Objective To explore the role and mechanism of microRNA-204(miR-204) carried by the exosomes of human umbilical cord-derived mesenchymal stem cells(hUC-MSC) in regulating the polarization of macrophages in a mouse model of myocardial ischemia-reperfusion(I/R) injury. Methods After the hUC-MSCs were isolated,cultured,and identified,their adipogenic and osteogenic differentiation capabilities were determined.The exosomes of hUC-MSCs were separated by ultracentrifugation,and the expression of CD81,CD63,tumor susceptibility gene 101(Tsg101),and calnexin in the exosomes was determined by Nanoparticle Tracking Analysis software,transmission electron microscopy,and Western blotting.Three groups(hUC-MSC,miR-204 mimic,and negative control) were designed for the determination of the expression of miR-204 in the cells and their exosomes by qRT-PCR.The C57BL/6J mice were randomly assigned into a sham operation group,an I/R group,a hUC-MSC exosomes group,a negative control group,and a miR-204 mimic group.Except the sham operation group,the I/R model was established by ligating the left anterior descending artery.The echocardiography system was employed to detect the heart function of mice.HE staining was employed to observe the pathological changes of mouse myocardium.ELISA was employed to determine the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),arginase 1(Arg-1),and IL-10 in the myocardial tissue.After the macrophages of mouse myocardial tissue were isolated,flow cytometry was employed to determine the expression of CD11c and CD206,and ELISA to measure the levels of IL-1β,TNF-α,Arg-1,and IL-10 in the macrophages. Results hUC-MSCs had adipogenic and osteogenic differentiation capabilities,and the exosomes were successfully identified.Compared with the negative control group,the miR-204 mimic group showed up-regulated expression of miR-204 in hUC-MSCs and their exosomes(P<0.001,P<0.001).Compared with the sham operation group,the modeling of I/R increased the left ventricular end-diastolic diameter(LVEDD)(P<0.001),left ventricular end-systolic diameter(LVESD)(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1β(P<0.001),TNF-α(P<0.001),and CD11c(P<0.001).Meanwhile,it lowered the left ventricular ejection fraction(LVEF)(P<0.001),left ventricular fractional shortening(LVFS)(P<0.001),Arg-1(P<0.001),IL-10(P<0.001),and CD206(P<0.001).Compared with those in the I/R group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1β(P<0.001),TNF-α(P=0.010),and CD11c(P<0.001) reduced,while LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.028),and CD206(P=0.022) increased in the hUC-MSC exosomes group.Compared with those in the negative control group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P=0.001),and the levels of IL-1β(P=0.048),TNF-α(P<0.001),and CD11c(P=0.007) reduced,while the LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.001),and CD206(P=0.001) increased in the miR-204 mimic group. Conclusion The hUC-MSC exosomes overexpressing miR-204 can inhibit the polarization of macrophages in the I/R mouse model to M1-type and promote the polarization to M2-type.
Animals ; Humans ; Mice ; Disease Models, Animal ; Exosomes/pathology* ; Interleukin-10/metabolism* ; Macrophages ; Mesenchymal Stem Cells ; Mice, Inbred C57BL ; MicroRNAs/genetics* ; Myocardial Reperfusion Injury ; Osteogenesis ; Stroke Volume ; Tumor Necrosis Factor-alpha/metabolism* ; Umbilical Cord/pathology* ; Ventricular Function, Left

ObjectiveThis study was to review the efficacy of surgical resections in different clinical situations for a better understanding of the meaning of surgery in the treatment of neuroblastoma (NB).

Data SourcesThe online database ScienceDirect (201-2018) was utilized. The search was conducted using the keywords "neuroblastoma," "neuroblastoma resection," "neuroblastoma surgery," and "high-risk neuroblastoma."

Study SelectionWe retrospectively analyzed of patients who underwent surgical resections in different clinical situations. The article included findings from selected relevant randomized controlled trials, systematic reviews, and meta-analyses or good-quality observational studies. Abstracts only, letters, and editorial notes were excluded. Full-text articles and abstracts were extracted and reviewed to identify key articles discussing surgery management of NB, which were then selected for critical analysis.

ResultsA total of 7800 English language articles were found containing references to NB (201-2018). The 163 articles were searched which were related to the surgical treatment of NB (201-2018). Through the analysis of these important articles, we found that the treatments of NB at low- and intermediate-risk groups were basically the same. High-risk patients remained controversial.

ConclusionsNB prognosis varies tremendously based on the stage and biologic features of the tumor. After reviewing the relevant literature, patients with low-risk disease are often managed with surgical resection or observation alone with tumors likely to spontaneously regress that are not causing symptoms. Intermediate patients are treated with chemotherapy with the number of cycles depending on their response as well as surgical resection of the primary tumor. High-risk patients remain controversial. Multidisciplinary intensive treatment is essential, especially for patients who received subtotal tumor resection. Minimally invasive surgery for the treatment of NBs without image-defined risk factors in low- to high-risk patients is safe and feasible and does not compromise the treatment outcome. We conclude that ≥90% resection of the primary tumor is both feasible and safe in most patients with high-risk NB. New targeted therapies are crucial to improve survival.

Brain Neoplasms ; surgery ; Humans ; Neuroblastoma ; surgery ; Neurosurgical Procedures ; methods ; Prognosis ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the role of CD4⁺CD25⁺regulatory cell (CD4⁺CD25⁺Treg) in auditory neuropathy (AN) using a rat model of autoimmune auditory neuropathy. Methods: The SD rats were immunized with P0 protein emulsified in complete Freunds adjuvant for 8 weeks. The number of CD4⁺CD25⁺Treg in peripheral blood and cochlea and the expression of Foxp3 gene in cochlea were detected respectively 2, 4, 6 and 8 weeks after the immunization with P0 protein in rats. Then CD4⁺CD25⁺Treg were transferred intravenously to the AN rats at 2, 4, 6 and 8 weeks of the immunization, respectively. The change of auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were detected, and the morphological changes in the inner ear were investigated. Results: The number of CD4⁺CD25⁺Treg in the peripheral blood of AN rats decreased gradually after 2, 4, 6 and 8 weeks of P0 protein immunization. The number of CD4⁺CD25⁺Treg in cochlea gradually increased with the prolongation of immunization time, but the expression of Foxp3 gene in cochlea gradually decreased over time. After intravenous transplantation of CD4⁺CD25⁺Treg in AN rats, the threshold of ABR response decreased, and DPOAE had no significant change. The number of spiral ganglion neurons in cochlea increased, and hair cells had no significant change under electron microscope. Conclusions: The decrease in the number and function of CD4⁺CD25⁺Treg reduces its inhibitory effect on autoimmune response and promotes the occurrence of autoimmune auditory neuropathy in AN rats. Adoptive transfer of CD4⁺CD25⁺Treg can reduce the autoimmune response and promote the recovery of autoimmune auditory neuropathy.
Animals ; Rats ; Forkhead Transcription Factors ; Myelin P0 Protein ; Rats, Sprague-Dawley ; T-Lymphocytes, Regulatory ; CD4 Antigens/immunology* ; Interleukin-2 Receptor alpha Subunit/immunology*

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5-3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.
Child ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Male ; Recombinant Proteins ; therapeutic use ; Thyrotropin ; blood ; Thyroxine ; blood

Objective: To analyze the clinical efficacy of thalidomide combined with TP regimen (taxol+cisplatin) in treatment of advanced gastric cancer. Methods: A total of 60 patients with advanced gastric cancer in the Affiliated Cancer Hospital of Zhengzhou University from February 2016 to March 2018 were enrolled. The patients were divided into two groups by using random number table method: the observation group (32 cases) taking thalidomide, oral administration 100 mg based on TP regimen before going to bed; the control group (28 cases) taking TP regimen chemotherapy only. Both groups received 75 mg/m² doses of cisplatin, intravenous infusion, 25 mg/m² per day, for 3 d. Paclitaxel dose was 150 mg/m², intravenous infusion for 1 day, 3-week was one course, and the efficacy was evaluated after at least 2 course of treatment. Results: The incidence of gastrointestinal adverse reactions including nausea and vomiting was 21.8% (7/32) in the observation group, and was 64.3% (18/28) in the control group, and the difference was statistically significant (χ ² = 11.051, P = 0.001), but there were no statistically significant differences in the incidence of morning faint, constipation, bone marrow suppression, liver and kidney injury and other adverse reactions between the two groups (all P > 0.05). The effective rates in the observation group and the control group were 43.8% (14/32) and 39.3% (11/28), respectively, and the disease control rates in the observation group and the control group were 84.4% (27/32) and 78.6% (22/28), respectively. There were no significant differences in the effective rates and the disease control rates between the two groups (χ ² = 0.122, P = 0.726; χ² = 0.336, P = 0.562). The improvement and significant improvement rate of sleeping quality, pain, Eastern Cooperative Oncology Group (ECOG) score was 71.9% (23/32), 53.1% (17/32), 56.2% (18/32), respectively in the observation group, and 17.9% (5/28), 14.3% (4/28), 21.4% (6/28), respectively in the control group, and the difference between the two groups was statistically significant (all P < 0.05). Conclusions Thalidomide combined with TP regimen in treatment of advanced gastric cancer patients can improve the efficacy of chemotherapy and the quality of life. It also has a good tolerance to side effects.

Objective: To explore the clinical characteristics, treatment strategy and prognosis of adenoid cystic carcinoma of the head and neck (ACCHN). Methods: A retrospective analysis of the clinical and follow-up treatment of 79 patients with ACCHN from June 2008 to July 2017 was conducted in the Cancer Hospital of Zhengzhou University. Results: A total of 79 ACCHN cases, including 31 males and 48 females. The age ranged from 19 to 77 (median, 52). The clinical manifestations of ACC were related to the locations of primary tumor.The mean size of the tumor was 2.6 cm (range from 1.5 to 7.7 cm). 50 of 79 patients with a definitive pathological diagnosis received surgical resection. 59 cases received chemotherapy and 62 cases received radiotherapy. With a median follow-up of 55 months, the 5-year, 10-year survival rate of these patients were 69.6% and 54.4%, respectively. Conclusions ACCHN is an uncommon neoplasm with the characteristics of epithelial nerve growth, being inclined to distant metastasis, and high early misdiagnosis rate. The clinical manifestation, imaging and pathological result are need to be combined together to diagnose ACCHN.

The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC-UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to 900 mg,and AUCdid not increase with dose escalation. The AUC,,andfor the 540 720 and 900 mg doses were not significantly different, respectively (>0.05). AUCandwere increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC,andwere considerable. Nonlinear PK relationships were found from the doses of 540-900 mg of EC-MPS.

Objective::To study the therapeutic and inflammatory effects of gentiopicroside(GPS) on adjuvant-induced arthritis (AA) rats. Method::The 36 male SD rats were randomly divided into six groups, namely the model group, GPS groups (low, medium and high dose), and the methotrexate (MTX) group, with six rats in each group. AA rats were induced through intradermal injection with 0.1 mL complete Freund's adjuvant (CFA) into the right hind paw, except the normal group. After modeling, rats in each group were treated with drugs for 7 days, once a day. The doses were 30, 60, 120 mg·kg^-1 in the GPS groups, and 0.2 mg·kg^-1 in the MTX group. The normal group and the model group were intragastrically treated with the same volume of normal saline. During the experiment, the paw thickness and paw volume of rats were recorded everyday by the digital vernier calipers and the toe volume measuring instrument. On the seventh day, X-ray and histopathological examination of the ankle joints were performed by the small animal living imaging instrument and hematoxylin eosin stain. Blood samples were collected from the abdominal aorta at the end of the experiment to determine the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum by enzyme-linked immunosorbent assay(ELISA) kits. The mRNA levels of IL-6 and TNF-α in synovial tissues were determined by Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR). Result::Compared with the normal group, the results of each index in the model group were significantly different (P<0.01). Compared with the model group, the results of paw volume and paw thickness decreased significantly (P<0.01), TNF-α level decreased significantly (P<0.01), and IL-6 and TNF-α mRNA levels decreased significantly (P<0.05, P<0.01) in drug treated groups. The results of X-ray and histopathological examinations indicated that GPS had a protective effect on the ankle joints of AA rats. Conclusion::GPS has the therapeutic effect on AA rats by inhibiting levels of proinflammatory cytokines in serum and relevant mRNA levels in synovial tissues.