Objective:To explore the effectiveness of applying the ADDIE (analysis, design, develop, implement, evaluate) Model in clinical teaching for nursing interns in spine surgery department.Methods:Using a convenience sampling method, 44 nursing interns in the Department of Orthopedics at Peking Union Medical College Hospital were selected as the control group from July 2021 to May 2022, and were taught using traditional methods. From July 2022 to May 2023, 45 nursing interns were selected as the observation group, and a teaching team was formed to design a training program based on the five stages of the ADDIE instructional design model. This program was tailored to improve the overall clinical competence of the spinal surgery nursing interns. After training, the teaching effects were evaluated based on knowledge test scores, skills test scores, overall clinical competence, and teaching satisfaction.Results:After the training, the skills test scores in specialized nursing for the observation group were (94.87±1.10) points, higher than the control group's (93.98±1.41) points, with a statistically significant difference ( P<0.01). The observation group also scored higher than the control group in clinical judgment, organizational effectiveness, overall performance, and total score in the Mini-Clinical Evaluation Exercise, with statistically significant differences ( P<0.01). Additionally, the observation group reported higher satisfaction with the teaching plan and methods compared to the control group ( P<0.05) . Conclusions:Clinical teaching for spinal surgery nursing interns based on the ADDIE instructional design model can improve their specialized practical skills and overall clinical competence. The interns also expressed a high level of acceptance for this teaching design model.

Objective:To investigate the predictive value of serum vascular endothelial growth factor (VEGF), squamous cell carcinoma-associated antigen (SCCAg) and miRNA let-7a in lymph node metastasis and postoperative recurrence in patients with laryngeal cancer.Methods:A total of 82 patients with laryngeal cancer in the Second Central Hospital of Baoding from November 2017 to October 2019 were selected as the research subjects, including 18 cases of lymph node metastasis (metastasis group) and 64 cases of non metastasis (non metastasis group). The blood routine was tested before operation, and the baseline data, serum VEGF, SCCAg and miRNA let-7a levels were compared between the two groups. Logistic regression was used to analyze the related influencing factors of lymph node metastasis in patients with laryngeal cancer. The correlation between serum VEGF, SCCAg, miRNA let-7a levels and clinicopathological characteristics was analyzed. The receiver operating characteristic (ROC)curve was used to analyze the value of each index and the combined diagnosis of lymph node metastasis in patients with laryngeal cancer. After 1 year of follow-up, the serum VEGF, SCCAg and miRNA let-7a levels of patients with or without recurrent laryngeal cancer were compared. ROC curve was used to evaluate the value of VEGF, SCCAg, and miRNA let-7a in predicting the recurrence of laryngeal cancer.Results:There were statistically significant differences in tumor node metastasis (TNM) stage, degree of infiltration, degree of differentiation, serum VEGF, SCCAg, and miRNA let-7a levels between the metastasis group and non metastasis group (all P<0.05). Serum VEGF, SCCAg, miRNA let-7a levels in patients with laryngeal cancer were related to TNM stage, degree of infiltration and degree of differentiation (all P<0.05). The combined diagnosis of serum VEGF, SCCAg and miRNA let-7a levels in the diagnosis of lymph node metastasis in patients with laryngeal cancer showed that the diagnostic sensitivity and specificity were 88.89% and 70.31%, respectively. The serum VEGF and SCCAg levels of patients with recurrence after operation were higher than those without recurrence, and the level of miRNA let-7a was lower than those without recurrence (all P<0.05). The sensitivity and specificity of combined serum VEGF, SCCAg and miRNA LET-7a levels in predicting postoperative recurrence of laryngeal cancer were 72.97% and 91.11%, respectively. Conclusions:VEGF, SCCAg, miRNA let-7a in patients with laryngeal cancer have a certain correlation with clinicopathological characteristics, which can assist in the diagnosis of lymph node metastasis and help clinical prediction of postoperative recurrence in patients with laryngeal cancer, and provide a reference for the formulation of clinical treatment plans.

Objective:To investigate the clinical efficacy of anterior approach combined with blocking plates and screws in the management of acetabular fracture involving the quadrilateral area.Methods:A retrospective case series analysis was performed for 16 patients with acetabular fracture involving the quadrilateral area admitted to First and Second Affiliated Hospital of Guangxi Medical University from January 2017 to January 2019. There were 12 males and 4 females，with the age of 21-66 years［（45.3±10.6）years］. According to Letournel-Judet classification，there were 9 patients with bi-column fracture，6 with anterior and posterior traverse fracture and 1 with anterior column fracture. A total of 9 patients were operated via the ilioinguinal approach and 7 via the lateral-rectus approach. Reduction and fixation of the pelvis and acetabulum were performed，using 3.5 mm cortical bone screws or plates to block the internal displacement of fracture in the quadrilateral body. The incision length，operation time and intraoperative blood loss were recorded. The quality of fracture reduction was assessed according to the Matta reduction criteria at postoperative 2 days and hip function by the modified Merle D'Aubigne-Postel score at postoperative 3 months and 12 months. Postoperative complications were observed.Results:All patients were followed up for 13-24 months［（16.1±2.9）months］. The ilioinguinal approach and lateral-rectus approach showed surgical incision of 12-26 cm［（18.6±4.0）cm］and 8-15 cm［（10.7±2.3）cm］，respectively. The operation time was 107-215 minutes［（159.2±27.8）minutes］and the intraoperative blood loss was 200-2，300 ml［（853.1±489.7）ml］. According to Matta reduction criteria，the results were excellent in 9 patients and good in 7. Three months after operation，the modified Merle D'Aubigne-Postel score was 11-18 points［（15.2±2.2）points］，which showed the results were excellent in 4 patients，good in 7，fair in 4 and poor in 1，with the excellent and good rate of 69%. Twelve months after operation，the modified Merle D'Aubigne-Postel score was 13-18 points［（16.9±1.4）points］，which showed the results were excellent in 7 patients，good in 8 and fair in 1，with the excellent and good rate of 94%. The liquefaction of post-surgical incision was seen in a patient，bladder injury in a patient，lateral femoral cutaneous nerve injury in a patient，and heterotopic ossification in a patient. There was no loosening or breakage of the internal fixation.Conclusion:For acetabular fracture involving the quadrilateral area，anterior approach combined with blocking plates and screws can prevent the displacement of quadrilateral fracture and attain satisfactory reductiongood hip function recovery and few complications.

Objective:To analyze the clinical manifestation, laboratory examination, treatment and prognosis of congenital factor Ⅺ (FⅪ) deficiency.Methods:The clinical data of 80 patients with congenital FⅪ deficiency in our hospital from September 2006 to October 2020 were analyzed retrospectively.Results:Among the 80 patients, there were 33 males (41.3%) and 47 females (58.8%) , with a median age of 32 (2-66) years. Twenty-eight cases (35.0%) had bleeding events, including 11 cases of spontaneous bleeding (13.8%) , 9 cases of ecchymosis or bleeding after skin trauma (11.3%) , 9 cases of postoperative bleeding (11.3%) . Among the female patients, there were 11 cases of menorrhagia (23.4%) and 1 case of bleeding after vaginal delivery (2.1%) . Laboratory examination were characterized by prolonged activated partial thromboplastin time (APTT) , normal prothrombin time (PT) , and decreased FⅪ activity (FⅪ∶C) . Nine patients (11.3%) were tested for FⅪ gene (F11) with 11 mutations. Twenty-seven patients (33.8%) received fresh frozen plasma (FFP) treatment, 15 patients (18.8%) were received for prophylaxis with no bleeding occurred during and after operation.Conclusion:Most patients with congenital FⅪ deficiency have no or mild bleeding symptoms. There was no significant correlation between FⅪ∶C and the severity of bleeding symptoms, and there was a well consistency between FⅪ∶C and F11 homozygous or heterozygous mutation type. Prophylactic infusion of FFP can effectively reduce the risk of operative bleeding.

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

Objective:To investigate the clinical type and gene mutations, clinical manifestations, laboratory tests, diagnosis, and fibrinogen replacement therapy of congenital fibrinogen disorders.Methods:Clinical data of 146 patients with congenital fibrinogen disorders diagnosed from April 2000 to November 2020 were retrospectively analyzed.Results:Among the 146 patients, 61 (41.8%) men and 85 (58.2%) women had a median age of 33.5 years at the time of consultation. 34 patients (34.7%) were found to suffer from the disease due to bleeding symptoms, 33 patients (33.7%) due to preoperative examination. 55 patients (56.1%) had at least one bleeding symptom, and 42 patients (42.9%) had no bleeding symptoms. There is a negative correlation between fibrinogen activity concentration and bleeding ISTH-BAT score (rs=-0.412, P=0.001) . A total of 34 gene mutations were detected in 56 patients, of which 84.1% were missense mutations, and 16 new mutations were found. FGA Exon2 and FGG Exon8 mutations accounted for 71.4% of all mutation sites. Patients with afibrinogenemia were younger, with a median age of 2 (1-12) years, an ISTH-BAT score of 4, and patients with dysfibrinogenemia had significantly longer thrombin time (TT) , with a median of 28.5 (19.2-36.6) s. The 1 hour in vivo recovery (IVR) after fibrinogen infusion was (127.19±44.03) %, and the 24 hour IVR was (101.78±43.98) %. In addition to the obvious increase in the concentration of fibrinogen activity, the TT and the prothrombin time (PT) both decreased significantly, and the TT decreased more significantly, with an average decrease of 15.2% compared to the baseline after 24 hours of infusion. Conclusion:Most patients with congenital fibrinogen disorders have mild or no bleeding symptoms. Patients with afibrinogenemia have more severe symptoms. There is a negative correlation between the fibrinogen and the degree of bleeding. Genetic testing is helpful for the diagnosis of disease classification. FIB∶C/FIB∶Ag<0.7 can be used as a basis for clinical diagnosis. The TT can be used as the basis for the diagnosis of dysfibrinogenemia and the effectiveness of fibrinogen infusion.

Objective:To investigate the expression of coxsackievirus-adenovirus receptor (CAR) in thymic carcinoma and the relationship between CAR and the antitumor activity of oncolytic adenovirus H101.Methods:The expression of CAR in thymic carcinoma tissues and cells were detected by RT-qPCR and Western blot. H101 expression and virus titers in Bcap-37, MP59 and T1889 cells after infection were detected by RT-qPCR and 50% tissue culture infectious dose (TCID 50). The proliferation activity and apoptosis rates of T1889 cells infected with H101 at different multiplicity of infection (MOI) were detected by CCK-8 and flow cytometry. CAR expression in T1889 cells treated with different concentrations of trichostatin A (TSA), a histone deacetylase inhibitor, was detected. H101 expression and virus titers in the TSA-treated and H101-infected cells were detected. Cell activity was detected by CCK-8. The phosphorylation levels of MARK and ERK1/2 and the expression of CAR at protein level in TSA-treated or TSA+ TBHQ (ERK activator) treated cells were detected. Results:CAR expression at both mRNA and protein levels were significantly lower in thymic carcinoma tissues than in adjacent normal tissues ( P<0.01), and lower in MP59 and T1889 cells than in thymic epithelial cells (TEC) and Bcap-37 cells ( P<0.01). H101 expression in MP59 and T1889 cells and the titers of H101 in culture supernatants were significantly lower than those in Bcap-37 cells ( P<0.01). Compared with Bcap-37 cell, the activity of MP59 and T1889 cells was significantly increased and the apoptosis rates were significantly decreased 48 h after H101 infection ( P<0.01). The expression of CAR at both mRNA and protein levels in T1889 cells treated with different concentrations of TSA increased in a dose-dependent manner. When T1889 cells were treated with 0.25 μmol/L of TSA, the expression of H101 at mRNA level and H101 titers were significantly increased ( P<0.05); the phosphorylation levels of MAPK and ERK1/2 proteins were continuously decreased; the expression of CAR was continuously increased. Compared with the TSA treatment group, the expression of CAR at protein level in the TSA+ TBHQ treatment group decreased significantly ( P<0.01), and the p-ERK1/2/ERK1/2 ratio increased significantly ( P<0.01). Conclusions:TSA could up-regulate CAR expression in thymic carcinoma by inhibiting the MARK/ERK1/2 pathway, thereby enhancing the antitumor activity of H101.

Objective:To study the protective effect and the mechanism of esculetin on oxidative-stressed human retinal pigment epithelial cells (ARPE-19) induced by tert-butyl hydroperoxide (t-BHP).Methods:The ARPE-19 cells were divided into blank control group, model control group, 20 μmol/L esculetin group, 40 μmol/L esculetin group, 80 μmol/L esculetin group and 100 μmol/L esculetin group.The cells in the blank control group were normally cultured.The cells in the model control group were treated with 900 μmol/L t-BHP for 4 hours.The rest four groups were treated with 900 μmol/L t-BHP+ different molar concentrations of esculetin respectively for 4 hours.The cell viability of the each group was detected by MTS method.The activity of reactive oxygen species (ROS) was detected by fluorescence staining, and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) as well as the levels of malondialdehyde (MDA) of the cells from each group were measured with each corresponding assay kit, respectively.Results:The relative viabilities of the cells in the blank control group, model control group, 20 μmol/L esculetin group, 40 μmol/L esculetin group, 80 μmol/L esculetin group and 100 μmol/L esculetin group were (100.00±1.58)%, (49.19±1.06)%, (76.82±3.48)%, (103.90±1.60)%, (111.70±3.36)% and (113.40±3.08)%, respectively.There was a significant difference among the groups ( F=95.44, P<0.01). Compared with the blank control group, the viability of the cells in the model control group was decreased significantly ( P<0.01). Compared with the model control group, the cell viabilities in different concentrations of esculetin groups were increased significantly (all at P<0.01). There were significant differences between the groups in the relative value of ROS fluorescence intensity, MDA level, SOD activity, CAT activity and GSH-Px activity ( F=575.20, 40.61, 1 802.00, 41.62, 38.31; all at P<0.01). Compared with the model control group, the levels of ROS and MDA were decreased significantly, while the activities of SOD, CAT and GSH-Px were increased significantly in different concentrations of esculetin-treated groups (all at P<0.01). Conclusions:Esculetin can protect the oxidative damaged ARPE-19 cells by up-regulating the expression of antioxidant enzymes or antioxidant proteins.

Objective:To explore the pathogenesis, clinical characteristics, laboratory findings, diagnosis, treatment, and prognosis of congenital factor Ⅶ (FⅦ) deficiency.Methods:Clinical data of 43 patients with congenital FⅦ deficiency diagnosed from April 1999 to September 2019 were retrospectively analyzed.Results:There were 27 females and 16 males. Median age was 16 (1-70) years. Family history was found in 6 cases. There were 29 (67.4%) cases with bleeding symptoms, most common of which were mucocutaneous bleeding (13 cases, 30.2%) , oral bleeding (13 cases, 30.2%) , and epistaxis (9 cases, 20.9%) . Menorrhagia occurred in 11 cases (47.6% of female patients who were in fertile age) . Laboratory findings were characterized by significantly prolonged prothrombin time (PT) , normal partial thromboplastin time (APTT) , and decreased FⅦ activity (FⅦ∶C) . Ten cases received gene mutation analysis and 3 new mutations were found. Fourteen cases (32.6%) were treated with prothrombin complex concentrates (PCC) , 12 (27.9%) with fresh frozen plasma (FFP) , and 3 (7.0%) with human recombinant activated FⅦ (rFⅦa) . Twenty cases (46.5%) with no or mild bleeding symptoms did not receive any replacement therapy. Previous bleeding symptoms recurred in 5 patients (11.6%) , 8 females still had heavy menstrual bleeding, and 9 patients (20.9%) were lost to follow-up.Conclusion:Most patients with congenital FⅦ deficiency have mild or no bleeding symptoms, but have a tendency to excessive bleeding after surgery or trauma. There is no significant correlation between FⅦ∶C and severity of bleeding symptoms. Prophylaxis should be applied in patients with severe bleeding symptoms and rFⅦa is the first choice. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of the disease.

Objective To investigate the medium- and long-term effects and safty of Pipeline embolization device ( PED) for the treatment of large and giant intracranial anterior circulation aneurysms. Methods From December 2014 to December 2016,the data of 36 consecutive patients with large and giant aneurysm ( 36 large and giant intracranial anterior circulation aneurysms ) treated with PED in Donglei Brain Doctor Group were analyzed retrospectively. The diameter of the aneurysms was 12 -33 mm, (mean16.6±4.5mm),andthenecksizewas4-10mm(mean6.1±1.5mm).Eightaneurysmswere located in the carotid cavernous sinus segment,22 in the ophthalmic artery segment,5 in the internal carotid artery posterior communicating segment, and 1 in the M1 segment of middle cerebral artery. Seven aneurysms were only treated by PED,28 aneurysms were treated by PED in combination with coil embolization,and 1 aneurysm was treated by double PEDs. The modified Rankin scale ( mRS) score was used to evaluate the prognosis of the patients. Results (1) The clinical prognosis of the patients was followed up by telephone and outpatient department for 6-33 months. Twenty-five patients were followed up by DSA,23 aneurysms (92%) were occluded totally (Raymond gradeⅠ) and 2 (8％) were occluded near totally ( Raymond grade Ⅱ) . ( 2 ) Seven patients were treated with PED alone. Four patients were cured totally after 6 months follow-up,1 was occluded subtotally,2 were not cured;6 were cured in the last follow-up (33 months),and the other aneurysm was gradually reduced;17 of 28 patients treated with PED in combination with coils received DSA follow-up. They were followed up for 6-8 months. All the aneurysms were totally occluded ( Raymond grade Ⅰ) . 1 aneurysm was treated by 2 PEDs, DSA revealed micro-aneurysm-like development at 8 months after procedure. The aneurysms were basically occluded after 15-month follow-up. (3) MRI confirmed after operation that 10 patients had asymptomatic scattered spotted ischemic foci,4 had cerebral parenchymal hemorrhage,1 of them died,1 recovered well after treatment (mRS 1),and the other 2 were asymptomatic cerebral hemorrhage. The occupying effect of 24 cases disappeared, 8 had obvious improvement,and 3 did not have any obvious change. Conclusions The occlusion rate of the treatment of large and giant intracranial aneurysms with PED was high. The results of medium-term follow-up showed that the occlusion rate of PED in combination with coils in the treatment of aneurysms was higher than that of PED alone. The long-term follow-up results showed that the occlusion rate of patients treated with PED alone (including one or more) was gradually increased with time. The safety of the surgery needs to be further confirmed by a large sample study.