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.

Objective:To assess the urethral mobility of normal parous women in China and explore the impacts of related risk factors on it using translabial ultrasound.Methods:Females who met the inclusion criteria in 37 tertiary hospitals from February 2017 to August 2018 were included. All women underwent standardized translabial ultrasound examination and the urethral rotation angle (URA), bladder neck position at maximum Valsalva maneuver (BNP-V) and bladder neck descent (BND) were measured. Questionnaires were used to collect basic information including age, height, weight, body mass index (BMI), past medical history, maternity history, and urinary incontinence related history. Mann-Whitney U test and multiple linear regression analysis were adopted to explore the influences of age, BMI, delivery mode and parity on normal parous women′s urethral mobility. Then, the study subjects were divided into different groups and the corresponding values of URA, BNP-V and BND were compared. Results:Compared with parous women with normal BMI and no history of vaginal delivery, those who were overweight and/or had a history of vaginal delivery were more likely to gain greater URA and BND ( P<0.05). The URA and BND were not significantly different between women with different times of cesarean sections ( P>0.05); while for women with a history of vaginal delivery, these two parameters increased with the increase of the number of transvaginal deliveries ( P<0.05). Conclusions:BMI and vaginal delivery are important risk factors for the urethral mobility of normal parous women. The urethral mobility increases with the increase of BMI and the number of vaginal deliveries.

Objective To explore the efficacy and safety of anterior cervical discectomy and fusion assisted with microscope.Methods Thirty-seven patients with cervical spondylosis were included to be retrospectively ana lyzed,including 21 males and 16 females.All these patients had accepted anterior cervical discectomy and fusion (ACDF) assisted with microscope from October,2015 to February,2018,and they were aged from 22 to 77 years old (51.5±6.2 years on the average).In these patients,30 cases were operated on single segment,6 cases were operated on double segments,and 1 case was operated on 3 segments.Among all the patients,15 patients of which (40.54％) had cervical spondylotic myelopathy and 22 patients of which (59.46％) sufferered from cervical spondylotic radicu lopathy.All the operations were performed with a conventional transverse anterior cervical incisions,an intervertebral distractor was placed.The decompression was completed under the microscope,and the fixation was performed under direct vision.Moreover,the operative time,intraoperative blood loss and surgery-related complications were recorded.Follow-up was carried out at different times,including 7 days,1 month,3 months,6 months and every year after operation.Japanese Orthopaedic Association (JOA) score was used to calculate the rate of improvement in neurological function,which can evaluate the clinical efficacy.And cervical dysfunction index (NDI) was used to assess cervical function.Results All patients in this group underwent successful decompression under the microscope.The operation time was 90-160 min,with an average of (110.67±36.42) min;The intraoperative blood loss was 20-110 ml,with an average of (36.00±29.11) ml.All patients were followed-up for 12-31 months,with an average of (15.2±4.7) months.The JOA score improved from 8.37±3.26 preoperatively to 15.96 ± 1.50 at the last follow-up,and its difference had signifi cance in statistics (t=8.592,P=0.000).Neurological function improvement rate could be graded:excellent in 31 cases and good in 6 cases,the excellent and good rate was 100％;NDI was reduced from 19.01 ± 6.47 preoperatively to 5.81 ± 2.58 at the last follow-up,with statistical significant difference (t=5.127,P=0.000).During the follow-up,1 screw was found loosened and slightly withdrawn in 1 female patient at 3 months after operation,of whom had not obvious discomfort.The patient was continuously observed and there was no screw withdrawal again.Moreover,there were no complications such as cerebrospinal fluid leakage,hoarseness and difficulty in swallowing.Conclusion Microscope-assisted ACDF can provide safe and adequate decompression without significantly extending the operation time,which is satisfactory in clinical results.Even in some cases of 1 or 2 segments of intervertebral disc nucleus prolapse,it is possible to avoid a more traumatic ACDF.And it is worthy of clinical promotion.

Objective To evaluate the effect of ultrasound-guided botulinum toxin A injection into the salivary glands in treating patients with sialorrhea attributable to brain damage.Methods Nine subjects with sialorrhea attributable to traumatic brain injury (n =5),cerebral infarction (n =3) and hypoxic ischemic encephalopathy (n =1) were recruited into the study.With the guidance of ultrasound,15 units (U) of botulinum toxin type A was injected into the highest and lowest points of the two parotid glands,and 20 U was injected into two points of both submandibular glands.The saliva flow rate and the severity and frequency of sialorrhea were recorded before the treatment and 1 week,4 weeks and 12 weeks later using the Drooling Scoring System (DSS).Results The saliva flow rate before treatment (0.49 ± 0.12 g/min) decreased significantly to 0.24 ± 0.08 g/min after 1 week,but then increased again to 0.28 ±0.12 g/min after 4 weeks and 0.34 ±0.11 g/min after 12 weeks.The average DSS severity score showed the same pattern:4.35 ± 0.48 initially 1.92 ± 0.37 after 1 week,1.92 ± 0.37 after 2 weeks and 2.32 ± 0.64 after 12 weeks.The DSS frequency score,however,remained significantly lower:3.56 ± 0.49 initially,2.01 ± 0.42 after 1 and 4 weeks and 2.28 ± 0.63 after 12 weeks.Conclusion Botulinum toxin type A can effectively improve the salivary secretion and sialorrhea attributable to brain damage.

Objective To investigate the relationship between the expression of the Smad4,TGF-?_1 and T?R II and the possible mechanisms in the development of cholangiocarcinoma. Methods Immunohistochemical SABC method was used to examine the expression of Smad4,TGF-?_1 and T?R II in 49 cases of cholangiocarcinoma and 8 nomal common bile duct.Results The expression rates of Smad4,TGF-?_1 and T?R II in cholangiocarcinoma were (40.82)%(20/49),71.43%(35/49) and 36.73%(18/49) respectively; in normal common bile duct tissues were 87.50(7/8),12.50%(1/8) and 100%(8/8) respectively. There was a significant relationship between the (expression) of TGF-?_1 and clinical stage, and tumor metastasis (P