[Potential therapeutic effect of Saussureae Involucratae Herba on breast cancer and its mechanism based on network pharmacology].

As one of the most commonly diagnosed cancers in the world, female breast cancer is induced by the high level of estrogen. Saussureae Involucratae Herba(SIH), a gynecological medicinal, regulates estrogen-induced diseases. However, the therapeutic effect of SIH on breast cancer has not been reported. Therefore, this study aims to explore the potential efficacy of SIH on breast cancer based on in vitro experiment and network pharmacology. The inhibitory effect of SIH water extract on proliferation and migration of breast cancer MDA-MB-231 cells was examined. The result demonstrated SIH water extract significantly suppressed the proliferation of breast cancer cells(IC_(50)=6.47 mg·mL~(-1)) and also restricted the migration. A total of 39 components of SIH were retrieved from traditional Chinese medicine database(TCMD) and 160 targets of SIH were screened by target fishing with the PharmaDB database. The Online Mendelian Inheritance in Man(OMIM) was used to establish a 1 001-targets data set of breast cancer. Based on the overlaps(45) of targets between SIH and breast cancer, a protein-protein interaction(PPI) network was built to analyze the interactions among these targets with STRING platform and Cytoscape. Finally, through topology and GO and KEGG analysis, 8 targets, 101 pathways and 85 biological processes were found to involve the treatment of breast cancer by SIH. SIH may exert the anti-breast cancer effect by regulating cell cycle, inhibiting proliferation, migration and adhesion of cancer cells, and modulating estrogen receptor. This study clarified the mechanism of SIH in treating breast cancer, which lays a foundation for the further development of SIH.

Recurrent granular cell tumor of the thyroid: a case report and literature review.

BACKGROUND: Granular cell tumor (GCT) of the thyroid is a rare benign tumor of Schwann cell origin with a favorable prognosis and only 10 cases have been reported so far in scientific literature. The present case study describes the first case of recurrent thyroid GCT. CASE PRESENTATION: Our case describes a 20-year-old woman who had undergone lobectomy for GCT of the thyroid 4 years ago. Hematoxylin-eosin (HE) staining revealed that the lesion was composed of epithelioid cells with an abundance of eosinophilic granular cytoplasm. Immunohistochemical analysis showed that tumor cells tested positive for S-100 protein and negative for desmin. Both histological and immunohistochemical analyses supported the diagnosis of recurrent GCT of the thyroid. CONCLUSIONS: Our case suggested that a tumor-free margin excision and post-operative follow-up are necessary for the treatment of GCT of the thyroid.

Safety and complications of medical thoracoscopy in the management of pleural diseases.

BACKGROUND: Medical thoracoscopy is considered an overall safe procedure, whereas numbers of studies focus on complications of diagnostic thoracoscopy and talc poudrage pleurodesis. We conduct this study to evaluate the safety of medical thoracoscopy in the management of pleural diseases and to compare complications in different therapeutic thoracoscopic procedures. METHODS: A retrospective study was performed in 1926 patients, 662 of whom underwent medical thoracoscopy for diagnosis and 1264 of whom for therapeutic interventions of pleural diseases. Data on complications were obtained from the patients, notes on computer system, laboratory and radiographic findings. Chi-square test was performed to compare categorical variables and Fisher's exact test was used for small samples. RESULTS: The mean age was 51 ± 8.4 (range 21-86) years and 1117 (58%) were males. Diagnostic procedure was taken in 662 (34.4%) patients, whereas therapeutic procedure was taken in 1264 (65.6%) patients. Malignant histology was reported in 860 (44.6%) and 986 (51.2%) revealed benign pleural diseases. Eighty patients (4.2%) were not definitely diagnosed and they were considered as unidentified pleural effusion. One patient died during the creation of artificial pneumothorax, and the causes of death were supposed as air embolism or an inhibition of phrenic motoneurons and circulatory system. Complication of lung laceration was found in six patients (0.3%) and reexpansion pulmonary edema was observed in two patients (0.1%). Higher incidence of prolonged air leak was observed in bulla electrocoagulation group, in comparison with pleurodesis group. Moreover, pain and fever were the most frequently complications in pleurodesis group and cutaneous infection in entry site was the most frequently reported complication in pleural decortication of empyema group. CONCLUSIONS: Medical thoracoscopy is generally a safe and effective method, not only in the diagnosis of undiagnosed pleural effusions, but also in the management of pleural diseases. Mastering medical thoracoscopy well, improving patient management after the procedure and attempts to reduce the occurrence of post-procedural complications are the targets that physicians are supposed to achieve in the future.

An Experimental Study on the Optimal Timing for the Repair of Incomplete Facial Paralysis by Hypoglossal-facial 'Side'-to-side Neurorrhaphy in Rats.

OBJECTIVE: To investigate the optimal timing for the repair of persistent incomplete facial paralysis by hypoglossal-facial 'side'-to-side neurorrhaphy in rats. METHODS: A total of 30 adult rats with crushed and bulldog-clamped facial nerve injury were randomly divided into 5 groups (n = 6 each) that were subjected to injury without nerve repair or with immediate repair, 2-week-delayed repair, 4-week-delayed repair, or 8-week-delayed repair. Three months later, the effects of repair in each rat were evaluated by facial symmetry assessment, electrophysiological examination, retrograde labeling, and axon regeneration measurement. RESULTS: At 3 months after injury, the alpha angle significantly increased in the group of rats with 4-week-delayed repair compared with the other four groups. Upon stimulation of the facial nerve or Pre degenerated nerve, the muscle action potentials MAPs were recorded in the whisker pad muscle, and the MAP amplitude and area under the curve in the 4-week-delayed repair group were significantly augmented at 3 months post-injury. Similarly, the number of retrograde-labeled motor neurons in the facial and hypoglossal nuclei was quantified to be significantly greater in the 4-week-delayed repair group than in the other groups, and a large number of regenerated axons was also observed. CONCLUSION: The results of this study demonstrated that hemiHN-FN neurorrhaphy performed 4 weeks after facial nerve injury was most effective in terms of the functional recovery of axonal regeneration and activation of facial muscles.

Free perforator flap transfer for reconstruction of skull base defects after resection of advanced recurrent tumor.

BACKGROUND: Skull base reconstruction is challenging due to its proximity to important anatomical structures. This report evaluates the use of perforator flaps for reconstruction of skull base defects after advanced recurrent tumor resection. METHODS: Fourteen free perforator flaps were transferred to reconstruct skull base defects in 14 consecutive patients, from October 2004 to May 2011. All patients had advanced recurrent neoplasms that were previously treated with either radiation therapy or surgery. The surgical defects were reconstructed using various perforator flaps mainly the deep inferior epigastric artery perforator flaps, anterolateral thigh (ALT) flaps, or thoracodorsal artery perforator flaps. The outcomes following reconstruction and associated complications were evaluated. RESULTS: The overall free flap success rate was 93% (13/14). One ALT flap was lost. Three patients (20%) had a cerebrospinal fluid fistula, and two of them developed meningitis. No complications were observed at the donor site. CONCLUSIONS: The use of perforator flaps may be a viable option for reconstruction of skull base defects after the resection of advanced recurrent tumor.

The role of intestinal microbiota and metabolites in intestinal inflammation.

With the imbalance of intestinal microbiota, the body will then face an inflammatory response, which has serious implications for human health. Bodily allergies, injury or pathogens infections can trigger or promote inflammation and alter the intestinal environment. Meanwhile, excessive changes in the intestinal environment cause the imbalance of microbial homeostasis, which leads to the proliferation and colonization of opportunistic pathogens, invasion of the body's immune system, and the intensification of inflammation. Some natural compounds and gut microbiota and metabolites can reduce inflammation; however, the details of how they interact with the gut immune system and reduce the gut inflammatory response still need to be fully understood. The review focuses on inflammation and intestinal microbiota imbalance caused by pathogens. The body reacts differently to different types of pathogenic bacteria, and the ingestion of pathogens leads to inflamed gastrointestinal tract disorders or intestinal inflammation. In this paper, unraveling the interactions between the inflammation, pathogenic bacteria, and intestinal microbiota based on inflammation caused by several common pathogens. Finally, we summarize the effects of intestinal metabolites and natural anti-inflammatory substances on inflammation to provide help for related research of intestinal inflammation caused by pathogenic bacteria.

Comparison of the Nerve Regeneration Capacity and Characteristics between Sciatic Nerve Crush and Transection Injury Models in Rats.

Objective: To provide useful information for selecting the most appropriate peripheral nerve injury model for different research purposes in nerve injury and repair studies, and to compare nerve regeneration capacity and characteristics between them. Methods: Sixty adult SD rats were randomly divided into two groups and underwent crush injury alone (group A, n = 30) or transection injury followed by surgical repair (group B, n = 30) of the right hind paw. Each group was subjected to the CatWalk test, gastrocnemius muscle evaluation, pain threshold measurement, electrophysiological examination, retrograde neuronal labeling, and quantification of nerve regeneration before and 7, 14, 21, and 28 days after injury. Results: Gait analysis showed that the recovery speed in group A was significantly faster than that in group B at 14 days. At 21 days, the compound muscle action potential of the gastrocnemius muscle in group A was significantly higher than that in group B, and the number of labeled motor neurons in group B was lower than that in group A. The number of new myelin sheaths and the g-ratio were higher in group A than in group B. There was a 7-day time difference in the regeneration rate between the two injury groups. Conclusion: The regeneration of nerve fibers was rapid after crush nerve injury, whereas the transection injury was relatively slow, which provides some ideas for the selection of clinical research models.

MicroRNA-139-5p negatively regulates NME1 expression in hepatocellular carcinoma cells.

BACKGROUND: High expression of NME1 is associated with hepatocellular carcinoma (HCC) progression and poor prognosis. However, there are few reports on the association between NME1 and microRNAs (miRNAs) in HCC progression. OBJECTIVES: To explore miRNAs that regulate NME1 expression in HCC. MATERIAL AND METHODS: Data from the Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), TargetScan, starBase, and mirDIP were used to analyze the expression pattern of NME1 in HCC tissues, the relationship between NME1 level and the progression of HCC or patient prognosis, miRNAs targeting NME1, and the biological processes that may be regulated by NME1. The regulation of miRNAs to NME1 was assessed using the dual-luciferase reporter assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. The cell cycle and cell proliferation were detected using propidium iodide (PI) staining and EdU assay, respectively. RESULTS: Highly expressed NME1 in HCC was associated with HCC progression and prognosis. The miR-139-5p and miR-335-5p were weakly expressed in HCC samples and negatively correlated with NME1. The downregulation of miR-139-5p in HCC patients resulted in worse overall survival (OS) and disease-free interval (DFI); however, the level of miR-335-5p was not significantly correlated with OS and DFI in patients with HCC. In vitro experiments verified that the level of miR-139-5p was lower and NME1 expression was higher in HCC cell lines compared to L-02. Moreover, miR-139-5p negatively regulates the expression of NME1 in HCC cell lines. The NME1 may regulate cell cycle, DNA replication, oxidative phosphorylation, and the pentose phosphate pathway. The miR-139-5p inhibited cell proliferation by negatively regulating NME1 expression. CONCLUSIONS: The upregulation of NME1 in HCC indicates a poor prognosis. The NME1 is negatively regulated by miR-139-5p to inhibit cell proliferation.

Free Flap Transfer, a Safe and Efficient Method for Reconstruction of Composite Skull Base Defects After Salvage Resection of Advanced Intracranial and Extracranial Communicating Tumors.

OBJECTIVE: Surgical treatment of advanced intracranial and extracranial communicating skull base tumors is challenging, especially for the reconstruction of the large composite defect left by tumor resection. The aim of the study is to evaluate the utility of the free flap reconstruction of the defects resulting from radical resection of these tumors in a single institution. METHODS: The clinical data of 17 consecutive patients who underwent free flap reconstruction for defect left by salvage resection of advanced intracranial and extracranial communicating tumors from 2013 to 2019 were retrospectively collected and analyzed. RESULTS: There were 5 squamous cell carcinomas, 4 adenoid cystic carcinomas, 2 basal cell carcinomas, 2 meningiomas, 1 anaplastic hemangiopericytoma, 1 pleomorphic adenoma, 1 osteosarcoma, and 1 chondrosarcoma. All patients had recurrent neoplasms, 2 of whom had pulmonary metastasis. A modified radical cervical dissection was performed in 6 patients. The anterolateral thigh myocutaneous flap and rectus abdominis myocutaneous flap were used in 15 patients (88.2%) and 2 patients (11.8%), respectively. Complications were seen in 3 of 17 patients (17.6%) with 1 total flap loss. The median progression-free survival duration was 31 months. The 3- and 5-year progression-free survival rates were 0.47 and 0.24, respectively. The mean overall survival duration was 66 months. The 3- and 5-year overall survival rates were 0.85 and 0.68, respectively. CONCLUSIONS: Free flap transfer is a safe and effective method with acceptable complications, useful for reconstruction of large composite skull base defects after salvage resection of advanced intracranial and extracranial communicating tumors. The functional and cosmetic results are satisfying.

The Effect of A2E on the Uptake and Release of Calcium in the Lysosomes and Mitochondria of Human RPE Cells Exposed to Blue Light.

We aimed to explore the effect of N-retinylidene-N-retinylethanolamine (A2E) on the uptake and release of calcium in lysosomes and mitochondria by establishing a model of human retinal pigment epithelial (RPE) cell injury induced by exposure to blue light. Primary human RPE cells were cultured from passages 4 to 6 and exposed to blue light at an intensity of 2000 ± 500 lux for 6 hours. After blue light exposure, the culture was maintained for 24 hours. A2E at a final concentration of 25 µM was added to the culture 2 hours before light exposure, and nifedipine at a final concentration of 10-4 M was added 1 hour before light exposure. The levels of Ca2+ in the cytosol (CaTM/2AM), mitochondria (Rhod/2AM), and lysosomes (LysoTracker Red and Fluo-3/AM) were determined. In order to measure the calcium levels in the different organelles, RPE were imaged using a laser scanning confocal microscope. Moreover, changes in the mitochondrial membrane potential were detected by flow cytometry analysis of JC-1-stained cells. The obtained results revealed that blue light illumination increased the calcium fluorescence intensity in the cytoplasm, mitochondria, and lysosomes of human RPE cells when compared with the control cells (P < 0.05). After A2E treatment, the fluorescence intensity of the calcium in the cytoplasm was further increased (P < 0.05), while that in the mitochondria and lysosomes decreased (P < 0.05). In addition, we observed that nifedipine reduced the fluorescence intensity of calcium in the RPE cells. Our results also showed that the mitochondrial membrane potential in the RPE treated with blue light and A2E was lower than that in the control, blue light, and A2E-treated cells (P < 0.05). Blue light increased calcium levels in the cytoplasm, lysosomes, and mitochondria of RPE cells. A2E damages the lysosomal and mitochondrial membranes, resulting in calcium release into the cytoplasm. Finally, our results demonstrated that both blue light and A2E treatments reduced mitochondrial membrane potential, increasing cytosolic Ca2+ levels, which can contribute to the activation of RPE death.

[Atypical pathogens in adult patients admitted with community-acquired pneumonia].

OBJECTIVE: To investigate the current status of atypical pathogen associated infections in community-acquired pneumonia (CAP) in adults, and their clinical attributes. METHODS: Clinical data, sputum specimens from acute phase, and paired sera from acute- and convalescent-phases of CAP in 153 adult patients were collected from May 2005 to May 2008 in multiple medical centers. Chlamydia pneumoniae (Cpn) IgG antibody, and Legionella pneumophila (LP) mixed IgG, IgA and IgM antibodies were determined by indirect immuno-fluorescent assay. Mycoplasma pneumoniae (Mpn) mixed IgG, IgA and IgM antibodies were determined by passive agglutination assay. All the sputum specimens were routinely cultured for bacterial isolation. RESULTS: Fifty-two (34%) out of the 153 cases were diagnosed as atypical CAP per the paired serum-antibody assay. Forty-seven of the 52 atypical CAP cases were infected by one atypical pathogen, 38 with Cpn, 4 with Mpn, and 5 with LP, while 5 out of the 52 atypical CAP cases were infected by 2 pathogens, Cpn and Mpnin 2, Cpn and LP in 3 cases. Eleven cases (21.2%) out of the 52 patients with atypical pneumonia were complicated with bacterial infection. Except peripheral white blood count was significant increased in the group of typical (bacterial only) pneumonia (WBC > 10 × 109)/L, P = 0.03), all the other clinical parameters did not show statistically significant difference between the typical and the atypical pneumonia groups. CONCLUSIONS: Our data suggest that Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila are common pathogens of adult CAP. Chlamydia pneumoniae might be the most frequent atypical pathogen associated with atypical CAP.

Analysis of Preoperative Factors Influencing Hypoglossal-facial 'Side'-to-side Neurorrhaphy for Facial Paralysis after Excision of Acoustic Neuroma.

OBJECTIVE: Hypoglossal nerve-facial nerve 'side'-to-side neurorrhaphy is a new method for the treatment of potential incomplete facial paralysis after acoustic neuroma. However, there are differences in postoperative outcomes among patients. This study analysed preoperative factors that may influence the treatment outcomes of neurorrhaphy. METHODS: We performed a retrospective study of 53 patients who were treated by neurorrhaphy for facial paralysis after acoustic neuroma resection. After a one-year follow-up period, the patients were divided into two groups according to facial functional outcome: better recovery or ordinary recovery. We analysed the following factors: gender, age, tumour size, and characteristics, tumour adhesion to the facial nerve, the duration of facial paralysis (DFP) and F wave appearance prior to neurorrhaphy (F wave). RESULTS: Univariate analysis showed significant differences between the two groups in DFP ( P = 0.0002), tumour adhesion to the facial nerve ( P = 0.0079) and F waves ( P = 0.0048). Logistic regression analysis of these factors also showed statistical significance with P values of 0.042 for the DFP, 0.043 for F waves, and 0.031 for tumour adhesion to the facial nerve. CONCLUSIONS: Tumour adhesion to the facial nerve, F waves appearance and DFP prior to neurorrhaphy are the predominant factors that influence treatment outcomes.

Clinical efficacy of treatment for primary tracheal tumors by flexible bronchoscopy: Airway stenosis recanalization and quality of life.

The aim of the present study was to evaluate the effectiveness of interventional treatment of primary tracheal tumors through flexible bronchoscopy. The clinical data of 38 patients with primary tracheal tumours who underwent flexible bronchoscopy intervention therapy between January 2011 and January 2017 were retrospectively analyzed. The average time interval from onset of symptoms to the appearance of actual clinical manifestations in the 38 patients ranged from 0 to 60 months, with an average of 8.1±11.6 months and a median of 4.2 months. The rate of misdiagnosis at the first visit was 36.8% (14/38). After interventional treatment, the overall efficiency (complete + partial response) of airway stenosis recanalization in the 38 patients was 89.5%. In 3 patients with benign tumors, the anhelation score was reduced following treatment (1.00±0.77 vs. 3.13±1.21 at the pre-treatment stage; P<0.001). The overall survival rates of the 35 patients at 1, 3 and 5 years were 69.3, 48.7 and 20.3%, respectively. Therefore, flexible bronchoscopic intervention may effectively smoothen the airways of patients and relieve the symptoms of anhelation. Combining radiotherapy and chemotherapy may improve patient prognosis and safety.

N-terminal α-amino group modification of antibodies using a site-selective click chemistry method.

Site-specific conjugation of small molecules to antibody molecules is a promising strategy for generation of antibody-drug conjugates. In this report, we describe the successful synthesis of a novel bifunctional molecule, 6-(azidomethyl)-2-pyridinecarboxyaldehyde (6-AM-2-PCA), which was used for conjugation of small molecules to peptides and antibodies. We demonstrated that 6-AM-2-PCA selectively reacted with N-terminal amino groups of peptides and antibodies. In addition, the azide group of 6-AM-2-PCA enabled copper-free click chemistry coupling with dibenzocyclooctyne-containing reagents. Bifunctional 6-AM-2-PCA mediated site-specific conjugation without requiring genetic engineering of peptides or antibodies. A key advantage of 6-AM-2-PCA as a conjugation reagent is its ability to modify proteins in a single step under physiological conditions that are sufficiently moderate to retain protein function. Therefore, this new click chemistry-based method could be a useful complement to other conjugation methods.

[Research about schwann cells and PLGA implanted to rat transected spinal cord].

OBJECTIVE: To investigate the recovery of rat transected spinal cord injury after implantation of Schwann cells combined with poly (lactide-co-glycolide) (PLGA). METHODS: Schwann cells were expanded, co-cultured with PLGA for 9 days in vitro, and then analyzed with scanning electron microscope (SEM). Rat spinal cord at the level of T(9) was transected. Schwann cells labeled with BrdU and PLGA scaffold were implanted to injury site. After 1, 3, 6 months, BrdU/MBP immunohistochemistry double staining, semi-thin sections stained thionin and ultra-thin section were performed to investigate myelin renew. BBB open field locomotion, motor evoked potential (MEP), compound muscle action potential (CMAP) and somatosensory evoked potential (SEP) were recorded. RESULTS: Schwann cells grew well on PLGA under SEM. BrdU/MBP double positive cells would been seen, remyelination was thin and formed by Schwann cells at 6 months later under electron microscope (EM). BBB behavioral tests revealed no significant difference in recovery comparing with experiment group and control group. The results of MEP, CMAP and SEP showed no significant improvement in the conduction of spinal cord. CONCLUSIONS: There are the compatibility between Schwann cells and PLGA. Although remyelination was found in morphology, function conduction of spinal cord failed to be established.

The Changes of Th17/Treg and Related Cytokines: IL-17, IL-23, IL-10, and TGF-ß in Respiratory Syncytial Virus Bronchiolitis Rat Model.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization that lead to high morbidity and mortality among young infants. T helper 17 (Th17) cells and regulatory T cells (Tregs) play essential roles in the pathogenesis of autoimmune, cancer, and inflammatory diseases. However, whether changes in T-cell subsets are related to the systemic immune responses in RSV-caused bronchiolitis merit further investigation. Three-week-old Sprague Dawley (SD) rats were randomly divided into the normal control (NC) and RSV bronchiolitis (RSV-B) groups. An RSV-B model was successfully established using nasal drip containing RSV. Furthermore, pathological changes in the lung tissues were observed using hematoxylin and eosin staining. Flow cytometry determined the levels of Th17 and Treg subsets. The related cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of related transcription factors, such as RORγt and FOXP3, were examined using real-time quantitative PCR and western blot analysis. The RSV-B group exhibited pulmonary interstitial hyperemia and edema, inflammatory cell infiltration, wide alveolar septa, and bronchial collapse and deformation. The percentage of Th17 cells in RSV-B group was about 2.3 fold higher than that of NC group, and the concentration of IL-17, IL-23 and RORγt was higher than in NC group. In contrast, the percentage of Treg cells in the RSV-B group was approximately 0.7 fold lower than that in the NC group, and the levels of IL-10, TGF-ß, and FOXP3 in the RSV-B group were lower than those in the NC group. The above results were statistically significant. The changes of Th17/Treg, and their associated cytokines, specific transcription factors, are present in RSV bronchiolitis model rats, which may play an important role in the pathogenesis of RSV bronchiolitis.

Noninvasive Imaging of Ras Activity by Monomolecular Biosensor Based on Split-Luciferase Complementary Assay.

Deregulated activity of Ras GTPases has been observed in many types of human cancers, and contributes to the diverse aspects of carcinogenesis. Although the significance in tumorigenesis has been widely accepted and many therapeutic drugs are under development, little attention has been dedicated to the development of sensors for the Ras activity in vivo. Therefore, based on the split firefly luciferase complementation strategy, we developed a monomolecular bioluminescent biosensor to image endogenous Ras activity in living subject. In this biosensor, two inactive luciferase fragments are sandwiched by Raf-1, whose conformation changes upon GTP-Ras binding. Thus, the Ras activity can be surrogated by the intensity of the complementary luciferase. The bioluminescence analyses demonstrated that this novel biosensor behaved the robust and sensitive reporting efficiency in response to the dynamical changes of Ras activity, both in living colorectal cancer cells and in vivo. Compared to the traditional method, such as the pull-down assay, the bioluminescent sensor is simply, noninvasive, faster and more sensitive for the analysis of the endogenous Ras activity. This innovative work opens up the way for monitoring the preclinical curative effect and high-throughput screening of therapeutic drugs targeting Ras pathways.

Correlation between DNA repair capacity in lymphocytes and acute side effects to skin during radiotherapy in nasopharyngeal cancer patients.

PURPOSE: Repair of radiation-induced DNA damage plays a critical role for both the susceptibility of patients to side effects after radiotherapy and their subsequent cancer risk. The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy. EXPERIMENTAL DESIGN: Nasopharyngeal cancer patients receiving radiation therapy were recruited in a prospective epidemiologic study. As an indicator for clinical radiosensitivity, adverse reactions of the skin were recorded. Cryopreserved lymphocytes from 100 study participants were gamma-irradiated with 5 Gy in vitro and analyzed using the alkaline comet assay. Reproducibility of the assay was determined by repeated analysis (n = 22) of cells from a healthy donor. A coefficient of variation of 0.24 was calculated. RESULTS: The various parameters determined to characterize the individual DNA repair capacity showed large differences between patients. Twenty-one patients were identified with considerably enhanced DNA damage induction, and 19 patients exhibited severely reduced DNA repair capacity after 15 and 30 minutes. Eight patients were considered as clinically radiosensitive, indicated by moist desquamation of the skin after a total radiation dose of 70 Gy. CONCLUSIONS: Using the alkaline comet assay as described here, nasopharyngeal cancer patients were identified showing abnormal cellular radiation effects, but this repair deficiency corresponded only at a very limited extent to the acute radiation sensitivity of the skin.

Protective effect of isoflurane and sevoflurane on ischemic neurons and expression of Bcl-2 and ICE genes in rat brain.

OBJECTIVE: To study the protective effect of volatile anesthetics, isoflurane and sevoflurane, on ischemic neurons after cerebral ischemia-reperfusion in rats and its possible molecular mechanism. METHODS: Rat cerebral ischemia-reperfusion model was developed by occlusion of the middle cerebral artery (MCA) and bilateral common carotid arteries (CCAs) 1 h after reperfusion. Using flow cytometry (FCM) and Northern blot hybridization, we calculated the number of apoptotic bodies and detected the expression of bcl-2 mRNA and interleukin-1beta converting enzyme (ICE) mRNA. RESULTS: The apoptotic bodies in hippocampus analyzed by FCM peaked at appeared 24 h after reperfusion, and decreased about 54% and 40%, respectively, after treatment with isoflurane and sevoflurane, as compared with ischemic group. There was no significant difference in the expression of bcl-2 mRNA and ICE mRNA between the inhaled anesthetic groups and ischemic group in hippocampus 24 h after MCA/CCAs occlusion. CONCLUSION: Isoflurane and sevoflurane partially inhibit apoptosis but have no significant effect on the expression of bcl-2 and ICE genes.

[Prospective cohort study on prevention of Frey syndrome in parotid surgery].

OBJECTIVE: To investigate the prevention of Frey syndrome after parotidectomy. METHODS: A prospective cohort study of 100 patients with parotid cancer who received parotid surgery was underwent in our hospital from 2001 to 2004. These patients were assigned to two groups, study group (50 cases) and control group (50 cases). The patients in the study group received parotidectomy and intraoperative placement of collagen pieces within the parotid bed, between the skin flap and the facial nerve. The patients in the control group received a conventional parotidectomy and no collagen pieces was implanted. All of the patients were followed-up and were evaluated for Frey syndrome with identical questionnaires. RESULTS: Compared with control group, the incidence rate of Frey syndrome was significantly decreased in the study group (20% vs 60%, chi(2) = 15.04, P < 0.001). Postoperative incidence of facial contour apparent deformity was 80% (40/50) in control group and 44% (22/50) in study group (chi(2) = 12.26, P < 0.001). CONCLUSIONS: Use of collagen pieces as an interposition fill barrier improves parotidectomy outcome by reducing the incidence of Frey syndrome, and it improves cosmetic results concurrently.