Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective:To observe the drainage effects of the venous and arterial perivascular and adventitial connective tissues(PACT)on edema of lower limbs in mice model, and to provide a new understanding of the drainage for the elderly lower extremity edema.Methods:Different doses of fluorescent sodium(FluoNa)were injected into the venous and arterial perivascular connective tissues in the feet and ankles of the lower limbs to create a model of lower extremity edema in mice.Then, at the level of the femoral artery and vein sheath, a stereoscopic fluorescence microscope was used to observe and record the drainage effect of vascular PACT pathways on the edema.Results:By tracking the diffusion and flowing of FluoNa in the interstitial space of ankle and foot, we found that(1)in addition to the local diffusion at the injection site, FluoNa can also flow along the venous and arterial PACT and the interstitial spaces between the corresponding vein and artery.(2)The flowing process along the vascular adventitia included transmission along the vascular long axis, and the long axis-perpendicular diffusion into the vascular peripheral tissue.(3)When low-dose and high-dose FluoNa were administered into the venous adventitia of the lower extremities, the venous PACT imaging was observed.(4)When low-dose and high-dose FluoNa were administered into the arterial adventitia of the lower extremities, the arterial PACT imaging was observed; (5)When low-dose and high-dose of FluoNa were administered into the near the arteriovenous-accompanying blood vessels, not only the venous PACT pathway and the arterial PACT pathway are imaged, but also the interstitial space between the pathway of the accompanying vein and artery was also visualized at the same time; (6)Histological analysis showed that the tissues stained by FluoNa were the venous and arterial adventitia and perivascular connective tissues.Conclusions:The interstitial fluid in lower extremity tissue edema can not only be drained by the venous or arterial PACT pathway, but also be drained through the interstitial space between the accompanying vein and artery when a large amount of the interstitial fluid accumulates.

Objective To analyze stress distributions on mandible bone and periodontal ligaments during acceleration of orthodontic tooth movement by mechanical vibration, and investigate the mechanism of static-vibration coupled loading to accelerate orthodontic tooth movement. MethodsThe finite element model including tooth, periodontal ligament, cancellous bone and cortical bone was established by Mimics，SolidWorks，Geomagic and ANSYS Workbench software. Conventional static orthodontic force and low-magnitude high-frequency mechanical vibration loads were applied to the finite element model for dynamic analysis. ResultsThe compression and tension zones of alveolar bone and periodontal tissues were identified based on Y-normal stress distribution of alveolar bone and periodontal tissues, which was periodic with the same frequency as the applied low-magnitude high-frequency vibration. The von Mises stress of alveolar bone and periodontal tissues also showed periodic changes, but the compression and tension zones of alveolar bone and periodontal tissues could not be identified based on von Mises stress distribution of alveolar bone and periodontal tissues. Conclusions In the field of orthodontics, Y-normal stress is a reasonable mechanical stimulus, and static-vibration coupled loading is an effective method for accelerating orthodontic treatment. The research findings can provide guidance for low-magnitude high-frequency mechanical vibration to accelerate orthodontic tooth movement.

Objective:To optimize the preparation technic of Chuanxiong Rhizoma with vacuum steam method, and to investigate the anti-inflammatory and analgesic activity of Chuanxiong Rhizoma decoction pieces with Central Composite Design-Response Surface Method. Methods:Taking the content of ferulic acid as the evaluation index and the moistening temperature, moistening time and vacuum time as the observation indexes, the moistening technic of Chuanxiong Rhizoma was optimized by Response Surface Method, and selected the optimized plan. The anti-inflammatory and analgesic activities of Chuanxiong Rhizoma were investigated by auricle swelling induced by xylene and writhing induced by glacial acetic acid. Results:The optimum vacuum moistening technic was that the softening temperature was 80 ℃, the softening time was 50 min and the vacuum time was 45 min. The content of ferulic acid in Chuanxiong Rhizoma produced by this technic is highand could decreased the times of wrinkle reaction induced by acetic acid in mice, prolonged the latent period, and obviously or partially inhibitied the ear swelling degree induced byxylene in rats. Conclusions:The Response Surface Method technic of Chuanxiong Rhizoma is easy to operate with high accuracy. The vacuum steam treatment was more obvious than traditional technology group. It provides reference for the subsequent production of Chuanxiong Rhizoma decoction pieces and have the certain value for its promotion and application.

Objective To establish the implant-mandible model with different design parameters, observe stress distributions on the implant and surrounding bone, and analyze the influence of different design parameters on dental implant of the mandible. Methods Eight implant models were designed based on structural characteristic parameters (implant diameter, thread depth, height of abutment through gingiva, thread shape), and assembly of the mandibular model was performed respectively. The models were applied with static 150 N vertical and oblique 45° loads, so as to analyze peak von Mises stress of the implant and bone tissues and explore the structural parameter variables of implant most sensitive to peak von Mises stress. Results The peak stress of the mandible was larger under inclined load than that under vertical load. Implant diameter was the key factor affecting the peak von Mises stress of cortical bone, while thread depth was the key factor affecting the peak von Mises stress of cancellous bone. The peak von Mises stress was also affected by the height of abutment through gingiva, but the effect was not as significant as thread depth and implant diameter. Thread shape had little effect on the peak von Mises stress of the mandible. Conclusions Different implant design parameters can affect the peak stress of different tissues of the mandible, so it is necessary to carefully consider the selection of implant parameters for personalized implants. This study can provide theoretical guidance for structural parameter design of oral implants and provide references for accurate prediction of oral implants.

Objective:To evaluate and compare the quality of life (QOL) in patients with hypopharyngeal squamous cell carcinoma after laryngeal preservation surgery and total laryngectomy.Methods:We selected parts of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the Head and Neck Module (EORTC QLQ-C30 and EORTC QLQ-H&N35) and designed the QOL questionnaire. We investigated 42 patients with hypopharyngeal squamous cell carcinoma underwent laryngeal preservation surgery and 38 patients underwent total laryngectomy by QOL questionnaire and followed up their survival.Results:The somatic function dimension, psychological function dimension, and social function dimension of patients underwent laryngeal preservation surgery were (92.46±15.71), (80.56±22.67) and (90.08±19.50), respectively, which were higher than (79.39±32.75), (68.42±25.05) and (61.84±29.55) of the total laryngectomy group ( P<0.05), while the economic dimension was not significantly different between the two groups ( P>0.05). The social function dimension (including social support and socialization, family relationship) of laryngeal preservation surgery group were (89.04±25.47) for postoperative time < 70 months and (90.94±13.28) for postoperative time ≥70 months, which were higher than (65.48±29.14) and (57.35±30.32) of the total laryngectomy group ( P<0.01). Conclusions:The somatic function dimension, psychological function and social function of patients with hypopharyngeal squamous cell carcinoma underwent laryngeal preservation surgery obtain a better QOL than patients underwent total laryngectomy. Therefore, we should improve the laryngeal function and QOL of patients under the premise of ensuring the survival rate.

Objective:To evaluate and compare the quality of life (QOL) in patients with hypopharyngeal squamous cell carcinoma after laryngeal preservation surgery and total laryngectomy.Methods:We selected parts of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the Head and Neck Module (EORTC QLQ-C30 and EORTC QLQ-H&N35) and designed the QOL questionnaire. We investigated 42 patients with hypopharyngeal squamous cell carcinoma underwent laryngeal preservation surgery and 38 patients underwent total laryngectomy by QOL questionnaire and followed up their survival.Results:The somatic function dimension, psychological function dimension, and social function dimension of patients underwent laryngeal preservation surgery were (92.46±15.71), (80.56±22.67) and (90.08±19.50), respectively, which were higher than (79.39±32.75), (68.42±25.05) and (61.84±29.55) of the total laryngectomy group ( P<0.05), while the economic dimension was not significantly different between the two groups ( P>0.05). The social function dimension (including social support and socialization, family relationship) of laryngeal preservation surgery group were (89.04±25.47) for postoperative time < 70 months and (90.94±13.28) for postoperative time ≥70 months, which were higher than (65.48±29.14) and (57.35±30.32) of the total laryngectomy group ( P<0.01). Conclusions:The somatic function dimension, psychological function and social function of patients with hypopharyngeal squamous cell carcinoma underwent laryngeal preservation surgery obtain a better QOL than patients underwent total laryngectomy. Therefore, we should improve the laryngeal function and QOL of patients under the premise of ensuring the survival rate.

Objective: To investigate the potential risk factors for the death of patients underwent gastric pull-up reconstruction following total pharyngoesophagectomy during perioperative periods. Methods: A total of 71 patients, including 64 males and 7 females, aged from 35 to 72 years old, with hypopharyngeal or cervical esophageal carcinoma, who underwent gastric pull-up reconstruction after pharyngoesophagectomy between October 2008 and October 2017, were reviewed retrospectively. Seventeen factors which may have potential influence on the mortality of patients during perioperative periods were evaluated by single factor Logistic regression analysis, and then those factors with obvious difference in statistics were further analyzed by multi-factor Logistic regression. Results: The rate of perioperative mortality was 9.9% (7/71). Single factor Logistic regression analysis indicated that the age of patients, abnormal electrocardiogram, TNM stages, alanine aminotransferase and D-Dimer changes, postoperative bleeding were risk factors for the death of patients(P values were 0.023, 0.004, 0.026, 0.021, 0.015 and 0.002, respectively). Multi-factor Logistic regression showed that postoperative bleeding and D-Dimer changes were 2 independent risk factors for perioperative death(P=0.021 and 0.047, respectively). Conclusions Many potential factors may affect the perioperative mortality of patients underwent gastric pull-up reconstruction following total pharyngoesophagectomy. Postoperative bleeding and significantly elevated D-Dimer level were independent risk factors for the death of patients, indicating poor prognosis.