c-myc-EGFP. Stereocilia loss and the disarrangement of outer hair cells were observed, with greater changes found in the Ad.EGFP group. Also, the ultrastructure changes were severe in the Ad.EGFP group, but not obvious in the Ad.c-myc-EGFP group. Therefore, c-myc gene might play an unexpected role in hearing functional and morphological protection from acoustic trauma.

The expression of NOB1 in spiral ganglion cells of guinea pig.

OBJECTIVE: NOB1 was a transcription-associated protein, consisting of one zinc ribbon domain. This study aimed to investigate the NOB1 expression in spiral ganglion cells of normal guinea pigs and deaf ones. METHODS: Twelve guinea pigs were randomized equally into experimental group and control group. In experimental group, guinea pigs received a single intramuscular injection of gentamicin, while the control group was treated with physiological saline. Auditory brainstem responses (ABR) test was performed before and 10 days after injection, respectively. Guinea pigs of both groups were sacrificed and temporal bones were removed. The expression of NOB1 in the spiral ganglion was evaluated by immunohistochemistry. RESULTS: NOB1 staining was found expressed in spiral ganglion cells from the basal turn to the apical turn of the cochlea. The expression of NOB1 was found significantly stronger in spiral ganglion cells of deaf guinea pigs as compared with that in normal ones. CONCLUSIONS: The NOB1 was presented in spiral ganglions cells of the guinea pig and might play a role in hearing transduction.

Antitumor immunity by a dendritic cell vaccine encoding secondary lymphoid chemokine and tumor lysate on murine prostate cancer.

AIM: To investigate the antitumor immunity by a dendritic cell (DC) vaccine encoding secondary lymphoid chemokine gene and tumor lysate on murine prostate cancer. METHODS: DC from bone marrow of C57BL/6 were transfected with a plasmid vector expressing secondary lymphoid chemokine (SLC) cDNA by Lipofectamine 2,000 liposome and tumor lysate. Total RNA extracted from SLC+lysate-DC was used to verify the expression of SLC by reverse transcriptase-polymerase chain reaction (RT-PCR). The immunotherapeutic effect of DC vaccine on murine prostate cancer was assessed. RESULTS: We found that in the prostate tumor model of C57BL/6 mice, the administration of SLC+lysate-DC inhibited tumor growth most significantly when compared with SLC-DC, lysate-DC, DC or phosphate buffer solution (PBS) counterparts (P < 0.01). Immunohistochemical fluorescent staining analysis showed the infiltration of more CD4(+), CD8(+) T cell and CD11c(+) DC within established tumor treated by SLC+lysate-DC vaccine than other DC vaccines (P < 0.01). CONCLUSION: DC vaccine encoding secondary lymphoid chemokine and tumor lysate can elicit significant antitumor immunity by infiltration of CD4(+), CD8(+) T cell and DC, which might provide a potential immunotherapy method for prostate cancer.

More than chemotaxis: a new anti-tumor DC vaccine modified by rAAV2-SLC.

Secondary lymphoid tissue chemokine (SLC) is strongly expressed in secondary lymphoid organs. Its ability to facilitate chemotaxis of both dendritic cells (DC) and T cells makes it a promising candidate for cancer therapy. In this study, we modified a BMDC vaccine by incorporating the SLC mature peptide gene. The efficacy of this vaccine was evaluated using a mouse hepatocellular carcinoma (HCC) model, with rAAV2 as the gene delivery vector. The rAAV2 encoding SLC (rAAV2-SLC) transfected immature BMDCs at high efficiency and the anti-tumor effects of SLC gene modified BMDCs (rAAV2-SLC/BMDC) were evaluated. In addition, rAAV2-SLC/BMDC vaccine injected directly into tumors attracted more CD4(+) and CD8(+) T lymphocytes into tumors and showed stronger anti-tumor effects than footpad delivery. Moreover, we found that the phenotypic expression of MHC II, the secretion of IL-12 and IFN-gamma, and T cell stimulation were increased in vitro following treatment with rAAV2-SLC/BMDC vaccine and these responses were inhibited by PTX. In vivo, PTX also inhibited the anti-tumor effects of the vaccine. The results suggest that the expression of SLC by rAAV2-SLC/BMDC plays more than a chemotactic role in anti-tumor responses, thus these studies further demonstrate that SLC has potential to be valuable in cancer therapy.

Postoperation of preauricular fistula cellulitis caused by methicillin-resistant staphylococcus aureus infection.

A one-year-old baby girl with one-month history of recurrent pus fluid exuding from her left preauricular sinus orifice, who failed multiple courses of surgical drainage of the abscess and persistent debridement for the wound, presented with MRSA infection. The patient was treated with linezolid for three days. Her pain and paresthesia resolved, and C-reactive protein decreased to normal.

[Suicidal cancer vaccine enhances anti-tumor immunotherapeutic effect and its safety in the treatment of ovarian cancer].

OBJECTIVE: To study the anti-tumor immunotherapeutic effect induced by the suicidalcancer vaccine FC/TK, and to evaluate the safety of this vaccine. METHODS: The suicidal cancer vaccine, named FC/TK, was prepared by fusion of suicide gene (HSVI,-TK gene) -modified ovarian carcinoma NuTu-19 cells with rat bone marrow-derived dendritic cells (DCs). The morphology of FC/TK was evaluated by scanning electron microscopy. The stimulatory effect of FC/TK on T cells was determined by T cell proliferation assay. In immunotherapeutic studies in vivo, Fischer344 rats were injected subcutaneously with NuTu-19 cells, followed by treatment of FC/TK on days 7 and 14, compared to controls treated with irradiated FC/TK, FC or PBS, respectively. Tumor incidence and volume were measured in 90 days after challenge. To determine the killing effect of FC/TK in vivo, TUNEL assays were applied to detect apoptotic cell death in spleen of vaccinated rats with prodrug ganciclovir administration. RESULTS: FC/TK cells were of irregular shape with surface membrane processes. Compared to the control groups, FC/TK significantly promoted T cell proliferation (P <0.01). The rats vaccinated with FC/TK and FC significantly inhibited the tumor growth compared to rats vaccinated with irradiated FC/TK (P <0.05) or with PBS ( P <0.01). The immunotherapeutic effect induced by FC/TK was similar to that using FC. Fluorescence microscopy showed that fluorescein-stained FC/TK cells migrated into spleen also showed to be TUNEL-positive, suggesting that the FC/TK cells were killed by ganciclovir in vivo. CONCLUSION: Our data indicate that suicidal cancer vaccine is an effective and safe therapy for ovarian carcinoma and may serve as a broadly applicable approach for other cancer vaccines in the future.

[Effects and mechanism of hyperglycemia on development and maturation and immune function of human monocyte derived dendritic cells].

OBJECTIVE: Dendritic cells play an important role in the pathogenesis of atherosclerosis. To explore the effects of hyperglycemia on the maturation and immune function of human monocyte derived dendritic cells (MDCs). METHODS: Immature MDCs were cultured in RPMI1640 medium with either 5.5 mmol/L D-glucose (NG), 25 mmol/L D-glucose (HG) or 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol (HM) in the absence or presence of 30 mmol/L N-acetylcysteine [NAC, a reactive oxygen species inhibitor (ROS)] for 48 hours. FACS was used to investigate the MDCs immunophenotypic expression. Immune function was evaluated by allogeneic mixed T lymphocyte reaction and measurement of cytokine levels from culture supernatants. Intracellular ROS production in MDCs was also measured by 2', 7'-dichlorodihydrofluorescein (DCF, 10 micromol/L) fluorescence using confocal laser-scanning microscopy techniques. RESULTS: Compared with NG and HM treated MDCs, the expression of maturation markers such as CD1a, HLA-DR, CD83, CD86 were significantly upregulated, allogeneic T cells proliferation as well as the cytokines secretions (IL-2, IL-12, IL-10 and IFN-gamma) significantly increased in HG treated MDCs. Intracellular ROS production in MDCs was also significantly increased and all these stimulatory effects of HG could be partially attenuated by NAC. CONCLUSION: High glucose promote the maturation of MDCs and augment their capacity to stimulate T-cell proliferation and cytokine secretions at least in part through enhancing intracellular ROS generation. These stimulating effects of high glucose on MDCs maturation may be one of the mechanisms of accelerated atherosclerosis found in patients with diabetes.