Objective To investigate the role and mechanism of NLRP3/Caspase-1/IL-1 β inflammasome pathway in the formation of aortic dissection in mice.Methods Fifty male C57BL/6 mice(3 weeks old,body weight 10～13 g)were divided into control group(n =10,normal diet),β-aminopropionitrile(BAPN)group[n =20,drink water containing 1 g/(kg·d)BAPN],and BAPN+MCC950 group[n=20,drink water containing 1 g/(kg·d)BAPN and intraperitoneal injection of 20 mg/(kg·d)NLRP3 inhibitor,MCC950]by random sampling.Water intake,body weight,incidence of aortic dissection and aortic dissection-related mortality were recorded.The inflammatory infiltration in the aorta was observed with HE staining,elastic fiber breakage was observed by elastic Van Gieson(EVG)staining,average fluorescence intensity of NLRP3,IL-1β,α-SMA and OPN was detected by immunofluorescence assay,and protein expression levels of NLRP3,Caspase-1,ASC,IL-1β,α-SMA and OPN were measured with Western blotting.Results No aortic dissection or death was observed in the control group.The BAPN group had an incidence of aortic dissection of 80％,aortic dissection-related mortality of 35％,and obvious broken elastic fibers and inflammatory infiltrate in the aortic wall,and increased expression levels of NLRP3,Caspase-1,ASC and IL-1 β,decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group(P<0.05).While MCC950 treatment decreased the incidence of aortic dissection(80％vs 35％,P=0.004)and aortic dissection-related mortality(35％vs 15％,P=0.144),alleviated the broken elastic fibers and inflammatory infiltrate in the aortic wall,and down-regulated the expression of NLRP3,Caspase-1,ASC and IL-1β,enhanced contractile α-SMA and decreased the synthetic protein when compared with the BAPN group(P<0.05).Conclusion The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1 β inflammasome pathway.NLRP3 inhibitor,MCC950,can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.

Objective To compare the synergies between the transcutaneous needle electrodes and the ETT surface electrodes used for neurological surveillance in thyroidology,and explore how to identify and protect recurrent laryngeal nerve and vagus nerve when the patient is not suitable for oral plug or surface electrodes are failure.Methods To collect and analyze the clinical data of 32 patients undergoing surgical treatment for thyroid disease,a total of 40 neurons of the recurrent laryngeal nerves and vagus nerves were monitored,and the amplitude and latency were recorded using ETT surface electrodes and transcutaneous needle electrodes for nerve monitoring,respectively.SPSS 26.0 software was used for statistical analysis,paired t-tests were used to analyze and compare the latency periods,and the rank sum test was used to analyze whether there is a difference in the amplitude obtained from stimulation of transcutaneous needle electrodes and ETT surface electrodes.Results When the transcutaneous needle electrodes were used in thyroid surgery,we identified all the nerves,obtained two-phase electrical signals similar to the latency and amplitude of the ETT surface electrodes,and could effectively identify the recurrent laryngeal nerve and vagus nerve[(3.22±0.50)ms vs.(3.85±1.00)ms,P＜0.05]through the incapacity period,with no obvious difference in the monitoring effect from the ETT surface electrodes[(3.04±0.58)ms vs.(3.89±1.07)ms,P＜0.05].At the same time,the visualization and safety of transcutaneous needle electrodes were higher,with great advantages.Conclusion Transcutaneous needle electrodes can effectively assist in identifying and protecting the recurrent laryngeal nerve and vagus nerve,and thus are an important supplement to ETT surface electrodes.

BACKGROUND:Accurate reduction of ankle fractures under direct vision has become a common understanding among foot and ankle surgeons.How to fully expose free or compressed fragments of the posterior ankle remains one of the most challenging problems. OBJECTIVE:To explore the clinical efficiency of the para-Achilles tendon approach in exposing and repositioning the posterior malleolus sandwich fracture. METHODS:A retrospective study was made for 26 patients with posterior malleolus sandwich fracture treated with open reduction and internal fixation via para-Achilles tendon approach from January to December 2020 in The Second People's Hospital of Dalian.21 of 26 cases were managed with the lateral approach of Achilles tendon and 5 cases were managed with the medial approach of Achilles tendon.There were 19 males and 7 females,with the age of 24-69 years,averagely 38.6 years.The operation time and postoperative complications were recorded.The fracture reduction condition was evaluated by Burwell-Charnley imaging standard.Before operation,3 months after operation and last follow-up,visual analog scale score,ankle plantar flexion and dorsiflexion and American Orthopedic Foot&Ankle Society Ankle Hind Score were used to evaluate the treatment effect. RESULTS AND CONCLUSION:(1)All 26 patients were followed up for an average of 14.6 months(range 13-18 months).The operation time was 52-85 minutes(average 64.2 minutes).(2)Part of the skin edge of the lateral malleolus incision was necrotic in one patient and healed completely after a dressing change.Incision healing of the other patients was in one stage.(3)Through Burwell-Charnley imaging standard,anatomical reductions were obtained in 24 of 26,and good reductions were in 2 of 26,with an excellent and good rate of 100%.(4)At the last follow-up,the visual analog scale score(1.19±0.40)was significantly lower than the preoperative score(6.81±0.80)(P<0.01).Ankle plantar flexion(33.5±5.02)° and ankle plantar back stretch(17.23±0.99)° were significantly increased compared with preoperative data(14.58±2.50)° and(5.81±1.02)°(P<0.01).American Orthopedic Foot&Ankle Society Ankle Hind Score was improved to(89.31±3.62)points compared to preoperative(46.00±5.45)points(P<0.01).The results were excellent in 23 patients and good in 3 patients,with an excellent and good rate of 100%.(5)It is concluded that the open reduction and internal fixation via the para-Achilles tendon approach for the treatment of posterior malleolus sandwich fracture were efficient with decreased operation time,satisfying fracture reduction,fewer complications,satisfactory motion range,and functional recovery.

Objective To identify factors associated with gastrointestinal heat retention in preschool children,and to provide a foundational understanding for future clinical investigations. Methods A case-control study was performed,which involved children from kindergartens in the Longgang District of Shenzhen City,Guangdong Province,from May to July 2021. Using the Children's Gastrointestinal Heat Retention Diagnostic Self-assessment Scale,subjects were allocated into a case group (children diagnosed with gastrointestinal heat retention) and a control group (children without this condition). An online survey was used to collect data on dietary behaviors,caregivers' feeding behaviors,early antibiotic use,daily routines,and birth conditions. SPSS 27.0 software was used to facilitate precise sociodemographic matching and paired logistic regression analysis to explore the association between gastrointestinal heat retention and the above factors. Results From the analysis of 51,252 matched cases,the study found that several factors contributed to an increased risk of gastrointestinal heat retention. These factors included reduced food intake compared to peers,reports of picky eating by caregivers,distractions during meals,pronounced dietary preferences,disinterest in food,meal durations ≥ 25 min,reluctance to sample new foods,consistent refusal of specific food types for over one month,irregular meal locations,coercive feeding practices,use of micronutrient supplements,allowing children too much freedom in food choice,persuading children to eat,infrequent encouragement to experiment with new foods,early antibiotic introduction,inadequate sleep,and premature birth (P<0.05). In contrast,exclusive breastfeeding in the first six months,engagement in moderate to massive physical activity,and regular napping patterns were associated with a reduced risk of gastrointestinal heat retention (P<0.05). Conclusion The suboptimal dietary habits,improper feeding practices,insufficient physical activity,inadequate sleep,and premature antibiotic exposure may be significant risk factors for gastrointestinal heat retention. Future research dedicated to unraveling the cause of gastrointestinal heat retention should prioritize these elements.

Objective:To evaluate the clinical outcomes of Chaput tuberosity osteotomy and lateral malleolus sagittal osteotomy in the treatment of talus osteochondral lesions with autologous osteochondral transplantation (AOT).Methods:From January 2017 to December 2019, Chaput tuberosity osteotomy and lateral malleolus sagittal osteotomy were performed in the AOT treatment of 11 patients with talus osteochondral lesions. They were 9 men 2 women, with a mean age of 32. 6 years (range, from 22 to 45 years). Their lesions were all Hepple type V. Their American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS), International Knee Documentation Committee Knee Evaluation Form (IKDC) score, and imaging data were measured pre- and post-operatively for assessment of clinical outcomes.Results:All the patients were followed up for 13 to 24 months (average, 15.6 months). Their AOFAS (94.3±2.9) and VAS (1.2±0.4) scores at the final follow-up were significantly improved compared with the pre-operative values (49.5±6.6 and 5.7±1.2) ( P<0.05). There was no significant difference between their pre- and post-operative IKDC scores for the ipsilateral knee joint ( P>0.05). The imaging showed that the talus cystic change disappeared and the grafted bone was fully fused with the talus with no abnormal change in the joint space. Conclusion:In the AOT treatment of talus osteochondral lesions, Chaput tuberosity osteotomy and lateral malleolus sagittal osteotomy can obviously relieve ankle pain and improve ankle function.

OBJECTIVES: Genetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC. METHODS: A total of 31 patients with advanced NPC, who came from the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University/Hunan Provincial Cancer Hospital, were enrolled. All of the exons of 288 genes, introns of 38 genes and promoters or fusion breakpoint regions from the nasopharyngeal biopsy tissues before treatment were detected by the gene sequencing platform Illumina NextSeq CN500. The coding regions of 728 genes were carried out a high-depth sequencing of target region capture, and the 4 variant types of tumor genes (including point mutations, insertion deletions of small fragments, copy number variations, and currently known fusion genes) were detected. All of 31 patients received platinum-based induction chemotherapy combined with concurrent chemoradiotherapy and were followed up for a long time. RESULTS: The 3-year regional failure-free survival (RFFS) and disease-free survival (DFS) in patients with PI3K-Akt pathway mutation were significantly lower than those in unmutated patients (χ²=6.647, P<0.05). The 3-year RFFS and DFS in patients with mTOR pathway mutations were significantly lower than those in unmutated patients, and there was significant difference (χ²=5.570, P<0.05). The rate of complete response (CR) in patients with unmutated AMPK pathway was significantly higher than that in patients with mutation at 3 months after treatment (P<0.05), and the 3-year RFFS and DFS in patients with AMPK pathway mutation were significantly lower than those in unmutated patients (χ²=4.553, P<0.05). PI3K-Akt/mTOR/AMPK signaling pathway mutations and pre-treatment EB virus DNA copy numbers were independent prognostic factors for 3-year RFFS and DFS in patients with NPC (both P<0.05). CONCLUSIONS The NPC patients with PI3K-Akt/mTOR/AMPK signaling pathway mutation have poor prognosis, and the detection of PI3K-Akt, mTOR, AMPK driver genes and signaling pathways by next-generation sequencing is expected to provide new idea for basic research and targeted therapy of NPC.
AMP-Activated Protein Kinases/metabolism* ; DNA Copy Number Variations ; Humans ; Mutation ; Nasopharyngeal Carcinoma/genetics* ; Nasopharyngeal Neoplasms/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Prognosis ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Sirolimus ; TOR Serine-Threonine Kinases/metabolism*

Objective:To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC).Methods:Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period.Results:Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression ( HR=2.87,95% CI:0.92~8.91, P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others ( HR=8.61,95% CI:1.38~53.73, P=0.021). Conclusion:SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

Objective: To analyze the differentially expressed genes related to the chemosensitivity with the TPF regimen for hypopharyngeal squamous cell carcinoma and to measure potential functional targeting genes expressions. Methods: Twenty-nine patients with primary hypopharyngeal cancer who underwent induction chemotherapy with TPF from January 2013 to December 2017 in Beijing Tongren Hospital were enrolled for microarray analysis, including 28 males and 1 female, aged from 43 to 73 years old. Among them, 16 patients were sensitive to chemotherapy while 13 patients were non-sensitive. Illumina Human HT-12 Bead Chip was applied to analyze the gene expressions and online bioinformatics analysis was used to analyze the differentially expressed genes. Reverse transcription and quantitative real-time PCR (RT-qPCR) was used to measure the mRNA expression of potential functional genes of TPF induction chemotherapy in 43 samples, 29 from original patients and 14 from additional patients. Graphpad prism 7.0 software was used for statistical analysis. Results: A total of 1 381 significantly differentially expressed genes were screened out. By GO analysis, up-regulated genes included sequestering in extracellular matrix, chemokine receptor binding and potassium channel regulator activity; down-regulated genes included regulation of angiogenesis, calcium ion binding and natural killer cell activation involved in immune response. With KEGG database analysis, down-regulated pathways included ECM-receptor interaction and peroxisome and up-regulated pathways included Glutathione metabolism and PPAR signaling pathway. The expressions of CD44 and IL-6R were significantly different and appeared biologically significant. CD44 was significantly upregulated in insensitive tissues (0.54±0.06) compared with sensitive tissues (0.33±0.04)(P<0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (P<0.01). Conclusion CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.

BACKGROUND: How to regulate the secretion of vascular endothelial growth factor from dental pulp stem cells is of great significance for promoting dental pulp regeneration by dental pulp stem cells, especially promoting dentinogenesis, dental pulp angiogenesis and neurogenesis. OBJECTIVE: To review the factors affecting the secretion of vascular endothelial growth factor from dental pulp stem cells, providing ideas for pulp regeneration and other clinical applications. METHODS: We searched the articles in PubMed, CNKI, WanFang databases with the keywords of “vascular endothelial growth factor; dental pulp stem cell; dental pulp regeneration; hypoxia; inflammatory mediator; bacterial virulence factor; growth factor; material” in Chinese and English, respectively. Finally, 56 articles met the criteria for review. RESULTS AND CONCLUSION: Vascular endothelial growth factor is the most important cytokine in angiogenesis and neovasculization, which promotes the proliferation and differentiation of stem cells as well as protecting nerves and promoting neurogenesis. Dental pulp stem cells are the most important stem cells in dental pulp tissues. They are also important seed cells in pulp regeneration. Dental pulp stem cells have biological characteristics such as high proliferation, self-renewal and multi-lineage differentiation, and have certain secretory activities, which can be used as an alternative source of exogenous vascular endothelial growth factor. A variety of factors, such as hypoxia, bacterial virulence factors, inflammatory factors, growth factors and materials, are associated with the cytokine secretion activity of dental pulp stem cells, which can affect the expression and secretion of vascular endothelial growth factor in dental pulp stem cells. Therefore, increasing concern has been emphasized on the regulation of vascular endothelial growth factor ecpression and secretion in dental pulp stem cells and the better use in pulp regeneration.

Objective:To evaluate the application of computer-assisted design and three-dimensional printing technique in reconstruction of maxillary defects with individual free fibular flap.Methods:A total of 13 patients, 7 males and 6 females with age from 12 to 55 years old, underwent the reconstruction of maxillary defects after subtotal or total maxillectomy for benign or malignant tumors between January 2016 and December 2018 were reviewed. Ther were 4 cases of subtotal maxillectomy and 9 cases of total maxillectomy. Before operation, osteotomy line was planned on three-dimensional images. A three-dimensional individual resin fibula model based on mirror images of the healthy side maxilla was obtained to fabricate an anatomically adapted osteomyocutaneous fibula free flap using computer-assisted design and forming. Oral, nasal, and eye functions and facial appearance were evaluated.Results:The 13 cases were followed up for 5-40 months, all flaps were alive except one due to flap failure and all cases were tumor free confirmed by CT or MRI. Ten patients could eat normal food without nasal food return, and 3 cases had palatal fistula. Eleven cases showed good speaking functional results. All cases had normal eye positions, no cases with diplopia and loss of vision. With evaluation by VAS, an average score of 8 was obtained, and most of patients were satisfied with their postoperative facial appearances.Conclusion:Reconstruction of maxillary defects by free fibular flap designed by three-dimensional printing and computer-assisted technique not only restored oral, nasal and eye functions, but also showed satisfactory facial appearance.