Itchy E3 ubiquitin-protein ligase promotes neuroblastoma progression in vitro and in vivo

[Objective] Neuroblastoma is the most common pediatric neuroendocrine tumor. Patients with high-risk neuroblastoma have poor clinical outcomes. Understanding the mechanisms underlying neuroblastoma progression could help identify potential therapeutic targets. This study aimed to explore the roles of itchy E3 ubiquitin-protein ligase (ITCH) in neuroblastoma progression using neuroblastoma cell lines and xenograft models of neuroblastoma. [Methods] ITCH-silencing or overexpressing neuroblastoma cells were established using two different human neuroblastoma cell lines, SK-N-AS and SH-SY5Y. In vitro and in vivo experiments were carried out to determine the effects of ITCH on neuroblastoma cell behaviors. The dual-luciferase reporter assay and co-transfection experiments were applied to determine the interaction of ITCH and miR-145-5p during neuroblastoma progression. [Results] In both cell lines, ITCH overexpression significantly promotes the proliferation, migration, and invasion capacities of neuroblastoma cells, while ITCH silencing with ShITCH suppressed neuroblastoma cell proliferation and induced apoptosis. Moreover, overexpression of ITCH decreased 51% and 54% the protein expressions of large tumor suppressor kinase 1 (LATS1), and inhibited 59% and 66% the phosphorylation of Yes-associated protein (YAP), concomitant with 2.02-fold and 2.56-fold increased expressions of cell proliferation marker Ki67 and 2.51-fold and 2.26-fold elevated levels of anti-apoptosis marker Bcl2 in SK-N-AS and SH-SY5Y cells, respectively. The dual-luciferase reporter assay demonstrated that ITCH interacted with miR-145-5p. Further in vitro and xenograft experiments showed that ITCH negatively affected the tumor-suppressive effect of miR-145-5p. [Conclusion] ITCH promotes neuroblastoma cell proliferation and metastasis by inhibiting LATS1 and promoting YAP nuclear translocation.

Modified three-step procedure to treat buried penis in children without previous surgery: experience in 150 cases

[Background] The buried penis has an abnormally smaller and shorter appearance. We performed a modified three-step procedure to correct the buried penis with satisfactory cosmetic results. [Methods] From May 2014 to December 2020, 150 boys, ranging in age from 2 to 7 years old (median age: 3.3 years), underwent this three-step procedure. The chief complaint was a smaller and shorter appearance of the penis. The surgical procedure consisted of three steps: complete degloving through a diamond-shaped penoscrotal incision, circumcision to remove the majority of the inner plate, and anchoring of the penopubic skin to the base of albuginea penis at the 4 and 8 o’clock positions with unabsorbable sutures. [Results] The mean operative time was 50 minutes (range from 40 to 60 minutes). The mean follow-up time was 2.8 years (range from 10 months to 6 years). There were no complications or recurrences. Good cosmetic results were achieved in all boys. [Conclusions] Our modified three-step procedure had good cosmetic results without complications. We recommend this effective surgical procedure for boys with buried penis who have no history of previous surgery.

Improve the success rate of inserting and intubating the spiral nasojejunal tube with bare hands

[Objective] To improve the success rate of spiral nasojejunal tube insertion through training of blind insertion of spiral nasojejunal tube with bare hands. [Methods] A total of 49 patients (5 of them were secondary intubation) who were admitted to the emergency department of our hospital from April 2, 2019 to June 17, 2021 needed to undergo blind hand intubation treatment with a nasal jejunal tube. The nurses who were recruited to participate in Guangdong. The enteral nutrition intubation training class hosted by the Provincial Nursing Society Critical Care Committee has been divided into two groups: the experimental group after training (n=28) and the control group before training (n=21) at the aim of comparing the success rate of one-time catheterization of patients in the two groups. [Results] The success rate of nurses' bare-handed blind insertion of the nasal jejunal tube increased from 43% to 86% (p<0.01). [Conclusion] Carrying out the training of blind insertion of nasal jejunal tube with bare hands can improve the success rate of tube placement for nurses in emergency department.

A rare case of Interstitial lung disease complicated by overlapping syndrome with obstructive ventilatory dysfunction as the first symptom

Interstitial lung disease is often a serious complication of connective tissue disease（CTD）, representing the first cause of death in CTD. However, there are few reports of SSc-RA overlap-associated interstitial pneumonia. Respiratory dysfunction as the first clinical manifestation is even rarely reported. We herein described a case of a male patient who developed significant respiratory dysfunction as the principal clinical sign for the past 6 months, plus newly developed skin thickening in bilateral upper limbs and pain and swelling of multiple joints for the past 6 weeks. Extensive immunological screening showed high titer of antinuclear antibodies(ANA), rheumatoid factor(RF), anti-cyclic peptide containing citrulline (anti-CCP)，and positive anti-Scl-70 antibody. Chest high resolution computed tomography(HRCT) was performed and hence ILD was confirmed. Pulmonary function test (PFT) revealed obstructive ventilatory dysfunction rather than restrictive ventilatory dysfunction. So bronchodilation test was performed and asthma was considered. Finally, after a multidisciplinary team (MDT) discussion, the diagnosis of asthma and ILD associated with SSc-RA overlap was established. It is important to note that CTD associated pulmonary interstitial fibrosis must be considered as the differential diagnosis of any newly diagnosed interstitial pulmonary disease. In addition, if patient with dyspnea is highly suspicious of pulmonary interstitial fibrosis, bronchodilation test is still needed to exclude asthma in order to avoid misdiagnosis.

Study on the mechanism of Jiawei Linggui Zhugan Decoction in the treatment of myelodysplastic syndrome based on network pharmacological analysis

the research method of network pharmacology is used to explore the material basis and mechanism of modified Linggui Zhugan Decoction in the treatment of myelodysplastic syndrome. Methods: the main active components of 8 traditional Chinese medicines of Jiawei Linggui Zhugan Decoction were searched through tcmsp database, and the target was predicted. The relevant targets of myelodysplastic syndrome were searched through geo database, and the common action targets were obtained by intersection of traditional Chinese medicine targets and disease targets. The core targets were selected by topological analysis with Cytoscape software. Finally, go-bp biological function enrichment and KEGG pathway analysis were carried out based on R software. Results: according to the database analysis, there were 248 active compounds and 3695 targets in the modified Linggui Zhugan decoction, of which 34 were common targets with metabolic syndrome; Through the topological analysis of common targets, 9 core targets were selected. Go-bp biological function enrichment and KEGG pathway analysis found that it can play its therapeutic role through p53, AGE-RAGE, cellular sensitivity, NF KB and other signal pathways. Conclusion: modified Linggui Zhugan decoction may play a therapeutic role through p53 signaling pathway, AGE-RAGE signaling pathway, cellular sensitivity, NF kappa B signaling pathway and cell cycle, so as to provide a new scientific basis for its clinical and basic research.

Nursing Research on Comprehensive Intervention of Pleural Reaction Undergoing Thoracentesis

Objective To explore the influence of different postures for pleural reaction in patients undergoing thoracic interventional operations. Methods The 695 patients with pleural effusion or hydro-pneumothorax underwent thoracic interventional operations (thoracentesis and thoracic catheter drainage) by ultrasound guidance from May, 2018 to February, 2021 were involved in this study. Two groups were divided in randomly，one was sitting posture group, 312 patients was preformed operations in this postures, the other group included 383 patients who were in supine or lateral positions. The pleural reaction rates of the two groups were compared. Results The pleural reaction rates were 18.5% (58/312) in sitting posture group and 2.8% (11/383) in supine group, there were statistically significant difference between the two groups. Conclusion Postures of patients can affect the occurrence of pleural reaction, supine position can reduce the incidence of pleural reaction.

An 8-lncRNA signature predicts the survival of triple-negative breast cancer patients without germline BRCA1/2 mutation

Purpose: TNBC with germline BRCA1/2 mutation (gBRCAm) have higher sensitivity to DNA damaging agents including platinum-based chemotherapy and PARP inhibitors. But the treatment of TNBC without gBRCAm remains challenging. This study aimed to develop a long non-coding RNA (lncRNA) signature of TNBC patients without gBRCAm to improve risk stratification and optimize individualized treatment. Methods: 98 TNBC patients without gBRCAm were acquired from The Cancer Genome Atlas database. The univariable Cox regression analysis and LASSO Cox regression model were applied to establish an lncRNA signature in the training cohort. Then Kaplan–Meier survival curve and time-dependent ROC curve were used to validate the prognostic ability of the signature. The qPCR assay was performed to confirm the expressions and clinicopathological correlations of two potential lncRNAs HAGLROS and TONSL-AS1 in 30 paired clinical triple-negative breast cancer samples without gBRCAm. Results: We developed an 8-lncRNA signature in the training cohort including HAGLROS, AL139002.1, AL391244.2, AP000696.1, AL391056.1, AL513304.1, TONSL-AS1 and AL031008.1. Patients with higher risk scores showed significantly worse overall survival compared to those with lower risk scores (P=0.00018 and P =0.0068 respectively). 30 paired specimens of TNBC without gBRCAm in our center showed that two potential lncRNAs HAGLROS and TONSL-AS1 were found frequently overexpressed, and significantly associated with tumor grade and invasion. Conclusion: We constructed a novel 8-lncRNA signature which significantly associated with the overall survival of TNBC patients without gBRCAm. Among those 8 lncRNAs, HAGLROS and TONSL-AS1 may be potential therapeutic targets which function needed further exploration.

Fasting Has Limited Impacts on the Result of Penicillin Allergy Skin Test: An Observation Study

Objective Penicillin allergy skin test is a common procedure in nursing care. Many patients can only do an allergy skin test on fasting due to the disease condition. However, whether or not the fasting state has any effects on the skin testing results remains unclear. Therefore, this study aimed to determine the effects of fasting on the results of penicillin allergy skin tests. Methods This observational cohort study analyzed the clinical data of 200 patients undergoing a penicillin skin test in the emergency center of The Seventh Affiliated Hospital of Sun Yat-sen University from August 1, 2020, to December 31, 2020, of which 100 cases were fasting patients and 100 were non-fasting patients. The information including gender, age, allergy, skin test results, dizziness, and gastrointestinal symptoms were collected and compared. Result Among the 200 patients, five patients (2.5%) tested positive for the penicillin-allergy skin tests. Three patients (3%) tested positive in the fasting group, while two patients (2%) in the non-fasting group tested positive (Relative Risk: 1.5; 95% Confidence Interval: 0.3055 to 7.397; P=0.65). Conclusion These data suggest that fasting may have limited impacts on the results of penicillin allergy skin tests.

Observation on the stability of rat myelosuppression model established by different doses of cyclophosphamide solution

Objective to investigate the stability of different doses of cyclophosphamide solution in establishing rat myelosuppression model. Methods In this study, 30 SD rats were randomly divided into control group (Group C) and model group (M1, M2, M3, M4). The rats in the model groups were injected with cyclophosphamide solution by intraperitoneal injection at doses of 30、40、(30+15) and (40+20) mg/kg respectively to establish a bone marrow suppression rat model. The changes of WBC, lym, Mon, GRA, RBC, Hb and PLT in peripheral blood were observed on the 1st, 5th and 13th day after modeling. Results （1）After modeling, the weight of rats in the model group was lower than that in the control group (P < 0.05). （2）On the 5th day, the levels of WBC, lym, mon and gra in the serum of each model group were lower than those before modeling(P < 0.05). The content of RBC in M1 and M2 groups was lower than that before modeling (P < 0.05), the content of Hb in M1, M2 and M3 groups was lower than that before modeling (P < 0.05), and the content of PLT in M1, M2, m3 and M4 groups was lower than that before modeling (P < 0.05). （3）On the 13th day, the levels of WBC, lym, mon and gra in M1 and M2 groups were higher than those on the 5th day, except for the GRA in M2 group.The levels of WBC and lym in m3 and M4 were lower than those in M1 and M2 (P < 0.05); The contents of RBC and Hb in M1 and M2 groups were lower than those before modeling (P < 0.05); Compared with M1 and M2, the content of Hb in m3 and M4 groups was higher (P < 0.05); The PLT content in the peripheral blood of M3 and M4 rats was higher than that of the 5th day, but lower than that of M1 and M2 groups (P < 0.05). Conclusion The improved method can maintain the stability of rat myelosuppression model.

To analyze the clinical characteristics of emergency syncope patients and explore their clinical treatment strategies

Objective To analyze the clinical characteristics of emergency syncope patients and explore the strategies in their clinical treatment. Methods Eighty-five patients with emergency syncope admitted to our hospital from January 2019 to April 2021 were reviewed. The clinical data of all patients were retrospectively analyzed. The common causes were analyzed and summarized, and the strategies in clinical treatment were proposed. Results The main causes of syncope are neuroreflex syncope, follow by cardiac syncope, cerebral syncope, orthostatic hypotension syncope, hysterical syncope and unexplained syncope. They accounted for 35.3%, 30.6%, 15.3%, 12.9%, 3.5%, and 2.4%, respectively. Conclusion Emergency department physicians should evaluate emergency syncope patients in time, identify patients as soon as possible, confirm the etiological diagnosis, and give reasonable and effective symptomatic treatment and treatment measures in order to improve the prognosis and ensure the life safety and quality of patients.