Clinical outcomes of implantation of posterior chamber phakic intraocular lens for pathologic and non-pathologic myopia.

BACKGROUND: To compare the clinical outcomes of posterior chamber phakic intraocular lens (pIOL) implantation for non-pathological myopia and pathological myopia. METHODS: This retrospective case series study which were conducted in Beijing Tongren Eye Center between July 2017 and Oct 2021 comprised 192 eyes of 100 consecutive patients undergoing pIOL implantation. Eyes were divided into two groups based on having pathological myopia or not. Predictability, efficacy, safety, and adverse events were compared at 6 months after pIOL implantation. RESULTS: Our study included 86 non-pathological myopes (171 eyes, group1) and 14 pathological myopes (21eyes, group2) to analysis. The average ages were 25.5 and 33.0, respectively, and the spherical equivalent (SE) were -9.31D and -17.50D pre-operation. Six months after pIOL implantation, the SE were 0.00 and -0.50, respectively, and the refraction changes were statistically significant (P ≤ 0.05). Six months after surgery, 76.92% and 80.41% were within ± 0.50 D of the target and 92.31% and 95.88% were within ± 1.00 D. All eyes had unchanged BCVA or gained 1 or more lines in both groups and mean BCVA both improved a line 6m after operation. The efficacy index in the two groups were 0.95 and 0.88 and the safety index were 1.20, 1.33, respectively which was significantly different (P ≤ 0.05). Over the 6-month follow-up, no cataract, pigment dispersion glaucoma, pupillary block, or other vision-threatening complications happened, either. CONCLUSIONS: The pIOL performed well for the correction of both non-pathological and pathological myopia throughout the 6-month observation period. The clinical outcomes of pIOL implantation for non-pathological myopia are essentially equivalent to those for pathological myopia.

Research Progress on Glypican-3 Targeted Therapy in Hepatocellular Carcinoma / 药学实践杂志

Liver cancer is the second leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) being the most common form of primary liver cancer. Glypican-3 (GPC3) is a cell membrane proteoglycan which is rarely expressed in normal adult tissues but is specifically upregulated in HCC, which makes GPC3 a reliable target for the diagnosis and treatment of HCC. The role of GPC3 in the regulation of cancer development through Wnt, YAP, hedgehog and other signaling pathways were reviewed in this article. GPC3-targeted therapies, such as monoclonal antibodies, bispecific antibodies, tumor vaccines, immunotoxins, CAR-T cells, and photosensitizer therapy were also summarized. These treatment methods offered promising approaches for HCC treatment and future treatment strategies for HCC based on GPC3 were prospected in this paper.

Research progress on linear ubiquitin chain assembly complex and OTU deubiquitinase with linear linkage specificity in tumor / 药学实践杂志

Linear ubiquitination is an important post-translational modification that has been discovered in recent years. The linear ubiquitin chain is formed by the linkage of glycine residue of one ubiquitin protein to the methionine residue of another ubiquitin. This process is regulated by the linear ubiquitin chain assembly complex (LUBAC) and the OTU deubiquitinase with linear linkage specificity (OTULIN). Linear ubiquitination is involved in various biological processes, including immune response, inflammation, and cell apoptosis. Recent studies have shown that linear ubiquitination is closely related to the occurrence, development, and drug resistance of tumors by affecting signaling pathways such as NF-κB and Wnt/β-catenin. The research progress on the function of LUBAC and OTULIN in tumors was reviewed in this paper.

The effect of vitrectomy combined total versus fovea-sparing peeling of internal limiting membrane for myopic foveoschisis / 中华眼底病杂志

Objective:To systematically evaluate the effect of pars plana vitrectomy (PPV) combined total peeling of internal limiting membrane (ILM) versus fovea-sparing peeling of ILM for myopic foveoschisis.Methods:A evidence-based medicine study. Chinese and English as search terms for myopic foveoschisis, vitrectomy, and peeling of internal limiting membrane were used to search literature in China National Knowledge Infrastructure, Wanfang database, VIP database, PubMed of National Library of Medicine, Medline, Embase, and Cochrane Library. The high myopic macular schisis was selected as the research object, the intervention method was PPV combined with complete ILM peeling and combined with foveal preservation ILM peeling surgery clinical control study between Jan 1, 2010, and Jun 31, 2021. Incomplete or irrelevant literature and review literature were excluded. The method of Newcastle-Ottawa Scale system was used to evaluate the included literature. The literature was meta-analyzed by RevMan5.3 software. The mean difference ( MD) and a confidence interval ( CI) of 95% were used to describe the effect sizes of continuous data, fixed effects model was performed. The data including the best corrected visual acuity (BCVA), central fovea thickness (CFT), and postoperative macular hole (MH) were analyzed. Results:In those databases, 232 articles based search stratery were totally retrieved, and 10 articles (417 eyes) were finally included for meta-analysis with 245 eyes for PPV combined total peeling of ILM and 172 eyes for PPV combined fovea-sparing peeling of ILM. Meta-analysis results showed there was no significant difference in BCVA and CFT between the two groups (BCVA: MD=0.05, 95% CI 0.00-0.11; P>0.05; CFT: MD=-4.79, 95% CI -18.69-9.11, P>0.05). It was compared with the incidence of MH, the difference was statistically significant (odds ratio=5.70, 95% CI 2.22-14.61, P<0.05). Conclusion:BCVA and CFT could be improved by PPV combined total and fovea-sparing peeling of ILM for myopic foveoschisis; compared with complete ILM peeling, the incidence of MH was lower after foveal-sparing ILM peeling.

Interobserver agreement of international classification of myopic maculopathy / 中华眼底病杂志

Objective:To observe the interobserver agreement of classification of macular degeneration in severe pathological myopia (PM) by ophthalmologists with different clinical experience.Methods:A retrospective study. From January 2019 to December 2021, 171 eyes of 102 patients with severe PM macular degeneration who were examined at Eye Center of Beijing Tongren Hospital of Capital Medical University were included in the study. The clinical data such as age, gender, axial length, spherical equivalent power, fundus color photography, and optical coherence tomography (OCT) were collected in detail. Six independent ophthalmologists (A, B, C, D, E, F) classified each fundus photography based on META-PM and ATN classification of atrophy (A) system and interobserver agreement was assessed by Kappa statistics. According to the classification standard of traction (T) in the ATN classification, the OCT images were interpreted and classified, in which T0 was subdivided into retinal pigment epithelium (RPE) and choroidal thinning, choroidal neovascularization (CNV) with partial RPE and choroidal atrophy, RPE, and choroidal atrophy. Lamellar macular hole can't be classified by ATN system, which was defined as TX. Kappa ( κ) test was used to analyze the consistency of classification results between physicians A, B, C, D, E and F. κ value ≤0.4 indicates low consistency, 0.4 < κ value ≤ 0.6 indicates moderate consistency, and κ value >0.6 indicates strong consistency. Results:Among the 171 eyes of 102 cases, there were 20 males with 37 eyes (19.6%, 20/102), and 82 females with 134 eyes (80.4%, 82/102); age was 61.97±8.78 years; axial length was (30.87±1.93) mm; equivalent spherical power was (-16.56±7.00) D. Atrophy (A) classification results in META-PM classification and ATN classification, the consistency of physician A, B, C, D, E and physician F were 73.01%, 77.19%, 81.28%, 81.28%, 88.89%; κ value were 0.472, 0.538, 0.608, 0.610, 0.753, respectively. In the ATN classification, the T0, T1, T2, T3, T4, and T5 were in 109, 18, 11, 12, 9, and 8 eyes, respectively; TX was in 4 eyes.Conclusions:There are differences in the consistency of classification of severe PM macular lesions among physicians with different clinical experience, and the consistency will gradually improve with the accumulation of clinical experience.

Molecular design and biological activity analysis of antimicrobial peptide RIKL / 生物工程学报

Natural antimicrobial peptides have strong bactericidal activities. An obstacle of the development of antimicrobial peptides resides in the difficulty of developing peptides with high biocompatibility. In this study, molecular dynamics analysis was employed to assess the structural characteristics and biological activities of peptides. A (RXKY)2(YRY)2 structure was used as a template to design an antimicrobial peptide RIKL of high-efficiency and low-toxicity, where X represents Ile and Y represents Leu. The secondary structure of the antimicrobial peptide was detected by circular dichroism (CD), and the structures of RIKL in water and in POPC/POPG membrane environment were measured using molecular dynamics. The biological activity of RIKL was further studied by assessing its antimicrobial activity, hemolytic activity, eukaryotic cytotoxicity, and salt ion stability. CD results showed that RIKL presented an α-helical structure in a simulated bacterial membrane environment. Molecular dynamics simulation predicted that the secondary structure of RIKL could be partly retained in water and POPG environment, while this secondary structure was weakened in the POPC environment. Antimicrobial test suggested that RIKL had high antimicrobial activities, and the geometric mean of the Minimum Inhibitory Concentration (MIC) was 3.1 μmol/L. The hemolysis indicated that RIKL had no hemolytic activity within the detection range, and cytotoxicity test suggested the cytotoxicity of RIKL was low. Stability test showed that RIKL maintained antimicrobial activities under different pH, serum concentrations and salt environments. Based on the above results, RIKL has high cell selectivity and has the potential as a highly effective antibacterial drug.

Homo-PROTAC mediated suicide of MDM2 to treat non-small cell lung cancer

The dose-related adverse effects of MDM2‒P53 inhibitors have caused significant concern in the development of clinical safe anticancer agents. Herein we report an unprecedented homo-PROTAC strategy for more effective disruption of MDM2‒P53 interaction. The design concept is inspired by the capacity of sub-stoichiometric catalytic PROTACs enabling to degrade an unwanted protein and the dual functions of MDM2 as an E3 ubiquitin ligase and a binding protein with tumor suppressor P53. The new homo-PROTACs are designed to induce self-degradation of MDM2. The results of the investigation have shown that PROTAC