Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5 inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively analyzes the research and development process, molecular binding mechanisms, and the latest advancements in clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide valuable insights for further in-depth studies in this field.

From January 2012 to January 2017,98 patients with clavicular fractures were treated with titanium elastic intramedullary nail(TEN),including 58 males and 40 females with an average age of 14.5 years (11-18 years).The mean time from injury to surgery was 4.2 d (2-7 d).Sixty nine cases were treated by closed reduction and 29 cases by 2-3 cm incision.Constant function scores and disability of the arm shoulder and hand (DASH) scores were compared before surgery and 4 wks after surgery;Neer function scores at 3 months after surgery were compared between the injured side and unaffected side.All patients were reexamined at a mean follow-up of 6.5 months (3-8 months),and fracture union was determined by X-ray.The results showed that the bony union was ranged from 8-16 weeks with an average of 12.4 weeks.There were 4 cases with soft tissue irritation;no cases of infection,TEN broken,delayed healing were observed.The Constant score rose from 41.7±4.8 before operation to 92.6±3.2 at 4 weeks after operation (t=16.67,P＜0.01);the DASH score rose from 3.8±2.1 before operation to 15.8±1.8 at 4 weeks after operation (t=8.59,P＜0.01).There was no significant difference in Neer score at 3 months after treatment between unaffected side and injured side (98.56±2.41 vs.97.45±3.32,t=1.64,P＞0.05).The TEN was removed after showing bone healing on X-ray film.The study indicates that using TEN has advantages of less invasiveness,reliable fixation and rapid functional improvement of shoulder for treatment of clavicular fracture in young and adolescent patients.

Objective To compare clinical efficacy of inverse less invasive stabilization system (LISS) and Gamma nail in treating unstable femoral intertrochanteric fractures combined with lateral wall fractures.Methods Fifty-two patients with intertrochanteric fractures associated with lateral wall fractures followed up for at least 12 months after surgical treatment between June 2010 and June 2013 were included in this retrospective cohort study.According to the different internal fixation,the patients were assigned to inverse LISS group [16 males and 8 females;(62.5 ± 12.4)years] and Gamma nail group [17 males and 11 females;(60.4 ± 18.6)years].According to the AO classification,there were 6 patients with A2.2 type,5 A2.3 type,5 A3.1 type,6 A3.2 type and 2 A3.3 type in inverse LISS group,and there were 4 patients with A2.2 type,7 A2.3 type,9 A3.1 type,5 A3.2 type and 3 A3.3 type in Gamma nail group.Opcration time,total blood loss (intraoperaive plus occult blood loss),hospital length of stay,bone healing,time of commencing full weight-beating and complication incidence were compared between the two groups.Harris hip score was recorded postoperatively.Results All patients were followed up for 24-36 months (mean,30.2 months).Operation time in Gamma nail group was shorter than that in inverse LISS group (P ＜ 0.05),while relatively more blood loss was found in Gamma nail group(P ＜0.05).There were no significant differences in hospital length of stay and bone healing timebetween the two groups (P ＞ 0.05).Patients in Gamma nail groups started earlier full weight-bearing than inverse LISS group (P ＜0.05).Harris score was (86.1-± 12.4)points in inverse LISS group one year after operation,not significantly different from (83.3 ± 11.2) points in Gamma nail group (P ＞ 0.05).Complication of one patient with coxa vara and one bone nonunion in inverse LISS,showing no significant from one patient with screw breakage and one femoral head osteonecrosis in Gamma nail group (P ＞ 0.05).Conclusions Both techniques are effective in treatment of intertrochanteric fractures combined with lateral wall fractures and achieve similar results in function recovery.But inverse LISS is eccentric fixation,so too early weight-bearing should not be over-emphasized.