OBJECTIVES: The aim of this study is to determine the effect of cannabinoid receptor (CB) 2 inhibitor on desmoglein 3 (DSG3) expression in HaCaT cells co-cultured with pemphigus serum. METHODS: Immunohistochemical staining was used to compare CB expression in pemphigus patients and normal individuals. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the concentration of CB2 in the serum of pemphigus patients and normal individuals. A correlation analysis was performed to examine the relationship between the serum CB2 and DSG of pemphigus patients. The CCK-8 assay was used to evaluate the inhibitory effect of AM630 on HaCaT cells, and the half-maximal inhibitory concentration (IC₅₀) value was utilized to determine the experimental concentration. Serum from normal individuals (negative control group) and pemphigus patients (pemphigus group) was co-cultured with HaCaT cells at a 1∶1 ratio. HaCaT cells cultured in complete medium were used as the control group. HaCaT cells in the pemphigus group treated with AM630 were employed as the AM630 group. Real-time polymerase chain reaction (PCR) and Western blot were conducted to assess the expression levels of CB2, DSG3, and β-catenin. Cell dissociation experiments were conducted to evaluate the effect of AM630 on the adhesion of HaCaT cells. RESULTS: Immunohistochemistry revealed significant differences in CB2 expression between pemphigus and normal mucosa (P<0.000 1), but no difference was found in CB1 expression. ELISA analysis revealed a statistically significant difference in the expression levels of CB2 in the serum between normal individuals and pemphigus patients (P<0.001). The expression of CB2 in the serum of pemphigus patients exhibited a significant positive correlation with that of DSG3 (r=0.831, P=0.003). The CCK-8 assay indicated that the IC₅₀ of AM630 on HaCaT cells was 0.55 μmol/L. Real-time PCR and Western blot showed that the expression levels of CB2 and DSG3 increased in the pemphigus group, while the expression level of β-catenin decreased compared with that in the AM630 groups (P<0.05). CONCLUSIONS CB2 is highly expressed in oral mucosal pemphigus. AM630 inhibits overexpression of CB2 and DSG3 and underexpression of β-catenin levels, which can provide new therapeutic targets for pemphigus.
Humans ; Pemphigus/pathology* ; Receptor, Cannabinoid, CB2/metabolism* ; Desmoglein 3/metabolism* ; Acantholysis/metabolism* ; Mouth Mucosa/pathology* ; HaCaT Cells ; Coculture Techniques ; beta Catenin/metabolism*

Objective: To investigate whether fibroblast growth factor 18(FGF18) can induce human gingival fibroblasts(HGFs) isolatedin vitroto differentiate into osteoblast-like cells, and to explore the mechanism of osteogenesis. Methods : HGFs were isolated, cultured and identified by tissue block method. The third generation of HGFs were divided into experimental group and control group. FGF18 and L-DMEM was added to the experimental group while L-DMEM was added to the control group.The effects of different concentrations of FGF18(0, 0.01, 0.02, 0.04, 0.06 mg/L) on proliferation of HGFs were detected by Methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay. Alkaline phosphatase(ALP) and alizarin red staining were used to detect the osteogenesis and mineralization ability of the cells after induction. RT-PCR, immunocytochemistry staining, and Western blot were used to detect the expression of genes and proteins related to osteogenesis and BMP2 in the BMP signaling pathway. Results: Compared with the control group, the experimental group could promote the proliferation of HGFs at 3, 5, 7, 9, and 11days(P<0.05),ALP activity and mineral salt deposition increased after induction at 14 and 21 days(P<0.05), and the expressions of ALP, OPN, OCN mRNA and BMP2 mRNA in BMP signaling pathway significantly increased(P<0.01). The expressions of OPN, OCN and BMP2 protein at 21 days were significantly higher than those at 14 days(P<0.01). Conclusion FGF18 can promote the proliferation of HGFs, and induce the differentiation of HGFs into functional osteoblasts. The osteogenic mechanism is related to the upregulation of BMP2.

Objective To investigate the characteristics and clinicopathology of v-raf murine sarcoma viral oncogene homolog Bl(BRAF)V600E mutations in papillary thyroid carcinoma(PTC)in Air Force flight personnel.Methods Data of cases and test results of BRAF V600E mutation were collected from Air Force aviators pathologically diagnosed with PTC.A univariate analysis of the relationship between BRAF V600E mutations and clinicopathologic features was performed.Results The overall rate of BRAF V600E mutations among 55 PTC flight crew members was 70.91％.The univariate analysis showed that the number of lymph node metastases in the BRAF V600E mutated group was larger than in the BRAF V600E unmutated group,and the proportion of BRAF V600E mutations in flight crews at intermediate risk of recurrence was higher than that in those at low risk of recurrence(P＜0.05).The presence or absence of BRAF V600E mutations did not affect the results of medical evaluation of PTC in flight personnel.Conclusion The rate of PTC BRAF V600E mutations in Air Force flight crews is similar to that of the general Chinese population.BRAF V600E mutations are associated with an increased number of lymph node metastases and risk of recurrence,and follow-up is recommended for flight personnel with PTC,especially those with BRAF V600E mutations.

Nursing skill competitions are the wind vane for clinical nursing development, and the teaching concepts, proposition forms, and evaluation systems demonstrated by competitions have a strong reference value for nursing teaching. This article introduces the knowledge selection and integration from nursing-related courses according to the problems and objectives to be solved by drawing on the STEM education concept in comprehensive nursing practical training in the context of integration of competition and education. Realistic problem scenarios can be created with clinical cases as the carrier or main line, and then the Tanner clinical judgment model is used to guide students to conduct a comprehensive analysis of cases, thereby helping students to develop clinical thinking ability and comprehensive practical skills, so as to bridge the gap between the contents learned at school and nursing work in clinical practice and help nursing students adapt to clinical practice as soon as possible.

Objective To explore the expression and clinical significance of Yes-associated protein 1(YAP1)in esophageal squamous cell carcinoma.Methods Immunohistochemical method was used to detect YAP1 expression in 439 cases of esophageal squamous cell carcinoma.The differences of YAP1 expression and clinical parameters were analyzed between YAP1 positive group and YAP1 negative group.Kaplan-Meier curve was used to analyze the influence of YAP1 expression on survival of patients.Results The positive rate of YAP1 in esophageal squamous cell carcinoma was 30.52% .The tumor invasion was deeper in YAP1 positive group(P＜0.001).Kaplan-Meier survival analysis showed that YAP1 positive patients had longer disease-free survival(DFS)and overall survival(OS)among patients surviving longer than 30 months(P＜0.05).The multivariate Cox regression analysis showed that the invasion depth of tumor was an independent factor affecting DFS(HR=1.371,95% CI 0.993-1.894,P=0.035)and OS(HR=1.489,95% CI 1.066-2.080,P=0.020).Conclusions YAP1 has a certain percentage of positive rate in esophageal squamous cell carcinoma;for patients with survival longer than 30 months,YAP1 positive indicates a better prognosis.

OBJECTIVES: This study aims to investigate the effects of tumor-stromal fibroblasts (TSFs) on the proliferation, invasion, and migration of salivary gland pleomorphic adenoma (SPA) cells in vitro. METHODS: Salivary gland pleomorphic adenoma cells (SPACs), TSFs, and peri-tumorous normal fibroblasts (NFs) were obtained by tissue primary culture and identified by immunocytochemical staining. The conditioned medium was obtained from TSF and NF in logarithmic phase. SPACs were cultured by conditioned medium and treated by TSF (group TSF-SPAC) and NF (group NF-SPAC). SPACs were used as the control group. The proliferation, invasion, and migration of the three groups of cells were detected by MTT, transwell, and scratch assays, respectively. The expression of vascular endothelial growth factor (VEGF) in the three groups was tested by enzyme linked immunosorbent assay (ELISA). RESULTS: Immunocytochemical staining showed positive vimentin expression in NF and TSF. Results also indicated the weak positive expression of α-smooth muscle actin (SMA) and fibroblast activation protein (FAP) in TSFs and the negative expression of α-SMA and FAP in NFs. MTT assay showed that cell proliferation in the TSF-SPAC group was significantly different from that in the NF-SPAC and SPAC groups (P<0.05). Cell proliferation was not different between the NF-SPAC and SPAC groups (P>0.05). Transwell and scratch assays showed no difference in cell invasion and migration among the groups (P>0.05). ELISA showed that no significant difference in VEGF expression among the three groups (P>0.05). CONCLUSIONS TSFs may be involved in SPA biological behavior by promoting the proliferation of SPACs but has no effect on the invasion and migration of SPACs in vitro. Hence, TSF may be a new therapeutic target in SPA treatment.
Humans ; Adenoma, Pleomorphic/metabolism* ; Vascular Endothelial Growth Factor A ; Culture Media, Conditioned/metabolism* ; Fibroblasts/metabolism* ; Salivary Glands/metabolism*

Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.

Objective:To analyze the risk factors and etiological characteristics of multidrug-resistant organism (MDRO) infection after traumatic brain injury, and to explore its nursing countermeasures.Methods:From January 2019 to January 2021, convenience sampling was used to select 478 patients with post-traumatic infection in the First Affiliated Hospital of Zhengzhou University as the research object. The patients' gender, age, underlying diseases, and infection types were collected, and the patients were divided into MDRO infection group ( n=69) and non-MDRO infection group ( n=409) according to whether the pathogen was MDRO. Binary Logistic regression was used to analyze the risk factors of MDRO infection. Results:Logistic regression analysis showed that cerebrovascular disease, malnutrition, history of shock, invasive operation, and combined use of antibiotics were independent risk factors for MDRO infection, and the difference was statistical ( P<0.05) . A total of 516 strains of pathogenic bacteria were detected in the infected samples of 478 patients, of which 386 were target strains, involving 73 strains of MDRO (18.91%) , including 22 strains of Staphylococcus aureus (30.14%) , 14 strains of Pseudomonas aeruginosa (19.18%) , 13 strains of Klebsiella pneumoniae (17.81%) , 11 strains of Escherichia coli (15.07%) , 10 strains of Acinetobacter baumannii (13.70%) , 3 strains of Enterococcus faecalis (4.11%) . The lower respiratory tract was the main site of infection, followed by the urinary tract, wound and upper respiratory tract. Conclusions:Combination of underlying diseases, invasive operation, and combined use of antibiotics all increase the risk of postoperative MDRO infection in patients with traumatic brain injury. Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae are common MDROs. Clinical nurses should strengthen the monitoring of the condition of patients with traumatic brain injury, do a good job of isolation protection, to prevent the occurrence of respiratory system, urinary system and wound infection in patients.

Objectives To study the clinical characteristics,diagnosis,treatment and prognosis of cancer metastases to the thyroid gland.Methods At Tianjin Medical University Cancer Hospital,from 1980 to 2016 30 patients were identified with a metastatic malignant tumor of the thyroid gland.Results Primary tumor sites were in the esophagus (26.7％),lung (16.7％),and kidney (13.3％).The median age at discovery of thyroid metastasis was 56 years old.The time lapse ranged from 0 to 108 months.There were 18 patients with metachronous metastasis with median survival of 36 months,12 patients were with synchronous metastasis,and the median survival was 8 months (P ＜ 0.01).20 patients were treated with thyroid surgery,and of which 15 patients were given post-op radiotherapy and chemotherapy.Patients who underwent thyroid resection had a median survival of 15 months,while that was 8 months in those without thyoid surgery (P ＜ 0.01).Conclusions Metastases to the thyroid gland is a rare clinical phenomenon,the prognosis of patients is mainly related to the biological behavior of primary tumors,but surgical resection and combined treatment can increase the survival rate.

Objective To evaluate the effect of nutritional risk screening and interventions on postoperative nutritional status in patients with oral cancer. Methods A total of 83 oral cancer patients with mild or moderate nutritional risk rated by patient-generated subjective global assessment(PG-SGA) from January 2015 to June 2017 were randomized into an experimental group(43 cases) and a control group (40 cases). The patients in the experimental group received 2-week nutritional intervention before the operation,while the patients in the control group received routine preoperative treatment and diet guidance. The biochemical measurements of postoperative nutritional indicators, peripheral blood immunoglobulin indicators, postoperative complications and hospital stays were compared between the two groups. Results The levels of prealbumin, retinol- binding protein, total lymphocyte count and transferrin were (218.5±34.6) mg/L, (23.5±4.3)μg/L, (1.82±0.45)×109/L, (2.07±0.63 )μg/L on the day of admission in the experimental group, and at 1 day before the operation were (237.3±36.5) mg/L, (27.7±4.8)μg/L, (2.02±0.39)×109/L, (2.43±0.54)μg/L, there was no significant difference(P<0.05). IgM, IgG, IgA at 1 day before the operation were significantly higher than those on the day of admission in the experimental group(P<0.05), and the levels of prealbumin, retinol-binding protein, total lymphocyte count,transferrin, IgM, IgG, IgA and body mass index at 8 days after the operation in the experimental group were significantly higher than those in the control group(t=1.574-3.418, P<0.05). The total rate of postoperative complications was 11.6％(5/43) in the experimental group, 30.0％(12/40) in the control group, and there was significant difference between the two groups (χ2=6.840, P<0.01). The incidence of infection-associated complications such as pneumonia and incision infection was 7.0％(3/43) in the experimental group, 20.0％(8/40) in the control group, and there was significant difference between the two groups (χ2=5.096, P<0.05). Conclusions Preoperative nutritional support can effectively improve the perioperative nutritional status,decrease postoperative complications and operative risk in esophageal cancer patients with mild or moderate nutritional risk.