[Clinical Effect of Tyrosine Kinase Inhibitors in the Treatment of P230 Chronic Myeloid Leukemia].

OBJECTIVE: To observe the curative efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of e19a2 transcript (P230) CML chronic phase (CML-CP) patients. METHODS: The clinical data of 11 P230 CML-CP patients were collected from July 2008 to December 2019. Blood routine examination, bone marrow cytology, chromosome, and BCR-ABL qualitative and quantitative tests were performed at initial diagnosis. After TKIs treatment, BCR-ABL (P230)/ABL in peripheral blood was regularly detected to evaluate molecular response by real-time quantitative PCR. RESULTS: There were 11 patients (7 males and 4 females) in chronic phase from 6 domestic hospitals enrolled, their median age was 46 years old (range from 19 to 56 years old). Among 4 patients treated with imatinib (400 mg, qd) firstly, 3 cases switched to nilotinib (400 mg, bid) and 1 case switched to dasatinib (100 mg, qd) due to failure to achieve best molecular response at the landmark time or mutation of ABL kinase. Then major molecular response (MMR) was obtained within 1 year. In addition, 5 patients were treated with nilotinib (300 mg, bid) and 2 patients with dasatinib (100 mg, qd) as first-line treatment, all of them got MMR within 6 months. CONCLUSION: For intolerance or resistance to imatinib, second-generation TKIs can enable P230 CML patients to achieve deeper molecular response, and MMR in a short time.

MicroRNA-384-3p inhibits retinal neovascularization through targeting hexokinase 2 in mice with diabetic retinopathy.

Diabetic retinopathy (DR) presents a microvascular complication of diabetes, which may contribute to visual impairment. The treatment of DR is still controversial. Accumulating studies have reported the role of microRNAs (miRs) in DR. This study aims to explore the functions of microRNA-384-3p (miR-384-3p) in retinal neovascularization by targeting hexokinase 2 (HK2) in mice with DR. A total of 43 C57BL/6 male mice were selected and divided into normal ( n = 16) and DR ( n = 27) groups. Retinal microvascular endothelial cells (RMECs) were collected from the normal and DR mice and mainly treated with a miR-384-3p mimic, a miR-384-3p inhibitor, small interfering RNA (siRNA) against HK2 and HK2 overexpression plasmids to understand the underlying regulatory mechanisms of miR-384-3p. The relationship between miR-384-3p and HK2 was determined by dual-luciferase reporter assay. The miR-384-3p expression and the mRNA and the protein expressions of HK2 and CD31 in retinal tissues and cells were evaluated using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tube formation was observed by conducting a tube formation experiment. HK2 is a target gene of miR-384-3p. The DR mice showed higher expression of HK2 and CD31 but lower expression of miR-384-3p. The miR-384-3p mimic and siRNA-HK2 reduced the expression of HK2, decreased cell proliferation and tube formation of RMECs, whereas the miR-384-3p inhibitor could reverse these trends. Our study demonstrates that overexpression of miR-384-3p inhibits retinal neovascularization in DR mice via inhibition of HK2.

Clinical outcomes of 23-gauge vitrectomy may be better than 20-gauge vitrectomy for retinal detachment repair.

OBJECTIVE: This study compared the clinical outcomes between 23-gauge (23-G) vitrectomy and 20-gauge (20-G) vitrectomy for the repair of retinal detachment (RD). METHODS: A retrospective comparative analysis of 135 RD patients was conducted between January, 2013 and September, 2014 in the Ophthalmology Department of the Affiliated Hospital of Weifang Medical College. The clinical outcomes of RD patients who underwent 23-G vitrectomy (n = 65) and 20-G vitrectomy (n = 70) were compared. A logistic regression analysis was used for prognostic factors in RD patients. A meta-analysis was performed using the comprehensive Meta-Analysis version 2.0 software. RESULTS: Baseline characteristics of RD patients between the 23-G group and the 20-G group were not significantly different (all p>0.05). The postoperative wound closure time was obviously shorter, and postoperative intraocular pressure (IOP; mmHg) and the incidence of macular holes (MH) were evidently lower in the 23-G group than in the 20-G group (all p<0.05). However, no statistical significances in the postoperative retinal reattachment rate or visual acuity improvement in the logarithm of the minimum angle of resolution (logMAR) were detected between the 23-G group and the 20-G group (both p>0.05). The meta-analysis further confirmed a shorter postoperative wound closure time, as well as a lower postoperative IOP and incidence of MH in the 23-G group than in the 20-G group (all p<0.05), while neither the postoperative retinal reattachment rate nor the visual acuity improvement in the logMAR showed statistical significance (all p>0.05). CONCLUSIONS: Our retrospective comparative study of RD surgery using 20-G or 23-G techniques revealed a shorter postoperative wound closure time, as well as a lower postoperative IOP and incidence of MH in the 23-G group than in the 20-G group, confirming the superiority of 23-G vitrectomy over 20-G vitrectomy. This study provided a better option of 23-G vitrectomy for clinically managing RD.

Two insulin receptors determine alternative wing morphs in planthoppers.

Wing polyphenism is an evolutionarily successful feature found in a wide range of insects. Long-winged morphs can fly, which allows them to escape adverse habitats and track changing resources, whereas short-winged morphs are flightless, but usually possess higher fecundity than the winged morphs. Studies on aphids, crickets and planthoppers have revealed that alternative wing morphs develop in response to various environmental cues, and that the response to these cues may be mediated by developmental hormones, although research in this area has yielded equivocal and conflicting results about exactly which hormones are involved. As it stands, the molecular mechanism underlying wing morph determination in insects has remained elusive. Here we show that two insulin receptors in the migratory brown planthopper Nilaparvata lugens, InR1 and InR2, have opposing roles in controlling long wing versus short wing development by regulating the activity of the forkhead transcription factor Foxo. InR1, acting via the phosphatidylinositol-3-OH kinase (PI(3)K)-protein kinase B (Akt) signalling cascade, leads to the long-winged morph if active and the short-winged morph if inactive. InR2, by contrast, functions as a negative regulator of the InR1-PI(3)K-Akt pathway: suppression of InR2 results in development of the long-winged morph. The brain-secreted ligand Ilp3 triggers development of long-winged morphs. Our findings provide the first evidence of a molecular basis for the regulation of wing polyphenism in insects, and they are also the first demonstration--to our knowledge--of binary control over alternative developmental outcomes, and thus deepen our understanding of the development and evolution of phenotypic plasticity.

Effect of HSP10 on apoptosis induced by testosterone in cultured mouse ovarian granulosa cells.

OBJECTIVE: To investigate the effect of heat shock protein 10 (HSP10) on apoptosis induced by testosterone in granulosa cells (GCs) of mouse ovaries in order to define the possible roles of HSP10 in ovarian pathological development of polycystic ovarian syndrome (PCOS) and hyperandrogenic conditions. STUDY DESIGN: Cultured mouse ovarian GCs were treated with testosterone (10(-5) mol/l). Apoptosis was assessed using flow cytometry, and proliferation was assessed using the MTT assay. HSP10 expression in the treated GCs was detected by real-time polymerase chain reaction (PCR). HSP10 gene was downregulated in the cultured GCs by AdCMV-H1-SiRNA/HSP10 or overexpressed by AdCMV-HSP10. PD98059 [phosphorylated ERK (p-ERK) inhibitor] was used to treat GCs to induce a high apoptosis index. Critical apoptotic factors and proliferation factors, including P-ERK, Bcl-2, Bax, caspase 9, caspase 3 and Ki67, were monitored by real-time reverse transcriptase PCR (RT-PCR) and Western blot. RESULTS: Compared with the control group, the apoptosis index was higher (p<0.05) and HSP10 expression was lower (p<0.05) in the testosterone-treated groups. In the AdCMV-H1-SiRNA/HSP10-treated group, cell viability was decreased (p<0.05) and the cell cycle was arrested at G2. Expression of p-ERK, Bcl-2 and Ki67, and the Bcl-2:Bax ratio were lower, while expression of apoptotic factors, including Bax, caspase 9 and caspase 3, was higher (p<0.05). Compared with the control group, Bcl-2 expression in the GCs that overexpressed HSP10 was increased (p<0.05), while the reduction of p-ERK and Bcl-2 and the elevation of caspase 9 and caspase 3 induced by PD98059 were significantly suppressed (p<0.05). CONCLUSIONS: Hyperandrogenic conditions induced apoptosis of mouse GCs. Testosterone may have reduced HSP10 expression in GCs, leading to reduced Bcl-2 expression and increased Bax expression.