Objective:To investigate the key mechanism of transforming growth factor-β (TGF-β) inducing the expression of interleukin-17D (IL-17D) in lung cancer-associated fibroblast (CAF) and promoting the recruitment of myeloid-derived suppressor cells (MDSCs).Methods:C57BL/6 mice were established for B16 lung melanoma metastasis model (tumor model group), and control group was set up, 6 mice in each group. Flow cytometry (FACS) was used to detect the lung CAF and the changes of its ability to secrete IL-17D and the proportion of MDSCs in tumor mice. The changes of TGF-β level in lung tumor were examined by ELISA and quantitative real-time PCR (RT-qPCR). Lung fibroblasts were screened by FACS, and the effects of TGF-β on the secretion of IL-17D, C-C motif chemokine ligand (CCL)2 and CCL7 in fibroblasts were detected by RT-PCR. The migration of MDSCs under the condition of TGF-β stimulating fibroblasts was detected by Transwell.Results:The proportion of CAF (CD45 -CD326 -CD31 -) in the tumor model group was higher than that in the control group [(28.02±2.23)% vs. (7.35±2.14)%, t=9.956, P<0.001]. The ability of CAF to secrete IL-17D in the tumor model group was significantly higher than that in the control group [(38.27±2.93)% vs. (19.04±3.16)%, t=5.995, P=0.001]. The proportion of MDSCs in the tumor model group was significantly higher than that in the control group [(12.93±1.27)% vs. (8.21±1.40)%, t=4.804, P=0.009]. Compared with the control group, the protein and transcription levels of TGF-β in lung of the tumor model group were significantly increased [(1 685.07±135.61) ng/L vs. (1 047.98±68.50) ng/L, t=5.051, P=0.002; 2.17±0.03 vs. 1.00±0.05, t=51.237, P<0.001]. In vitro, lung fibroblasts were stimulated with different concentrations of TGF-β (0, 5 and 10 μg/L) for 24 hours, the relative expressions of IL-17D mRNA secreted by stimulated fibroblasts were 0.42±0.01, 0.67±0.01 and 0.84±0.04 respectively, the relative expressions of CCL2 mRNA in each group were 0.89±0.08, 1.08±0.04, 1.19±0.01 and CCL7 were 0.53±0.05, 0.65±0.04, 0.74±0.03 respectively. With the increase of TGF-β concentration, the expression levels of IL-17D, CCL2 and CCL7 in fibroblasts were significantly increased ( F=57.384, P<0.001; F=15.802, P=0.004; F=14.544, P=0.005). In addition, compared with the control group (0 μg/L TGF-β), fibroblasts treated with 10 μg/L TGF-β for 24 hours could promote the migration of MDSCs in spleen of tumor mice [(9.59±0.21)% vs. (2.14±0.24)%, t=6.585, P<0.001]. Conclusion:TGF-β can induce high expression of IL-17D in lung CAF, which is an important factor in promoting the expressions of CCL2 and CCL7 and the migration of MDSCs in tumor microenvironment.

Chronic myeloid leukemia (CML) is a myeloproliferative tumor whose pathogenesis is related to the BCR/ABL fusion gene. Tyrosine kinase inhibitors (TKIs) can significantly improve the survival and prognosis of CML patients. Nilotinib is effective in first-line treatment of CML patients with rapid response, deep remission and high safety. After achieving a sustained deep molecular response, it is a new therapeutic goal for CML to stop the use of nilotinib and achieve treatment-free remission. In addition, due to disease resistance and mutations, how to start new treatments after nilotinib treatment failure is worth further research.

Objective To investigate the prognostic factors relevant to acute low-tone sensorineural hearing loss (ALHL).Methods 196 adult ALHL patients,including 82 males and 114 females with mean age of (43.1 ± 14.3)years old were included.All patients received the same therapy and were evaluated the curative effect.To evaluate the impact factors on the prognosis of hearing,inclusive of age,gender,time delay before the first visit,degree of deafness,vestibular function,electrocochleogram,and the serum levels of thyroxines by SPSS 18.0 software.Results Of those 196 patients with ALHL,124 (63.3％) were recovery,5(2.6％) were excellent better,42(21.4％) were better,and 25 (12.8％) were poor,with a total effective rate of 87.2％.Among 15 (12.1％) who recurred the hearing loss,2 developed into Meniere's disease during the follow-up.The mean age of patients with poor hearing effect was significantly older than that of other patients (P ＜ 0.05).No relativity was found between gender and hearing curative effect.There existed a statistical difference in total effective rate among subjects with different histories (P ＜ 0.05).In addition,the recovery rate was significantly different between groups,i.e.,the course of disease was less than 14 days,between 14 days and 6 months,and between 6 months and 2 years (P ＜0.05).There was no statistical significance in total effective rate among different degrees of deafness (P ＞ 0.05).However,in term of the recovery rate,the difference was statistical significance (P ＜ 0.05).The recovery rate in patients with mild hearing loss was higher than that in middle or heavy hearing loss (both P ＜ 0.05).Among patients with mild deafness,the recovery rate in patients whose history was less than 3 months was significantly higher than that more than 3 months (P ＜ 0.05).For moderate deafness patients,the recovery rate in patients whose history was less than 7 days was significantly higher than that more than 1 month (P ＜ 0.05).There were statistical differences in hearing effect of 130 (66.3％) patients with abnormal vestibular function in comparison to that with normal vestibular function (x2 =15.1,P ＜ 0.05).There were 17(8.7％) patients with abnormal electrocochleogram combined with abnormal vestibular function,and the hearing effects were all poor.There were 45 (23.0％) patients with abnormal thyroxine levels in serum,which was significant higher than that in health adults of 5.9％ (x2 =7.26,P ＜ 0.01).There was no significant difference in hearing prognosis between patients with abnormal and normal thyroxine levels (x2 =2.51,P ＞ 0.05).Conclusions With respect to ALHL,the hearing effect is associated significantly with the history.The severity of hearing loss is negative prognostic factor for hearing recovery.Age,vestibular function,and electrocochleogram might predict hearing recovery.Gender and thyroxine levels couldn't predict the hearing prognosis,although there is a high incidence rate in patients with ALHL.

Objective We aimed to determine whether blood lipid parameters were related to the severity and the prognosis of idiopathic sudden sensorineural hearing loss(ISSNHL) patients.Methods A retrospective cohort study of 258 patients with ISSNHL from December 2013 to February 2015.The distribution characteristics of lipids [total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), Non-high-density lipoprotein cholesterol (Non-HDL-C), et al] in different degree of deafness (mild, moderate, severe, and profound), hearing curve types (low frequency, high frequency, full range frequency, and completely deafness type) and prognosis of recovery (complete, partial, slight, and no recovery) were analyzed by IBM SPSS 22.0 ANOVA analysis, chi square test and multiple regression analysis.Results TG level in mild hearing loss group was significantly lower than that in severe and profound hearing loss group (P =0.017 and P =0.007).There were no correlation between curve types and lipid indexes (P ＞ 0.05).Non-HDL-C level was elevated in no recovery and slight recovery groups (P =0.026 and 0.021).TC levels in partial recovery group and no recovery group were significantly higher than that in the complete recovery group (P =0.049 and 0.042) ,TG was higher in slight recovery group (P =0.014).Conclusions TG has significant correlation with the severity of hearing loss.There are negative correlations between hearing recovery and Non-HDL-C, TC and TG levels.Non-HDL-C, TC and TG might be a prognostic factor for treatment outcome in ISSNHL patients.

Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.