Objective:To evaluate the clinical efficacy of nasal pedicle tissue flap based on nasal blood supply in the reconstruction of nasal skull base defects.Methods:A retrospective analysis was conducted on 138 clinical cases of skull base tumors and cerebrospinal fluid rhinorrhea treated at the Department of Otolaryngology, Head and Neck Surgery at Xiangya Hospital of Central South University from March 2017 to March 2023. A total of 79 males and 59 females were enrolled, aged from 8 to 82 years, with a median age of 51 years, including 108 patients (78.3%) with skull base tumors and 30 patients (21.7%) with cerebrospinal fluid rhinorrhea (and/or meningoencephalocele). During the surgery, 88 cases (63.8%) were repaired with nasal septal mucosal flaps pedicled with the posterior nasal septal artery, 14 cases (10.1%) with mucosal flaps pedicled with the anterior ethmoidal artery on the lateral wall of the nasal cavity, 6 cases (4.3%) with mucosal flaps pedicled with the posterior lateral nasal artery on the lateral wall and nasal floor, 12 cases (8.7%) with mucosal flaps pedicled with the anterior ethmoidal artery and posterior ethmoidal artery, and 18 cases (13.0%) with nasal septal mucosal extension flaps pedicled with the sphenopalatine artery or internal maxillary artery. Patients were followed up for 12 to 72 months postoperatively. Endoscopic examination or skull base enhanced MRI was performed to assess the growth and tumor recurrence in the skull base repair area. The t-test was used for statistical analysis.Results:Among 138 patients, primary repair was successful in 133 patients (96.4%), while 5 patients (3.6%) experienced postoperative cerebrospinal fluid rhinorrhea. These 5 patients all underwent nasal septal mucosal flap repair with the posterior nasal septal artery as the pedicle. Complications included 1 case of mucosal flap necrosis, 1 case of mucosal flap central perforation, and 3 cases of mucosal flap survival peripheral leakage, of which were all successfully treated with a second repair.Conclusion:The use of nasal pedicle mucosal flap based on nasal blood supply is a reliable, safe, and effective technique for repairing skull base defects.

In recent years, exosomes had been recognized as a potential cell-free therapeutic tool in the field of regenerative medicine due to their easy accessibility, low immunogenicity, and good therapeutic effect. As paracrine products of cells, exosomes not only have the functions of their donor cells but also involve fewer ethical disputes. They are more stable than traditional stem cell therapy, and easy to store, transport and sterilize, which are gradually applied in the field of oral regenerative medicine. This article provides a review of the general properties of exosomes and their application in the field of oral regeneration, with a view to exploring new pathways for functional regeneration of the stomatognathic system.

Objective To investigate the expression of Midkine(MDK)in cholangiocarcinoma(CCA)and its value in predicting the prognosis of CCA,as well as the potential mechanism of the effect of MDK on the progression of CCA.Methods The data of CCA samples were obtained from TCGA database to analyze the difference in the expression of MDK between cancer tissue and paracancerous tissue and its association with clinical features,and the data collected from GEO database and 11 CCA patients who underwent surgical resection in The Fifth Medical Center of Chinese PLA General Hospital from June 2018 to September 2021 were used for validation.STRING and Cytoscape were used to construct a protein-protein interaction network,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were used to investigate the biological functions and tumor-related pathways involving MDK-related genes.In addition,TIMER and TISIDB databases were used to analyze the correlation between MDK expression and immune cell infiltration in CCA tissue.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the Fisher's exact test was used for comparison of categorical data between two groups.The Kaplan-Meier method was used to plot survival curves,and the Log-rank test was used for comparison between groups.The Spearman correlation analysis was used to investigate the correlation between two variables.Results The expression level of MDK in cancer tissue and paracancerous tissue of CCA patients was compared based on TCGA database,and the results of the non-paired and paired analyses showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in paracancerous tissue(P<0.001).Transcriptome sequencing was performed for the tumor tissue and its corresponding paracancerous tissue from 11 CCA patients,and the results showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in corresponding paracancerous tissue(P<0.01).High expression of MDK was associated with lymph node metastasis(P=0.045)and vascular invasion(P=0.044).Survival analysis showed that compared with the CCA patients with low MDK expression,the CCA patients with high MDK expression had significantly shorter overall survival time(χ2=5.30,P=0.028)and disease-specific survival time(χ2=6.25,P=0.019).The GO and KEGG enrichment analyses showed that the 30 MDK-related genes were closely associated with ubiquitin-mediated proteolysis and affected the prognosis of CCA patients.The TIMER analysis showed that the expression level of MDK was positively correlated with the infiltration of B cells(r=0.356,P=0.035 6)and dendritic cells(r=0.409,P=0.014 7)in tumor microenvironment of CCA;the TISIDB analysis showed that the expression level of MDK was positively correlated with CXCL16(r=0.465,P=0.004 67)and was negatively correlated with CXCL12(r=-0.389,P=0.019 7)and CXCR5(r=-0.393,P=0.018 5),and it was also negatively correlated with the immune checkpoint regulators VTCN1(r=-0.393,P=0.018 3),LTA(r=-0.380,P=0.022 7),and PVR(r=-0.350,P=0.037 3).Conclusion High expression of MDK is associated with poor prognosis in CCA patients,and MDK has the potential of being used as a molecular marker for predicting the prognosis of CCA.MDK may promote the development and progression of CCA by regulating ubiquitin-mediated proteolysis and the infiltration of B cells and dendritic cells.

Objective To establish and evaluate chemotherapeutic phlebitis model rats induced by vinorelbine via the dorsalis pedis vein.Methods Rats were divided randomly into control and 4 different concentration of vinorelbine-induced model groups.Control rats were injected with 0.1 mL normal saline via the dorsalis pedis vein of the hind limb,while other rats were injected with different concentrations of vinorelbine(2,3,4,5 mg/mL),as above.General observations were performed and the hind limb volume was measured daily for 7 consecutive days to calculate the swelling rate.The rats were then killed and histological changes in the dorsalis pedis vein were observed by hematoxylin and eosin staining.Microstructural changes on the surface of the vascular endometrium were observed by scanning electron microscopy.Results Injection of 2,3,4,5 mg/mL vinorelbine via the dorsalis pedis vein significantly induced hind limb swelling in a concentration-dependent manner,peaking on day 3 in each group.The phlebitis rates on day 7 were 50%in the 2 mg/mL group and 83.3%in the 3 mg/mL group.Phlebitis was also induced in the 4 mg/mL and 5 mg/mL groups,including grade Ⅲ in 66.6%and grade Ⅳ in 83.3%.Histopathology showed inflammatory cell infiltration,wall thickening,lumen stenosis,and thrombosis in the tissues surrounding the veins.Scanning electron microscopy showed destruction of tight junctions of venous endothelial cells,and a rough surface of the vascular lining,resultsing in blood cell adhesion.Conclusions Injection of 0.1 mL of 3～5 mg/mL vinorelbine via the dorsalis pedis vein could induce red,swollen,and cord-like veins,as well as infiltration of inflammatory cells around the vein,thickened vein walls,lumen stenosis,and thrombosis.In addition,the surface of the venous intima was rough and adhered to numerous blood cells.All these features are consistent with those of clinical chemotherapeutic phlebitis in terms of the symptoms and pathological structure.

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

Objective:To investigate the trend of postoperative cavity status in patients with eosinophilic chronic sinusitis with nasal polyps (eCRSwNP) who underwent total nasalization surgery and partial reboot surgery. And to discuss the relationship between tissue eosinophil counts and status of postoperative cavity.Methods:Patients with eCRSwNP in four tertiary medical centers (Longgang ENT Hospital, Xiamen Humanity Hospital, Guangdong Clifford Hospital and the First Affiliated Hospital of Sun Yat-Sen University) from March 2018 to October 2021 were divided into 2 groups. The group without previous surgery history was performed for the nasalization surgery, and another group with previous surgery history underwent the part-reboot surgery. The follow-up time after operation was defined as the following 5 stages: 6, 12, 20-24, 36 and more than 42 months. According to FESS-95 Guangzhou standard, status of sinus cavity was assessed and classified into 3 categories: good, better and bad. The association between the sinus cavity status and tissue eosinophil counts in the above 5 stages was analyzed by one-way ANOVA, and P<0.05 was considered statistically significant. Results:A total of 72 eCRSwNP patients finished the follow-up in this study. There were 47 males and 25 females in these patients, aged from 11 to 67 years. A total of 50 cases underwent nasalization surgery and 22 cases underwent partial reboot surgery. With the follow-up time from 6 to 48 months, there were 72 cases (100.0%) who completed 6 months and 12 months follow up, 46 cases (63.9%) for 20-24 months, 36 cases (50.0%) for 32-36 months and 16 cases (22.2%) with the follow-up time more than 42 months. No matter what kind of surgery, there was no "bad" situation of the surgical cavity status 6 months after the operation, and the differentiation gradually occurred more than 12 months after the surgery. Moreover, the rates of "good" cavity status for the 5 stages in the group of nasalization surgery were 78.0%, 66.0%, 56.7%, 47.6% and 42.9%, and were 63.6%, 45.5%, 25.0%, 20.0% and 11.1% in the partial reboot surgery group, respectively, suggesting that the status of nasal cavity in nasalization surgery group was always better than that in partial reboot surgery group in every period. In addition, the "bad" rate was 0, 8.0%, 10.0%, 14.3% and 28.6% in the group of nasalization surgery, and was 0, 27.3%, 18.8%, 33.3% and 55.6% in the partial reboot surgery group, respectively. The average percentage of tissue eosinophil counts in the 72 cases was 42.1%, which had no obvious effect on the status of the surgical cavity ( P>0.05). Conclusions:For eCRSwNP patients, the operative cavity status in the patients without previous operation history treated with nasalization surgery is good. The time of 1-2 years after surgery is the main period for sinus lesions. The counts of tissue eosinophils has no significant influence on surgical sinus cavity status in the eCRSwNP patients.

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database-cFos-ANAB-a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users' purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net .
Animals ; Fear ; Mice ; Neurons ; Proto-Oncogene Proteins c-fos ; Rats

Objective:To evaluate the clinical efficacy of Buyang-Huanwu Decoction combined with modified Tingli-Dazao-Xiefei Decoction on the basis of conventional western medicine therapy in the treatment of chronic heart failure (CHF) with syndrome of qi deficiency and blood stasis. Methods:Seventy patients who met the inclusion criteria from November 2017 to November 2019 in Shijingshan District Hospital of Traditional Chinese Medicine were randomly divided into two groups, 35 in each group. The control group was treated with western medicine for chronic heart failure, and the treatment group was treated with Buyang-Huanwu Decoction combined with Tingli-Dazao-Xiefei Decoction on the basis of the control group. Both groups were treated for 2 weeks. The TCM syndrome scores were observed and compared before and after treatment. Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used to evaluate the quality of life of patients. Lee’s Heart Failure Score was used to evaluate the severity of symptoms. The N-terminal pro-B type natriuretic peptide(NT-proBNP) was detected by ELISA. The adverse reactions during treatment were observed and the clinical efficacy was evaluated. Results:The total effective rate was 91.4% (32/35) in the treatment group and 77.1 % (27/35) in the control group, and the difference was statistically significant ( χ2=7.050, P=0.014). After treatment, the serum NT-proBNP in the treatment group [(1 725.3 ± 1 473.8) ng/L vs. (2 485.7 ± 2 164.4) ng/L; U=341.200, P=0.031] was significantly lower than that of the control group. The NT-proBNP [(54.3 ± 26.7) % vs. (35.5 ± 19.8)%; U=4.310, P=0.003] was significantly higher than that of the control group. After treatment, the TCM syndrome scores and MLHFQ scores in the treatment group were significantly lower than those in the control group ( t=3.785, 9.925, P=0.031, 0.001). During the treatment, no obvious adverse reactions were observed in both groups. Conclusion:On the basis of standardized treatment of Western medicine, Buyang-Huanwu Decoction and Tingli-Dazao-Xiefei Decoction can improve the clinical efficacy of CHF patients with qi deficiency and blood stasis syndrome, promote the repair of damaged myocardium (reduce NT-proBNP), and improve the quality of life of patients.

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database—cFos-ANAB—a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users’ purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net.

Objective:The diagnostic values of urine free and fractionated catecholamine metabolites (including metanephrine MN and normetanephrine NMN, usually known as MNs) were established and their clinical value was evaluated.Methods:Using high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS), urine free MNs (f-MN, f-NMN) and fractionated MNs(t-MN, t-NMN) from 180 cases of non-pheochromocytoma and 54 cases of pheochromocytoma (PCC)patients were detected respectively.Receiver operating characteristic curve (ROC) was used to establish clinical reference cut-off value for different forms of MNs, and diagnostic efficacy of free, fractionated and total MNs was evaluated.Results:(1) The cut-off values of f-MN, f-NMN, t-MN and t-NMN were 47.8 μg/24 h, 52.3 μg/24 h, 224.9 μg/24 h and 664 μg/24 h, respectively. The cut-off values of total f-MNs and total t-MNs were 126 μg/24 h and 1 070 μg/24 h, respectively. (2) The correlation between f-MN and t-MN ( r=0.976, P<0.001), f-NMN and t-NMN ( r=0.940, P<0.001) was good. The area under ROC curve(AUC)of f-MN was lower than that of t-MN(0.579 vs 0.730, P<0.001), the sensitivity was slightly lower than that of t-MN((37.01% vs 51.85%, P=0.036), and the specificity was similar (99.44% vs 96.67%, P>0.05). There was no significant difference in sensitivity (90.74% vs 92.59%, P>0.05), specificity (99.44% vs 96.67%, P>0.05) and AUC (0.944 vs 0.959, P>0.05) between f-NMN and t-NMN. The combined diagnostic value of MN and NMN (total MNs) was higher than MN (free type:0.932>0.579, fractionation type: 0.960>0.730), which was similar to NMN. Conclusions:The diagnostic performance of urine free NMN or total MNs for PCC is similar to that of fractionated typewhich can meet the clinical needs.With few influencing factors, free type MNs may be used as an alternative indicator for PCC screening in the future.