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 Excessive cerebral microbleeds（CMB）are a critical risk factor for cognitive impairment in cerebral small vessel disease（CSVD），yet their neuroimaging mechanisms remain unclear. By using multivariate divergence among multi-contrast MRI features， this study constructs a morphometric inverse divergence （MIND） networks to reveal the pattern of CMB-related structural disruption at the network level and investigate the potential imaging mechanisms of cognitive impairment. Methods A total of 69 CSVD patients with CMB were enrolled as CSVD-c group， 61 patients without CMB were enrolled as CSVD-n group， and 66 healthy controls （HC） were enrolled as HC group. MIND network topology was compared between the three groups， and the correlation between network abnormalities and neuropsychological parameters was analyzed. Results At the cognitive domain level， CSVD patients showed global cognitive decline， significantly affecting multiple domains including memory，visuospatial ability， executive function， and language. Compared with the HCs， CSVD patients had reductions in MIND strength in the frontal lobe （left area 9a and right p32） and the right temporal lobe （Mβ and Pβ），as well as increases in the extent and severity of CMB. For global topology， the patients with CSVD showed significant reductions in global and local efficiency and a significant increase in shortest-path length， with significantly greater changes in the CSVD-c group； for regional topology， there was a significant reduction in nodal efficiency in right Mβ. The correlation analysis showed that global and local efficiency and shortest-path length were significantly correlated with the scores of global cognition and multiple cognitive domains. Network-based statistic further revealed diminished connectivity within the default-mode network （DMN） and between DMN and visual/sensorimotor networks in the CSVD-c group. Conclusion CMB not only exacerbate global cognitive decline in CSVD patients，but also significantly affect multiple cognitive domains including memory， visuospatial ability， executive function， and language.Characteristic network alterations， including reduced synchrony in fronto-temporal regions， impaired global network efficiency and local temporal lobe efficiency， and weakened DMN-related connectivity，may be the potential mechanisms by which CMB aggravate cognitive impairment in CSVD.

Objective:To investigate the clinical effects of acupuncture therapy on post-hemiplegia neck and shoulder pain.Methods:Eighty patients with post-stroke hemiplegia with neck and shoulder pain who received treatment in Department of Acupuncture, Massage and Physiotherapy, Zhejiang Provincial Armed Police Corps Hospital between December 2020 and June 2021 were included in this study. They were randomly assigned to undergo either conventional rehabilitation treatment and analgesic tablets (control group, n = 40) or conventional rehabilitation treatment, analgesic tablets and acupuncture therapy in combination (observation group, n = 40). Traditional Chinese medicine efficacy, western medicine efficacy, degree of neurological deficits, ability of daily living, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, traditional Chinese medicine efficacy and western Chinese medicine efficacy in the observation group were significantly higher than those in the control group (87.50% vs. 52.50%, 82.50% vs. 55.00%), and the incidence of adverse reactions in the observation group was significantly lower than that in the control group (17.50% vs. 42.50%, χ2 = 21.48, 16.33, 9.12, all P < 0.05). In the control group, National Institutes of Health Stroke Scale (NIHSS) score measured after treatment was significantly lower than that measured before treatment [(7.58 ± 1.87) points vs. (14.87 ± 1.36) points, t = -9.58, P < 0.001], and Barthel Index (BI) measured after treatment was significantly higher than that measured before treatment [(53.78 ± 1.34) points vs. (37.92 ± 1.74) points, t = 6.35, P < 0.001]. In the observation group, NIHSS score measured after treatment was significantly lower than that measured before treatment [(5.44 ± 2.11) points vs. (14.51 ± 0.34) points, t = -12.69, P < 0.001], and BI measured after treatment was significantly higher than that measured before treatment [(62.02 ± 0.68) points vs. (37.73 ± 1.58) points, t = 7.45, P < 0.05]. BI post-measurement in the observation group was significantly higher than that in the control group [(62.02 ± 0.68) points vs. (53.78 ± 1.34) points, t = 4.35, P < 0.05]; NIHSS score post-measurement in the observation group was significantly lower than that in the control group [(5.44 ± 2.11) points vs. (7.58 ± 1.87) points, t = -8.48, P < 0.05]. Conclusion:Acupuncture treatment for post-hemiplegia neck and shoulder pain can markedly reduce pain in patients, improve prognosis and increase clinical efficacy.