Oral mucosal drug delivery has the advantages of rapid drug absorption, no first-pass effect and good patient compliance. However, factors such as low drug dissolution, saliva carrying the drug into the gastrointestinal tract and the existence of physiological barriers in the mucosa may affect the mucosal permeation and bioavailability of the drug. Nanotechnology applied to drug oral mucosa delivery can overcome the above disadvantages and obtain efficient absorption effect. This paper describes the physiological structure of oral mucosa and the factors affecting the absorption of drugs in oral mucosa, reviews the application of nanotechnology such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, polymer nanoparticles, polymer micelles and nanohybrid suspensions in oral mucosal drug delivery and the mechanism of promoting drug absorption, summarizes the main problems of current research, and gives an outlook on the application of nano oral mucosal drug delivery system. The main problems of current research are summarized, and the prospects for the application of nano oral mucosal drug delivery systems are discussed.

OBJECTIVETo estimate the size of female sex workers and clients in Taizhou city.

METHODSA household survey using network scale-up method (NSUM) was conducted among the 3000 community residents in Taizhou city from August to October in 2011, which aimed to estimate the social network size (c value) of Taizhou residents, and the c value was adjusted by demographic characteristics, back estimation and outlier elimination. Using the adjusted c value, the number of acquaintance of female sex workers or clients and the respect level toward female sex workers or clients were used to estimate the size of female sex workers and clients.

RESULTSA total of 2783 valid questionnaires were collected, among which 1380 (49.6%) were collected from Taixing city, 1403 (50.4%) were collected from Jingjiang city. 1334 respondents were male (47.9%) and 1449 (47.9%) respondents were female. The mean age was (39.4 ± 10.7) years. The average personal social network size using original data for Taizhou residents was 525, which differed from place, sex, age, educational level and marriage status. Using the remaining known populations through back estimation, the social network size was 419 and became 424 after the elimination of outliers. The estimated population size for female sex worker was 6370 (95%CI: 5886 - 6853), which accounted for 0.52% (6370/1 229 980) of the total number of female aged from 15 to 49. The estimated population size for clients was 15 202 (95%CI: 14 560 - 15 847), which accounted for 1.28% (15 202/1 190 340) of the total number of males aged from 15 to 49 and the ration of clients to female sex worker was 2.39:1.

CONCLUSIONNSUM is an easy and quick way to estimate the size of female sex workers or clients, but the estimated sizes are subject to bias and error due to estimate effect and sample representativeness.

Adolescent ; Adult ; China ; Female ; Humans ; Male ; Middle Aged ; Sex Work ; statistics & numerical data ; Sex Workers ; statistics & numerical data ; Surveys and Questionnaires ; Young Adult

Objective To analyze the imaging and pathological characteristics, as well as treatment strategies of intracranial hemangioblastomas (HBs),and explore the advancement of diagnosis,etiopathogenisis and treatment of HBs. Methods Thirty-five patients with intracranial HBs,admitted to our hospital and performed tumor resection from January 2005 to January 2010,were chosen in our study; all patients were divided into type of big cystic HBs with a small mural nodule (n=19),type of small cystic HBs with a big nodule (n=9) and type of solid HBs (n=7) by imaging features.The clinical manifestations,imaging findings and surgical methods were retrospectively analyzed; the expressions of NSE and CD34 in these tumor samples were detected by HE staining and immunohistochemical staining.Results All patients were treated by surgery; total resection was achieved in 34 and subtotal resection in 1; no death occurred after the surgery.Twenty-eight patients were followed up for 3 months to 3 years after discharge; recurrence appeared in 1 patient with big cystic HBs with a small mural nodule and Gamma knife treatment was performed.No significant difference was observed in the numbers ofCD34+cells between each 2 types of patients (P＞0.05).The numbers of NSE positive cells between each 2 types were statistically significant (P＜0.05). Conclusion There were no specific clinical manifestations of HBs.Diagnosis was mainly according to imaging features.Treatment of HBs with total resection is just the first selection and the key to reduce palindromia; the formation of HBs cysts is closely related to tumor stromal cells.

OBJECTIVETo construct a recombinant adenovirus vector expressing TbetaR-II extracellular domain-RANTES fusion gene and evaluate its anti-tumor effects.

METHODSMouse origin TbetaR-II extracellular domain and RANTES gene were amplified by RT-PCR. The TbetaR-II extracellular domain-RANTES fusion gene was amplified by overlapping PCR method. TbetaR-II extracellular domain-RANTES fusion gene was cloned into pDC316 vector. The recombinant adenovirus vector expressing the fusion gene was constructed by adMax adenovirus vector creation system. Recombinant adenovirus vector expressing the fusion gene was transfected into LA795 cells. The expression of recombinant adenovirus was checked by Westen blot. The levels of TGF-beta1, RANTES in supernatant were checked by ELISA. The transfected cells were counted and growth curve was obtained. Apoptosis of transfected cells was detected by Annexin V FITC method. The chemotactic activity of supernatant of transfected cells to splenic lymphocytes was assayed. Transfected cells (1 x 10(5)) were inoculated into T739 mice and to observe the tumor growth and survival time. Ad-TbetaR-II extracellular domain, Ad-RANTES and Ad-TbetaR-II extracellular domain-RANTES fusion gene(1 x 10(10) pfu) were injected into the tumor in T739 mice. The tumor size and tumor weight were recorded and tumor growth inhibition rate was counted and statistically analyzed.

RESULTSTbetaR-II extracellular domain and RANTES gene were amplified by RT-PCR and TbetaR-II extracellular domain-RANTES fusion gene amplified by overlapping PCR, were identified by DNA sequence analysis. Restriction enzyme digestion analysis showed that the recombinant vector was constructed correctly. The recombinant adenovirus vector expressing the fusion gene was constructed successfully using the AdMax Adenovirus Vector Creation System. Its titer was 8 x 10(10) pfu/ml. Ad-TbetaR-II extracellular domain-RANTES fusion gene was transfected into LA795 cells and had specific protein fragment proved by Western Blot. The concentration of TGF-beta1 was decreased and RANTES was increased in supernatant of transfected cells. The growth curve showed that recombinant adenovirus vector expressing the fusion gene could delay tumor development and induce apoptosis, with an apoptosis rate in vitro of 16.9%. The supernant of infected cells showed chemotactic activity to splenic lymphocytes. Tumor growth and survival time were prolonged significantly in group tranfected with recombinant adenovirus vector expressing the fusion gene, and tumor growth was effectively inhibited after injecting recombinant adenovirus vector expressing the fusion gene, with a tumor growth inhibition rate of 37.6%.

CONCLUSIONA recombinant adenovirus vector expressing TbetaR-II extracellular domain-RANTES fusion gene has been constructed successfully. The recombinant adenovirus vector can bind TGF-beta1 effectively, counteract immune suppression mediated by TGF-beta, enhance immune function, induce significant antitumor immune respone, inhibit tumor growth, and prolong the survival time of tumor-bearing mice.

Adenocarcinoma ; metabolism ; pathology ; therapy ; Adenoviridae ; genetics ; Animals ; Apoptosis ; Cell Line ; Cell Line, Tumor ; Chemokine CCL5 ; genetics ; metabolism ; Female ; Genetic Therapy ; methods ; Genetic Vectors ; Humans ; Lung Neoplasms ; metabolism ; pathology ; therapy ; Mice ; Neoplasm Transplantation ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Random Allocation ; Receptors, Transforming Growth Factor beta ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Transfection ; Transforming Growth Factor beta1 ; metabolism

BACKGROUNDGlucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model.

METHODSFirstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance (ANOVA) was employed for comparing means of multiple groups, followed Fisher's least significant difference (LSD) for paired comparison.

RESULTSThe rats were successfully kindled after an average of (13.50 ± 3.99) times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups (P < 0.001). The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs (P < 0.001 compared with the epilepsy group), accompanied by attenuation of seizures and improvement of electroencephalograms.

CONCLUSIONSDown-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.

Amygdala ; metabolism ; Animals ; Epilepsy ; genetics ; Kindling, Neurologic ; genetics ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUNDVibrio vulnificus (Vv) is an estuarine bacterium that can cause primary septicemia as well as serious wound infections. However, little is known about the mechanisms by which Vv infects dendritic cells (DCs) and its effects on cytoskeleton. In this study, we aimed to investigate the invasion, internalization, and the organelles damage of the cultured dendritic cells (a DC 2.4 strain) during Vv infection.

METHODSThe study model was the cultured DCs infected by a Vv 1.758 strain. Electron microscopy was used to observe the localization of bacteria at the different time points of infection, cell morphology, and the process of organelles changes. The cytoskeleton structure including the microfilaments and the microtubules rearrangement was examined under a fluorescence microscope.

RESULTSThe Vv were pinocytosised into the DC cells through double-sides, and localized at 1 - 2 mm of the inner side membrane. It took 1.3, 1.9, and 3.4 hours to reach the infection ratio of 25%, 50%, and 75%, respectively. Using electron microscopy, the DCs had been observed to have developed chromatin aggregation within 4.0 hours, and significant cytoskeleton structure disruption was noted within 6.0 hours.

CONCLUSIONThe high lethality of Vv infection may be associated with the direct disruption of the DCs cytoskeleton structure.

Animals ; Apoptosis ; physiology ; Cells, Cultured ; Cytoskeleton ; metabolism ; ultrastructure ; DNA Fragmentation ; Dendritic Cells ; metabolism ; microbiology ; ultrastructure ; Mice ; Microscopy, Electron ; Microscopy, Electron, Transmission ; Vibrio Infections ; metabolism ; Vibrio vulnificus ; pathogenicity

BACKGROUNDCentral nervous system leukemia (CNSL) is an important relapse in children with acute lymphoblastic leukemia (ALL). We investigated the possible role of endogenous hydrogen sulfide (H(2)S) of cerebrospinal fluid (CSF) in predicting CNSL.

METHODSFrom August 2008 to December 2010, 380 children were enrolled in this study at Shijitan Hospital, China. These children were from 2 to 16 years old, and the median age was 6.5 years. They were divided into a CNSL group (7 cases), a leukemia group (307 cases), a non-leukemia group (26 cases) and a healthy group (40 children). CSF specimens were obtained from conventional lumbar punctured, then centrifuged and supernatants preserved for H(2)S detection. Leukemic cells precipitates from CSF were found in three cases, the hCSE and hCBS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR), and H(2)S levels in serum were also measured. The receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the predictive diagnosis role of CSF H(2)S in children with ALL and CNSL.

RESULTSThe serum H(2)S contents of the CNSL and leukemia groups were (96.98 ± 15.77) µmol/L and (93.35 ± 17.16) µmol/L respectively, much higher than those of healthy, (44.29 ± 2.15) µmol/L, and non-leukemia, (46.32 ± 6.54) µmol/L, groups (P < 0.01). Compared with the leukemia group, CSF H(2)S content of the CNSL group was significantly high (P < 0.01). Meanwhile, in contrast to the non-leukemia group, CSF H(2)S contents of the CNSL and leukemia groups were both significantly increased (P < 0.01). In addition, leukemic cells from CSF precipitations could express CBS and CSE mRNA. Furthermore, the ROC analysis showed the UAC was 0.929 (95%CI: 0.857 - 1.000), and the optimum cut-off value of CSF H(2)S was 12.08 µ mol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively.

CONCLUSIONSCSF H(2)S contents were significantly increased in children with CNSL. After treatment, H(2)S contents were decreased subsequently. Therefore, we speculated that H(2)S levels of CSF would predict CNSL in ALL children.

Adolescent ; Central Nervous System Neoplasms ; cerebrospinal fluid ; metabolism ; pathology ; Child ; Child, Preschool ; Cystathionine beta-Synthase ; genetics ; Female ; Humans ; Hydrogen Sulfide ; cerebrospinal fluid ; Leukemia ; cerebrospinal fluid ; Lyases ; genetics ; Male

Objective To identify the presence of candidate pathogenicity island 89K DNA sequence of Streptococcus suis serotype 2 (SS2) strains isolated from patient in Zhejiang province. Methods Genes and DNA fragments were amplified by PCR, using specific primers, and three amplified fragments of the89K sequence were directly sequenced. The results were analyzed using software related to bioinformaties and epidemiology. Results 8 strains of SS2 all contained 89K sequence, cps2J and mrp virulent genes, and species-specific 16S rDNA. 3 amplified fragments of 89K candidate pathogenicity island of SS2 ZJ0501 were above 99% similar to SS2 strain identified from outbreaks in Jiangsu in 1998, and the gene fragment of coding DNA recombinant protein in the 89K sequence was highly homological with that of S. dysgalactiae and S. agalactiae. Conclusion In recent years SS2 strains isolaed from patients with clinical symptoms in Zhejiang province had been detected to have contained candidate pathogenicy 89K DNA fragment.

Chronic post-hypoxic myoclonus, also known as Lance-Adams syndrome (LAS), is a rare complication of successful cardiopulmanry resuscitation often accompanied by action myoclonus and cerebellar ataxia. It is seen in patients who have undergone a cardiorespiratory arrest, regained consciousness afterwards, and then developed myoclonus days or weeks after the event. Worldwide, 122 cases have been reported in the literature so far, including 1 case of Chinese. Here we report 2 Chinese LAS patients with detailed neuroimagings. Cranial single photon emission computed tomography (SPECT) of patient 1, a 52-year-old woman, showed a mild hypoperfusion in her left temporal lobe, whereas patient 2, a 54-year-old woman, manifested a mild bilateral decrease of glucose metabolism in the frontal lobes and a mild to moderate decrease of the N-acetyl aspartate (NAA) peak in the bilateral hippocampi by cranial [(18)F]-fluorodeoxyglucose positron emission tomographic (PET) scan and cranial magnetic resonance spectroscopy (MRS), respectively. We also review the literature on the neuroimaging, pathogenesis, and treatment of LAS.
Cardiopulmonary Resuscitation ; adverse effects ; Cerebellar Ataxia ; diagnosis ; etiology ; Female ; Humans ; Hypoxia-Ischemia, Brain ; diagnosis ; etiology ; Middle Aged ; Myoclonus ; diagnosis ; etiology ; Syndrome

Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.