There is no fusion fascia in the abdomen and extraperitoneal fascia always surrounds the mesentery.

Toldt's fascia has always been described as a fusion fascia formed by two layers of visceral peritoneum when the mesentery attaches to the posterior abdominal wall. However, there is still no consensus about the mesentery and its surrounding fascia based on the current anatomic theories. This study aimed to determine the anatomical structures of the abdomen and provide a correct surgical plane for mesenteric-based surgery. Surgical videos of 121 patients who underwent laparoscopic operations of the digestive tract were reviewed to identify and compare the anatomical structures of the mesentery and associated fascia. Twenty-one postoperative specimens were stained with hematoxylin and eosin to indicate the histological appearance of the mesentery and its surrounding fascia. Furthermore, dynamic models had been established to explain the formation mechanism of the associated histological structures in different regions during the progression of mesenteric attachment. The fasciae surrounding the mesentery, including the submesothelial connective tissue, the subserosal connective tissue, Toldt's fascia, and "angel hair," have the same histological characteristic to extraperitoneal fascia. The general anatomical structure of the abdomen can be divided into three layers (abdominal wall, urogenital system, and digestive system) and two interlayers (transversalis fascia and extraperitoneal fascia). The extraperitoneal fascia surrounds the entire digestive system and is the natural layer separating adjacent structures from each other. Typical histological structures in the regions of posterior attachment include the fascia propria of the mesentery, mesofascial plane, extraperitoneal fascia, retrofascial plane, and anterior renal fascia. The urogenital system is surrounded by similar histological structures. There is no fusion fascia in the abdomen due to retreat of the visceral peritoneum, and all of the fasciae surrounding the mesentery are extraperitoneal fascia. This study demonstrates that the typical histological structures in the regions of attachment and mesofascial plane are the correct anatomic interface for mesenteric-based surgery.

Evaluation of modified coblation endoscopic lingual lightening in multilevel surgery for obstructive sleep apnea hypopnea syndrome: an open intervention study.

PURPOSE: To evaluate the efficacy and safety of modified coblation endoscopic lingual lightening to address retrolingual obstruction in multilevel surgery for obstructive sleep apneae (OSA). METHODS: Patients with OSA due to retropalatal and retrolingual obstructions were enrolled. Group 1 consisted of patients who underwent modified coblation endoscopic lingual lightening combined with H-uvulopalatopharyngoplasty, while group 2 comprised patients treated by H-uvulopalatopharyngoplasty alone. Objective parameters and subjective evaluations were recorded preoperatively and at 6 months postoperatively. RESULTS: The mean (standard deviation) apnea-hypopnea index (AHI) declined from 51.5 (18.9) to 14.3 (7.2) in group 1, and from 51.7 (15.8) to 28.5 (16.9) in group 2. The mean (standard deviation) percentage change in AHI was higher in group 1 than in group 2 (73.2 [10.9] vs. 48.9 [22.4], P < 0.01). The surgical response rate differed significantly between groups 1 and 2 (88.5 [23/26] vs. 46.7 [14/30], P < 0.01). Other outcomes, including the lowest oxygen saturation, Epworth Sleepiness Scale score, snoring visual analog scale score, and subjective improvement rate, were also significantly better in group 1 than in group 2. CONCLUSION: Without increasing complications, modified coblation endoscopic lingual lightening significantly improved surgical outcomes as part of multilevel surgery in patients with OSA due to multilevel obstruction.

A combination of Beers and STOPP criteria better detects potentially inappropriate medications use among older hospitalized patients with chronic diseases and polypharmacy: a multicenter cross-sectional study.

BACKGROUND: Research on potentially inappropriate medications (PIM) and medication-related problems (MRP) among the Chinese population with chronic diseases and polypharmacy is insufficient. OBJECTIVES: This study aimed to investigate the prevalence of PIM and MRP among older Chinese hospitalized patients with chronic diseases and polypharmacy and analyze the associated factors. METHODS: A retrospective cross-sectional study was conducted in five tertiary hospitals in Beijing. Patients aged ≥ 65 years with at least one chronic disease and taking at least five or more medications were included. Data were extracted from the hospitals' electronic medical record systems. PIM was evaluated according to the 2015 Beers criteria and the 2014 Screening Tool of Older Persons' Prescriptions (STOPP) criteria. MRPs were assessed and classified according to the Helper-Strand classification system. The prevalence of PIM and MRP and related factors were analyzed. RESULTS: A total of 852 cases were included. The prevalence of PIM was 85.3% and 59.7% based on the Beers criteria and the STOPP criteria. A total of 456 MRPs occurred in 247 patients. The most prevalent MRP categories were dosages that were too low and unnecessary medication therapies. Hyperpolypharmacy (taking ≥ 10 drugs) (odds ratio OR 3.736, 95% confidence interval CI 1.541-9.058, P = 0.004) and suffering from coronary heart disease (OR 2.620, 95%CI 1.090-6.297, P = 0.031) were the influencing factors of inappropriate prescribing (the presence of either PIM or MRP in a patient). CONCLUSION: PIM and MRP were prevalent in older patients with chronic disease and polypharmacy in Chinese hospitals. More interventions are urgently needed to reduce PIM use and improve the quality of drug therapies.

CircRNA circSEPT9 Downregulates miR-10a through Methylation to Promote Cell Proliferation in Laryngeal Squamous Cell Carcinoma.

The oncogenic functions of circRNA circSEPT9 have been characterized in triple-negative breast cancer. We analyzed its role in laryngeal squamous cell carcinoma (LSCC). Quantitative reverse-transcription PCR (RT-qPCR) was used to analyze the expression of circSEPT9 and miR-10a in paired LSCC and nontumor tissues donated by 50 patients with LSCC. Methylation-specific PCR (MSP) was performed to analyze the role of circSEPT9 in miR-10a RNA gene methylation. circSEPT9 or miR-10a were overexpressed in LSCC cells to explore the interaction between them. The regulatory role of circSEPT9 and miR-10a in cell proliferation was studied with cell counting kit-8 (CCK-8) assay. CircSEPT9 was highly expressed in LSCC, whereas miR-10a was expressed at a lower level in LSCC. CircSEPT9 and miR-10a were closely correlated across LSCC tissue samples. In LSCC cells, circSEPT9 overexpression increased the methylation of the miR-10a gene and decreased the expression of miR-10a. CircSEPT9 overexpression increased LSCC cell proliferation, whereas miR-10a overexpression decreased cell proliferation. Co-transfection experiments showed that circSEPT9 overexpression attenuated the effects of miR-10a overexpression on cell proliferation. We conclude that circSEPT9 may increase miR-10a methylation to increase cell proliferation in LSCC.

Immediate Ansa Cervicalis-to-Recurrent Laryngeal Nerve Anastomosis for the Management of Recurrent Laryngeal Nerve Infiltration by a Differentiated Thyroid Carcinoma.

OBJECTIVES: The optimal surgical approach to treat recurrent laryngeal nerve (RLN) infiltration by differentiated thyroid cancer (DTC) remains a subject of debate. This study explored the feasibility and efficiency of immediate ansa cervicalis nerve (ACN)-to-RLN anastomosis for the management of RLN infiltration by DTC. MATERIAL AND METHODS: Fifty-three patients who underwent immediate ACN-to-RLN anastomosis during DTC extirpation were enrolled in the present study. Thirty-seven cases presented with unilateral vocal cord paralysis before the operation (Group A), and another 16 patients presented with normal vocal cord mobility preoperatively (Group B). Multidimensional assessments, videostroboscopy, voice assessment, and laryngeal electromyography (LEMG) were performed preoperatively and postoperatively. RESULTS: All videostroboscopy, voice assessment and LEMG parameters in Group A deteriorated 1 month after the operation and improved 1 year after the operation compared with preoperative data. In Group B, all parameters 1 year after the operation improved significantly compared with the corresponding parameters 1 month after the operation. LEMG in Group A and B provided substantial evidence for the maturation of neural regeneration from ACN and demonstrated that the laryngeal muscles were reinnervated successfully by this procedure. CONCLUSIONS: If the RLN is infiltrated by DTC, immediate ACN-to-RLN anastomosis during complete excision of DTC could restore satisfactory phonatory function and does not compromise oncological radicality.

Organ preservation surgery for patients with T4a laryngeal cancer.

PURPOSE: Surgical preservation of laryngeal function is very challenging in patients with advanced SCCL, especially those of stage T4a. The purpose of this study was to assess the feasibility of organ preservation surgery for patients with T4a squamous cell carcinoma of the larynx (SCCL). METHODS: We enrolled 32 patients with T4a SCCL and performed organ preservation surgery on them. Surgical details and perioperative morbidity were described, functional and oncologic outcomes were also evaluated. RESULTS: All patients underwent supracricoid subtotal laryngectomy with unilateral or bilateral neck dissection, restoring laryngeal function via direct anastomosis of the cricoid cartilage and tongue base. The patients recovered well and exhibited relatively acceptable survival duration, with a 5-year overall survival rate of 62.5%. Most patients commenced oral intake within 2 weeks, and aspiration was commonly observed. Subjective functional outcomes indicated a relatively acceptable swallowing function and voice quality. CONCLUSION: Our retrospective analysis of 32 patients with T4a SCCL showed that successful organ preservation surgery is safe and reliable, and associated with a relatively acceptable disease-free survival, normal swallowing function, and acceptable voice quality. More patients with T4a SCCL who wish to preserve the larynx should be considered for organ preservation surgery.

Expression of TGF-ß1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice.

Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term denervation can induce laryngeal muscle fibrosis, which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-ß1 expression peaked at 1 week after denervation (p < 0.05) and was maintained at its high level until 4 weeks. CTGF- and α-SMA-positive muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p < 0.05), and remained at high levels with a subsequent slight decrease for 3-4 weeks. These results suggest that TGF-ß1 and CTGF may be involved in the process of denervated skeletal muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies.

Risk of Gastric and Colorectal Cancer After Tamoxifen Use for Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: It is still controversial whether tamoxifen use for breast cancer will simultaneously cause gastric and colorectal cancer. In this study, we aimed to evaluate the association between tamoxifen use and the risk of gastric and colorectal cancer by performing a systematic review and meta-analysis. MATERIALS AND METHODS: A comprehensive literature search for relevant studies published from 1969 to October 2013 was performed in PubMed, MEDLINE, and ISI Web of Science. Only articles in which gastric and colorectal cancer was reported after tamoxifen therapy for breast cancer were included. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using both the random-effects and fixed-effects models. RESULTS: We found a total of 9 studies that met the inclusion criteria for the analysis of tamoxifen use and incidence of gastric and colorectal cancer. Among these studies, 7 were involved with both gastric and colorectal cancer, 1 with gastric cancer and 1 with colorectal cancer. The random-effects model results showed that tamoxifen use for breast cancer was not a risk factor for either gastric cancer (RR=0.92; 95% CI, 0.41-2.07, P=0.84) or colorectal cancer (RR=1.05; 95% CI, 0.90-1.21, P=0.54). Sensitivity analysis indicated that the duration or dose of tamoxifen use had no effect on these 2 gastrointestinal tumors (P>0.05). Stratified analysis showed that tamoxifen use was not associated with the increased risk of gastric and colorectal cancer regardless of whether the latency interval after breast cancer diagnosis was <5 or ≥5 years. CONCLUSION: Our meta-analysis results indicate that there was no substantial increase in gastric and colorectal cancer among the tamoxifen-treated female patients.

Combined use of gastric pull-up and pectoralis major flaps for massive defects after total laryngopharyngoesophagectomy in patients with advanced hypopharyngeal carcinoma.

Reconstruction for patients with advanced squamous cell carcinoma of the hypopharynx (SCCHP) after radical surgery is a challenge for head and neck surgeons, especially when one flap alone cannot entirely cover the defects. In this report, we describe the successful use of gastric pull-up combined with pectoralis major flaps for single-stage reconstruction after total laryngopharyngoesophagectomy in patients with SCCHP. We retrospectively reviewed the records of 23 patients with stage IV SCCHP who underwent this reconstructive procedure. Surgical details and perioperative morbidity were described, and functional and oncologic outcomes were evaluated. We used the gastric pull-up and pectoralis major flap procedure to reconstruct the defects for all 23 patients. In 13 patients the combined flaps were used to restore intestinal continuity, and in 10 patients the defects were repaired using gastric pull-up alone and covered by the pectoralis major flap. All the combined flaps worked well, and patients recovered normal swallowing function a mean 19.6 days after surgery. After an overall mean follow-up time of 25.3 months, six patients were still alive at the time of this analysis with no evidence of disease. Our results indicate that for patients with advanced SCCHP after total laryngopharyngoesophagectomy, using a pectoralis major flap combined with gastric pull-up enables one-stage reconstruction even when gastric pull-up alone cannot restore intestinal continuity. Furthermore, the functional and oncologic outcomes from this study suggest that this reconstructive procedure is safe and reliable, and more patients with advanced disease could be considered.

Transition of myosin heavy chain isoforms in human laryngeal abductors following denervation.

The objective of this study was to investigate the myofiber subtype transition of human posterior cricoarytenoid (PCA) muscle after the injury to recurrent laryngeal nerve (RLN). PCA muscle specimens were obtained from 38 bilateral vocal fold paralysis patients underwent arytenoidectomy. According to the duration of RLN injury, all the cases were divided into five denervation groups: 6-12 months, 1-2, 2-3, 3-6, and >6 years. The normal PCA muscles from total laryngectomy patients were chosen as controls. Immunofluorescence was adopted to detect the expression level of myosin heavy chain (MHC)-I and MHC-II in PCA muscle. Quantitative real-time PCR was also used to assess the transcriptional level of MHC subtypes (MHC-I, MHC-IIa, MHC-IIb, MHC-IIx, embryonic-MHC, and peri-natal-MHC). Immunofluorescence showed that MHC-I-positive myofibers in denervation groups were much lower than control group, respectively, while MHC-II-positive myofibers were significantly higher than control group (P < 0.05). With the extension of denervation, the number of MHC-I-positive myofibers gradually decreased, while MHC-II gradually increased and peaked in 1- to 2-year group. Transcriptional level of MHC-I, MHC-IIa, and MHC-IIb in denervation groups significantly down-regulated compared with the control (P < 0.05), respectively. However, MHC-IIx, embryonic-MHC, and peri-natal-MHC significantly up-regulated in all denervation groups, and the highest level was in 1- to 2-year denervation group. Data from the present study demonstrated that the maximum transition of MHC subtypes in human PCA muscles occurred in 1-2 years after denervation, suggesting that laryngeal reinnervation before the occurrence of irreversible transition of MHC subtypes could maintain the structural integrity of laryngeal PCA muscles.

The relationship between structural/MHC changes in upper airway palatopharyngeal muscle morphology and obstructive sleep apnea/hypopnea syndrome.

The aim of this study is to explore the relationship between structural/MHC changes in upper airway palatopharyngeal muscle morphology and obstructive sleep apnea/hypopnea syndrome. Palatopharyngeal muscle specimens were taken from 51 patients with obstructive sleep apnea hypopnea syndrome (OSAHS) who underwent uvulopalatopharyngoplasty (UPPP) resection. Patients were divided into light, medium and severe in terms of the severity of their OSAHS. There were 17 patients in each severity group. Palatopharyngeal muscle specimens were also taken from 17 patients suffering from chronic tonsillitis for comparison as the control group. All specimens were stained using Masson and observed for structural changes, especially in muscle fiber morphology, density and arrangement, as well as intermuscular connective tissues, under light microscopy. All specimens were also analyzed for MHC-I, MHC-IIa and MHC-IIb phenotype and protein expression differences using mRNA quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. The results from each group were then statistically analyzed using semi-quantitative analysis. Light microscopy with Masson staining revealed that in the control group, the muscle fibers are closely connected and arranged neatly. In specimens from patients suffering from OSAHS, the palatopharyngeal muscle fibers are larger with obvious hypertrophy and there was an increase in elastic fibers. The mucosal lamina propria was thickened, and the density of muscle fibers was reduced. Muscle fibers are not neatly arranged and degeneration was observed. The amount of muscular pathology and fibrosis corresponds to the severity of disease in the patients. In patients with severe OSAHS, the proportion of collagen to muscle fibers was increased significantly. Immunofluorescence results reveal that there were significantly more fast muscle fibers and less slow muscle fibers in the study group than the control group. mRNA quantitative reverse transcription polymerase chain reaction (RT-PCR) revealed similar results, i.e., the proportion of MHC-II palatopharyngeal muscle fibers is higher in the study group than the control group, and increases with the severity of OSAHS. Pathological change occurs in both the collagen and muscle of OSAHS patients and corresponds to the degree of severity of OSAHS. Pathological change in palatopharyngeal muscle tissues is therefore, likely to be related to the occurrence and development of OSAHS. The increase in the proportion of the MHC-1I type fibers in OSAHS patients is likely to have an effect on the amount of airway support conferred by the muscle. This is likely the reason behind the lack of clinical improvement in some patients with severe OSAHS despite surgical treatment.

The effect of patient age on the success of laryngeal reinnervation.

The objective of the study was to investigate the influence of patient age on the efficacy of laryngeal reinnervation with ansa cervicalis in unilateral vocal fold paralysis (UVFP) patients. We retrospectively reviewed 349 consecutive UVFP cases of laryngeal reinnervation with ansa cervicalis to the recurrent laryngeal nerve anastomosis. Preoperative and postoperative videostroboscopy, perceptual evaluation, acoustic analysis, maximum phonation time (MPT) and laryngeal electromyography (EMG) data were collected. Gender, age, preoperative EMG status [preoperative voluntary motor unit recruitment (VMUR)] and denervation duration were analyzed in previous multivariable logistic regression analysis. Stratification analysis was performed on patient age in the present study. All patients were divided into four groups according to their age: Group A included patients with an age less than 30 years; Group B, 30-44 years; Group C, 45-59 years; Group D, ≥60 years. Stratification analysis on patient age showed significant differences between Group A and D, Group B and D, Group C and D (P < 0.05), but no significant difference between Group A and B, Group A and C, Group B and C (P > 0.05), respectively, with regard to parameters including glottal closure, overall grade, shimmer, noise-to-harmonics ratio; but there are no significant differences among the four groups with regard to jitter. However, for MPT and postoperative VMUR, there are significant differences among the four groups expect between Group A and B. In addition, glottal closure, perceptual and acoustic parameters, MPT values and VMUR data, were significantly improved postoperatively in each age group (P < 0.01). The data from this study indicate that patient age is an influential factor of the surgical outcome of laryngeal reinnervation for UVFP patients. Laryngeal reinnervation is less effective when patient age is more than 60 years.

Changes in sleep characteristics and airway obstruction in OSAHS patients with multi-level obstruction following simple UPPP, UPPP-GA, or UPPP-TBA: a prospective, single-center, parallel group study.

OBJECTIVE: To investigate changes in S3 sleep and the apnea hypopnea index (AHI), SpO2 desaturation and CT90, and to determine changes in the degree of airway collapse and in the cross-sectional area of the retropalatal and lingual region in obstructive sleep apnea hypopnea syndrome patients. METHOD: All subjects underwent overnight polysomnography and were evaluated using Müller's test and magnetic resonance imaging at baseline, 3, and 12 months following surgery. RESULT: The mean S3 scores in patients receiving uvulopalatopharyngoplasty combined with genioglossus advancement (UPPP-GA) or UPPP combined with tongue base advancement using the Repose™ system (UPPP-TBA) noticeably increased. Marked improvement was seen in the mean AHI, LSO2, and CT90 scores 3 and 12 months following surgery compared to baseline. Airway collapsed by 25-50% in the greatest proportion undergoing surgery at the tongue base. CONCLUSION: UPPP-GA and UPPP-TBA more effectively improve S3 sleep, and mean AHI, LSO2, and CT90 scores. In addition, they effectively alleviate airway obstruction by improving the cross-sectional area of these regions.

Outcome and safety of the Montgomery T-tube for laryngotracheal stenosis: a single-center retrospective analysis of 546 cases.

OBJECTIVE: We retrospectively analyzed the surgical outcome and safety of the Montgomery T-tube for laryngotracheal stenosis. METHODS: The patients with laryngotracheal stenosis who had undergone T-tube placement between 1996 and 2010 were reviewed. The severity of the stenosis was evaluated using the Cotton-Myer staging method. The primary endpoint was the rate of successful extubation and the secondary endpoint was safety. RESULTS: 546 patients were eligible. T-tubes were successfully extubated in 342 patients 6-24 months following intubation. The initial extubation success rate was 62.3%. Laryngotracheal restenosis following extubation occurred in 192 patients, necessitating T-tube placement for a second time. The success rate for the second attempt was 58.9%. The overall success rate was 83.3%. Hemoptysis was reported in 8 patients, postoperative infection in 6 patients, wound dehiscence in 3 patients, laryngeal obstruction in 13 patients, aspiration in 12 patients, and postoperative tracheoesophageal fistula in 2 patients. CONCLUSION: This large clinical series demonstrated the safety and effectiveness of the T-tube for grade 1 and 2 stenosis with stenosed segments of <6 cm. For those being >6 cm, tracheal end-to-end anastomosis is not appropriate and long-term placement of a T-tube is recommended. Our findings provide useful guidance for preoperatively selecting patients with laryngotracheal stenosis of various causes and differing severity.

Characterization of upper airway obstruction by fiber-optic nasolaryngoscopy and MRI in preoperative OSAHS patients.

OBJECTIVE: To investigate changes in the upper airway and its surrounding soft tissue and to characterize the extent and severity of upper airway obstruction in 136 obstructive sleep apnea/hypopnea syndrome (OSAHS) patients who were awake. METHODS: OSAHS patients and healthy controls were evaluated by fiber-optic nasolaryngoscopy and MRI. The cross-sectional area and pharyngeal wall thickness of the retropalatal, retroglossal and epiglottic region were determined. RESULTS: Ninety-five percent of the mild OSAHS subjects had single-plane obstruction (vs. severe OSAHS, p < 0.05), 5.0% of the mild OSAHS subjects had two-plane obstruction (p < 0.05) and none of them had three-plane obstruction (p < 0.05). The cross-sectional area of the retropalatal, retroglossal and epiglottic region progressively declined as the severity of OSAHS increased (severe OSAHS vs. controls, p < 0.05). The lateral pharyngeal wall was significantly thicker in OSAHS subjects than in healthy controls (p < 0.05). The cross-sectional area of the soft palate in moderate and severe OSAHS subjects was markedly larger than that of the healthy controls (p < 0.05) and positively correlated with the apnea/hypopnea index (p < 0.05). CONCLUSION: Moderate and severe OSAHS patients exhibit multi-plane obstruction of the upper airway, particularly in the retropalatal and retroglossal region. The severity of OSAHS negatively correlates with the thickness, length and cross-sectional area size of the soft palate.

Inhalation of Carboxymethyl Chitosan Alleviates Posttraumatic Tracheal Fibrosis.

OBJECTIVES: The present study was performed to determine whether the inhalation of carboxymethyl (CM)-chitosan can alleviate tracheal fibrosis in a rabbit model. METHODS: We designed a rabbit model of tracheal stenosis involving electrocoagulation with a spherical electrode. Twenty New Zealand white rabbits were randomly divided into experimental and control groups (10 animals each). Tracheal damage was successfully established by electrocoagulation in all animals. The experimental group was given CM-chitosan (inhalation for 28 days), while the control group inhaled saline. The effects of CM-chitosan inhalation on tracheal fibrosis were analyzed. Laryngoscopy was performed to evaluate and grade tracheal granulation, while tracheal fibrosis was evaluated by histological examination. The effects of CM-chitosan inhalation on the tracheal mucosa were examined by scanning electron microscopy (SEM), and hydroxyproline content in tracheal scar tissue was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Laryngoscopy showed that the tracheal cross-sectional area was smaller in the experimental than control group. The amounts of loose connective tissue and damaged cartilage, as well as the severity of collagen and fibrosis, decreased following inhalation of CM-chitosan. According to the ELISA, the experimental group had low levels of hydroxyproline in the tracheal scar tissue. CONCLUSION: The findings presented here showed that inhalation of CM-chitosan mitigated posttraumatic tracheal fibrosis in a rabbit model, thus suggesting a potential new treatment for tracheal stenosis.

SCUBE3 Exerts a Tumor-Promoting Effect in Tongue Squamous Cell Carcinoma by Promoting CEBPA Binding to the CCL2 Promoter.

Tongue squamous cell carcinoma (TSCC) is the main pathologic subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration, and invasion, induced apoptosis as well as cell cycle arrest in G2-phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, STAT3 signaling contributed to CCL2-mediated phenotypes in TSCC cells. IMPLICATIONS: Our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC.

Chronic pain exacerbates memory impairment and pathology of Aß and tau by upregulating IL-1ß and p-65 signaling in a mouse model of Alzheimer's disease.

BACKGROUND: Chronic pain is linked to cognitive impairment; however, the underlying mechanisms remain unclear. In the present study, we examined these mechanisms in a well-established mouse model of Alzheimer's disease (AD). METHODS: Neuropathic pain was modeled in 5-month-old transgenic APPswe/PS1dE9 (APP/PS1) mice by partial ligation of the sciatic nerve on the left side, and chronic inflammatory pain was modeled in another group of APP/PS1 mice by injecting them with complete Freund's adjuvant on the plantar surface of the left hind paw. Six weeks after molding, the animals were tested to assess pain threshold (von Frey filament), learning, memory (novel object recognition, Morris water maze, Y-maze, and passive avoidance), and depression-like symptoms (sucrose preference, tail suspension, and forced swimming). After behavioral testing, mice were sacrificed and the levels of p65, amyloid-ß (residues 1-42) and phospho-tau in the hippocampus and cerebral cortex were assayed using western blotting, while interleukin (IL)-1ß levels were measured by enzyme-linked immunosorbent assay. RESULTS: Animals subjected to either type of chronic pain showed lower pain thresholds, more severe deficits in learning and memory, and stronger depression-like symptoms than the corresponding control animals. Either type of chronic pain was associated with upregulation of p65, amyloid-ß (1-42), and IL-1ß in the hippocampus and cerebral cortex, as well as higher levels of phosphorylated tau. CONCLUSIONS: Chronic pain may exacerbate cognitive deficits and depression-like symptoms in APP/PS1 mice by worsening pathology related to amyloid-ß and tau and by upregulating signaling involving IL-1ß and p65.

Evaluation of prescription review and feedback policy on rational antibiotic use in primary healthcare settings in Beijing, China: a qualitative study using the Theoretical Domains Framework and the behaviour change wheel.

Objectives: To decelerate antibiotic resistance driven by inappropriate antibiotic prescribing, a prescription review and feedback (PRF) policy is implemented in primary healthcare institutions (PHIs) in Beijing, China. However, evaluation of PRF implementation in PHIs is scarce. This study aims to systematically identify the barriers and facilitators of PRF policy implementation to provide evidence for antimicrobial stewardship. Methods: We conducted key informant interviews with 40 stakeholders engaged in the implementation of PRF in Beijing, including physicians, pharmacists and administrators. Interviews were audio recorded and transcribed verbatim. We coded the interview transcripts and mapped informant views to domains of the Theoretical Domains Framework. We then used a behaviour change wheel to suggest possible behavioural interventions. Results: Procedural knowledge (Knowledge) and skills (Skill) of PRF were possessed by stakeholders. They felt responsible to promote the appropriate use of antibiotics (Social/professional role and identity) and believed that PRF could help to change inappropriate provider behaviours (Behavioural regulation) in prescribing antibiotics (Beliefs about consequences) under increased intention on antibiotic use (Stages of change). Moreover, informants called for a more unified review standard to enhance PRF implementation (Goals). Frequently identified barriers to PRF included inadequate capacity (Skill), using punishment mechanism (Behaviour regulation), reaching consistently lower antibiotic prescription rates (Goals), lack of resources (Environmental context and resources) and perceived pressure coming from patients (Social influences). Conclusions: Stakeholders believed that PRF implementation promoted the rational use of antibiotics at PHIs in Beijing. Still, PRF was hampered by inconsistencies in review process and resources needed for PRF implementation.

Rapid Separation of Asiatic Acid, Quercetin, and Kaempferol from Traditional Chinese Medicine Centella asiatica (L.) Urban Using HSCCC-Semi-Prep-HPLC and the Assessment of Their Potential as Fatty Acid Synthase Inhibitors.

The main objective of this study was to rapidly separate asiatic acid (AA), quercetin (QCN), and kaempferol (KPL) from Centella asiatica (L.) Urban using high-speed counter-current chromatography (HSCCC) in tandem with the UV detector of semipreparative high-performance liquid chromatography (Semi-Prep-HPLC) and to evaluate their potential as inhibitors of fatty acid synthetase (FAS). To efficiently prepare large amounts of AA, QCN, and KPL from Centella asiatica (L.) Urban, rapid and simple methods by HSCCC were established respectively based on the partition coefficients (K values) of crude samples. The conditions of HSCCC-Semi-Prep-HPLC for the large-scale separation of AA, QCN, and KPL from Centella asiatica (L.) Urban were established and optimized. This included selecting the solvent system, flow rate, rotation speed, and so on. HSCCC-Semi-Prep-HPLC was successfully applied to separate and purify AA, QCN, and KPL, with n-hexane-n-butanol-methanol-water (3 : 1 : 3 : 3, V : V : V : V) as the solvent system for AA, which was detected at a wavelength of 210 nm with the stationary phase retention of 70%, and with n-hexane-ethyl acetate-methanol-water (0.8 : 0.9 : 1.2 : 1, V : V : V : V) as the solvent system for the co-separation of QCN and KPL, which was detected at a wavelength of 254 nm with the stationary phase retention of 65%. AA could be isolated at a large scale with high purity (>91.0%) in only one-step HSCCC-Semi-Prep-HPLC separation (within 150 min) under the optimized conditions. Meanwhile, QCN and KPL could be simultaneously isolated at a large scale with high purity (>99.1%) by another one-step HSCCC-Semi-Prep-HPLC separation (within 240 min) under the optimized conditions. The assessment of inhibition potential revealed that AA exhibited the strongest inhibitory effect on FAS, with an IC50 of 9.52 ± 0.76 µg/mL. Madecassic acid (MA) followed closely with IC50 values of 10.84 ± 0.92 µg/mL. QCN and KPL showed similar and relatively weaker inhibitory effects on FAS, with IC50 values of 43.09 ± 2.98 µg/mL and 36.90 ± 1.83 µg/mL, respectively. Overall, the HSCCC-Semi-Prep-HPLC method proved to be a highly efficient and reliable technique for separating AA, QCN, and KPL from Centella asiatica (L.) Urban, and the isolated compounds showed potential as FAS inhibitors.