BACKGROUNDIt has been reported that there is a significant difference in the local tissue concentration of transforming growth factor (TGF)-β1 between chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis without nasal polyps (CRSwNP) patients. TGF-β has been reported to play an important role in regulating epithelial cell repair in lower airway remodeling and may be a critical factor involved in the remodeling process of chronic rhinosinusitis (CRS).

METHODSEthmoidal mucosal samples collected from CRS and healthy control patients were analyzed for TGF-β1, TGF-β receptor I, TGF-β receptor II, Smad3, phospho-Smad3, Smad7, and Smad anchor for receptor activation by Western blotting analysis. The proliferation of sinonasal epithelial cells at baseline and after TGF-β1 and/or EGF stimulation was evaluated by the MTT assay.

RESULTSIn CRSsNP, TGF-β1, TGF-β receptor I, TGF-β receptor II, and Smad3 protein levels were significantly higher than controls. In CRSwNP, TGF-β1, Smad3, and pSmad3 protein levels were significantly lower than controls. Smad7 protein was significantly higher in CRS than controls. In vitro experiments demonstrated that the baseline proliferation levels of sinonasal epithelial cells were lower in CRS than controls.

CONCLUSIONSCRSwNP is characterized by a lower level of TGF-signaling compared with the control. In CRSsNP, although the upstream signaling of TGF-β was enhanced, the high Smad7 protein expression may restrain the downstream signaling components (e.g., pSmad3) and the TGF-β antiproliferative effect on sinonasal epithelium. The difference in the local tissue concentration of TGF-β1 between CRSsNP and CRSwNP patients did not result in significant differences in epithelial proliferation.

Adult ; Aged ; Benzamides ; pharmacology ; Cells, Cultured ; Dioxoles ; pharmacology ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Male ; Middle Aged ; Protein-Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism ; Receptors, Transforming Growth Factor beta ; antagonists & inhibitors ; metabolism ; Serine Endopeptidases ; metabolism ; Signal Transduction ; drug effects ; Sinusitis ; metabolism ; Smad3 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta ; metabolism ; Transforming Growth Factor beta1 ; antagonists & inhibitors ; metabolism ; Young Adult

OBJECTIVETo evaluate the effect of intranasal liposome-mediated IL-12 gene therapy on the eosinophils and IL-5 in the murine model of allergic rhinitis.

METHODSThirty-six BALB/C mice were randomly divided into allergic rhinitis (AR) group, gene therapy group and control group. Allergic rhinitis group were sensitized and stimulated by ovalbumin (OVA), and gene therapy group were administered with liposome-mediated pGEG. mIL-12 transnasally before stimulated. The eosinophils in bone marrow were counted by Wright's staining, and the eosinophils in nasal mucosa were counted by HE staining. The eosinophils of peripheral blood were detected by flow cytometry. The expression of IL-5 in bone marrow and nasal mucosa was examined by immunohistochemistry. The IL-5 in serum was detected by ELISA.

RESULTSAmong the three groups, the difference of all data was statistically significant (P<0.01). Multiple Comparison showed that the ratio of eosinophils to white cells and the mount of IL-5 positive cells in nasal mucosa and bone marrow of gene therapy group was significantly lower than that of AR group (P<0.05). The ratio of eosinophils to granulocyte (0.124 +/- 0.031) and the expression level of IL-5 [(29.51 +/- 6.68) pg/ml] in peripheral blood [ 0.184 +/- 0.079 and (56.58 +/- 16.80) pg/ml] were significantly lower in gene therapy group than in AR group (P<0.05).

CONCLUSIONSTransnasal administration of liposome- mediated pGEG. mIL-12 could depress the expression of IL-5 in bone marrow, peripheral blood, and nasal mucosa, to influence the proliferation and differentiation of eosinophils and decrease the delivery and transference of eosinophils to peripheral blood and nasal mucosa. It may be a new treatment for respiratory tract allergic inflammation.

Animals ; Eosinophils ; metabolism ; Genetic Therapy ; Interleukin-12 ; genetics ; pharmacology ; Interleukin-5 ; metabolism ; Liposomes ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa ; metabolism ; Rhinitis, Allergic, Perennial ; metabolism ; therapy

OBJECTIVETo evaluate the histopathologic changes of the ethmoid bone in CT scan typing of chronic rhinosinusitis (CRS), and investigate relations with outcomes of endoscopic surgery.

METHODSOne hundred and twelve random CRS patients undergoing endoscopic sinus surgery at Tongren hospital were prospectively evaluated. According to the preoperative CT scan, these patients were divided into three groups of CT scan typing. The bony changes and bone remodeling of ethmoid bone were graded and relations with outcomes of endoscopic surgery were investigated.

RESULTSThe CT scan typing results of ethmoid sinus of CRS were as followed: 22.3% (type III), 39.3% (type II), and 38.4% (type I). Comparison of bone remodeling and postoperative endoscopic scores between the three groups revealed a significant difference (P = 0.01, P = 0.02). A trend toward more advanced bone remodeling grade in association with a higher postoperative endoscopic scores was identified, with a statistically significant correlation.

CONCLUSIONThe Chinese CT scan typing of CRS has its pathological basis and can a useful method to predict the surgical outcomes of CRS. The new bone formation or bony tissue remodeling of sinus often represents pathogenesis of CRS and implicates the prognosis of sinus surgery.

Adult ; Chronic Disease ; Ethmoid Sinus ; diagnostic imaging ; pathology ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Sinusitis ; classification ; diagnostic imaging ; pathology ; Tomography, X-Ray Computed ; Young Adult

BACKGROUNDThe role of nasal obstruction in the pathogenesis of obstructive sleep apnea/hypopnea syndrome (OSAHS) has been debated for decades. In this prospective study, we compared the pharyngeal aerodynamic characteristics of OSAHS patients and normal people, and investigated the contribution of total nasal airway resistance to the pathophysiology of OSAHS.

METHODSComputational fluid dynamics (CFD) was used to extract the average pressure and average airflow velocity in three transverse cross-sectional planes of the pharynx for statistical analysis, and the correlation between nasal resistance and the average pressure in the pharyngeal cavity was investigated.

RESULTSThe negative pressure within the pharyngeal cavity was significantly higher in OSAHS patients than in normal subjects, and total nasal airway resistance correlated well with the average pressure in three consecutive transverse cross-sections of the pharyngeal cavity.

CONCLUSIONSGreater negative pressure within the pharyngeal cavity contributed to the increased collapsibility of the pharynx in OSAHS patients, and the strong correlation between nasal resistance and pharyngeal pressure suggests that the nose plays a role in the pathogenesis of OSAHS.

Adult ; Humans ; Middle Aged ; Pharynx ; physiopathology ; Prospective Studies ; Sleep Apnea, Obstructive ; etiology ; physiopathology

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient′s body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator′s position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient′s legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m²) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m²) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m^-2·d^-1 for 14 consecutive days followed by 7-days rest. To observe the patients′ intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.

OBJECTIVETo explore novel pathogenic mutation in the mitochondrial DNA gene in diabetic pedigree.

METHODSTwenty-eight suspected mitochondrial DNA diabetic families were recruited. The gene fragment was produced by PCR, and mutation was detected by direct sequencing.

RESULTSIn one pedigree, the proband and her mother were found carrying the most common nt3243 A --> G mutation and another 16S rRNA 3205C --> T mutation. But only 3205C --> T was found in her affected brother. All the two patients were deaf and developed diabetes in early age, characterized by impaired beta cell function and low body mass index (BMI). The proband had relatively higher lactic acid concentration than normal individuals. A novel ND1 gene 3434 A --> G(TAT --> TGT) mutation was explored in another proband with deafness and her affected family members.

CONCLUSION16SrRNA 3205C --> T mutation was found in a mitochondrial diabetes mellitus pedigree, implying its potential pathogenic role in diabetes. Another novel ND1 3434 A --> G mutation was found in another diabetic pedigree. Because this mutation causes amino acid change (Tyr --> Cys) and is co-segregated with diabetes, it may be diabetogenic.

Adult ; Asian Continental Ancestry Group ; genetics ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Diabetes Mellitus ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; RNA, Ribosomal, 16S ; analysis ; genetics

OBJECTIVESTo investigate the aerodynamics characteristics of nasal cavity in inspiration phase from 60 healthy Chinese people and provide the reference values for future computational fluid dynamics (CFD) research.

METHODSCFD was used for numerical simulation. The indices of main airflow passage, total nasal airway resistance, maximal velocity, maximal wall shear stress, nasal mucosa area, nasal volume and surface area-to-volume ratio were extracted from CFD analysis results. SPSS 16.0 software was used to analyze the data.

RESULTSThe main airflow passage in nasal cavity was common meatus, the mean total nasal airway resistance was (0.211 ± 0.085) kPa·s·L(-1), the mean maximal velocity was (12.01 ± 2.79) m/s, the mean maximal wall shear stress was (2.50 ± 0.89) Pa, the mean nasal mucosa area was (161.2 ± 34.7) mm(2), the mean nasal volume was (31.7 ± 8.1) ml and the mean surface area-to-volume ratio was (0.58 ± 0.09) mm(-1). No significant difference was detected in aerodynamics indices between male and female people.

CONCLUSIONSThe main airflow passage is located in common meatus. The nasal valve area is the key constrictive plane in nasal cavity. There are no gender differences of main airflow characteristics in nasal cavity. The normal ranges of aerodynamics indices could be used for reference values for future CFD research.

Adolescent ; Adult ; Asian Continental Ancestry Group ; Computer Simulation ; Female ; Humans ; Male ; Middle Aged ; Nasal Cavity ; physiology ; Pulmonary Ventilation ; Young Adult

Chronic Disease ; Computational Biology ; Humans ; Nasal Polyps ; Rhinitis ; Sinusitis

Objective The alterations of gut microbiota is closely related to metabolic diseases. The aim of this study was to analyze the effects of antibiotics on glucose metabolism and gut microbiota in mice, and to further explore the mechanism of gut microbiota in reducing blood glucose in db/db diabetic mice by broad-spectrum antibiotics. Methods 16 C57BL/KsJ-db/db mice were randomly divided into antibiotic group and control group with 8 mice in each group. Antibiotic group: broad-spectrum antibiotics(vancomycin 10mg/(kg·d), carbenicillin 50mg/(kg·d), metronidazole 50mg/(kg·d), neomycin 30mg/(kg·d)); Control group: 1% cellulose sodium solution as placebo treatment. Fasting blood glucose and body weights were recorded once a week during the study. At the same time, feces were collected for 16S rDNA gene sequencing analysis. The changes of fasting blood glucose, body weight, the relative abundance of microbiota, Shannon index, Simpson index and GLP-1 were compared between the two groups. Results After 5 weeks of treatment with broad-spectrum antibiotics (Vancomycin , Carbenicillin , Metronidazole , and Neomycin ), fasting blood glucose levels in db/db diabetic mice were significantly decreased (9.59±4.49mmol/L vs 19.71±8.74mmol/L,P=0.016). At the same time, antibiotics can also affect the gut microbiota of mice. The relative abundance of Proteobacteria in mice treated with antibiotics was significantly higher than that in control group (0.471±0.12 vs 0.177±0.12, P<0.05), and the OTUs of Proteobacteria, Enterobacteriaceae, Gamma-proteobacteria, and Enterobacteriales increased in mice treated with antibiotics compared with controls. In addition, we also showed antibiotics could change the diversity of gut microbiota, and the diversity of gut microbiota in antibiotic treated mice decreased significantly (Shannon index 3.135 vs 5.359, P<0.01); Simpson index 0.794 vs 0.946, P<0.01). Conclusion Broad-spectrum antibiotics can significantly reduce the fasting blood glucose level and the diversity of gut microbiota of db / db diabetic mice, and the alterations of gut microbiota may play an essential role in the process of reducing blood glucose by broad-spectrum antibiotics.

Objective In order to meet the needs of maxillofacical bone defect repair, the aim of this study was to synthesize graphene oxide(GO) modified three-dimensional conneted nano- zirconia(ZrO₂) bone tissue engineering scaffold and evaluate its surface morphology, compressive strength and cytocompatibility. Methods GO was synthesized by a modified Hummers method and then was testified by scanning electron microscope, transmission electron microscopy and fourier transform infrared spectroscopy. ZrO₂ scaffold was modified by different concentrations(0.5,1.0,1.5mg/mL) of GO dispersion via a silane-mediated method. The composite scaffold with uniform GO coating was chosen for compressive strength test and co-cultured with human dental pulp stem cells(hDPSCs). Actin staining was used to observe the growth of the cells on the scaffold, and MTS was used to detect the cell activity. Results The characterization results showed that, under scanning electron microscope, the GO was flaky and the surface morphology of folds could be seen. Part of the GO layer folds up at the edge. Under transmission electron microscopy, the GO was clearly observed to have a gossylike, translucent and slightly wrinkled lamellar structure. The crystal structure in this area in the high-resolution filter image showed a six-member ring structure like graphite. Under high power electron microscope, the 1.0mg/ml GO-ZrO₂ scaffold could be seen to deposit a thin layer of GO at the crack of the scaffold skeleton, connecting the two ends of the crack, and lamellar GO with folds could be observed on the surface of ceramic particles. The comparison of mechanical properties showed that the compression strength of GO-ZrO₂ scaffold was sgnificantly increased compared with that of ZrO₂ scaffold[（1.292±0.087）vs（1.031±0.076）, P<0.05]. Compared with the simple ZrO₂ scaffold, the GO-ZrO₂ scaffold showed more dense extension and adhesion to the surface of scaffolds, showing more active cell proliferation. The cell viability test showed that the viability of hDPSCs was significantly improved on GO-ZrO₂ scaffold after 1, 3 and 5 days of proliferation compared with the simple ZrO₂ scaffold(P<0.05). Conclusion The ZrO₂ scaffold modified by GO improved compressive strength, promoted the early proliferation of hDPSCs with good cytocompatibility.