Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022) / 中国医学科学杂志(英文版)

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Choice of the treating methods of neovascular age-related macular degeneration / 中华实验眼科杂志

Neovascular age-related macular degeneration (AMD) is the main cause of vision loss in AMD patient.Now,the application of anti-vascular endothelial growth factor(VEGF) has become the preferred therapy for the treatment of neovascular AMD,and it has been proved to improve the visual acuity and reduce the blindness rate.But the formation of choroidal neovascularization (CNV) in AMD is a comprehensive and integrated pathological process.It is difficult to cure the CNV with only anti-VEGF drug for all the neovascular AMD patients.Therefore,the targeting drugs toward other signal pathway associated with CNV are being in different phases of clinical trials.Resent years,with the development of science and technology,small interference RNA(siRNA) and genome technology has been applied to treat neovascular AMD and show a potential prospect,and gene therapy and stem cell therapy are the most remarkable and predominant ways for AMD.Doubtlessly,these therapies offer novel choice for the management of neovascular AMD.

Inhibitory effect of cucurbitacin E on the proliferation of ovarian cancer cells and its mechanism / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>There are various biological activities of cucurbitacin E (CuE), including antitumor effect, anti-chemical carcino-genesis, liver protection, and enhancement of the immunity, and so on. This study was to investigate the effect of CuE on proliferation inhibition and apoptosis induction of ovarian cancer ES-2 cells, and to explore the mechanism.</p><p><b>METHODS</b>ES-2 cells were treated with different concentrations of CuE for 24, 48, and 72 h, respectively. Cell proliferation was tested by MTT assay. The morphologic changes and apoptosis were observed under inverted microscope and fluorescent microscope. Cell cycle distribution was evaluated with flow cytometry. The expression of p-STAT3 was determined by Western blot.</p><p><b>RESULTS</b>The number of ES-2 significantly decreased as the concentration of CuE increased or the time prolonged. Flow cytometry analysis showed that the ratio of ES-2 cells treated 1 micromol/L CuE for 24 h increased both in S phase [from (10.55+/-0.91)% to ( 16.31 +/- 4.61) % ] and in G(2)/M phase [from (18.53+/-1.43)% to (58.34 +/- 5.77)%], while decreased in G(1) phase [from (73.13 +/-4.70)% to (23.12 +/- 5.45)%] (P<0.05). The marked morphological changes of cell apoptosis were clearly observed in ES-2 cells treated with CuE. CuE inhibited the STAT3 phosphorylation in ES-2 cell in a dose- dependent manner.</p><p><b>CONCLUSION</b>CuE can inhibit ES-2 proliferation and induce apoptosis and cell cycle arrest, which may be related to the decreased expression of the intracellular STAT3 phosphorylation.</p>

Immunoregulatory effect of evodiamine in mice of various germlines / 中国实验血液学杂志

The aim of this study was to investigate the effect of evodiamine on the proliferation and the immune function of thymocytes and splenocyte of mice from three germlines, which were 8 weeks old masculinity BALB/c, C57BL/6 and F1 hybridization mice. Cells of thymus and spleen were harvested and prepared as unicellular suspension. Cell proliferation was detected by MTT method, while the concentration of IL-2 was detected by ELISA, mRNA levels of bcl-2 and cdk2 in cells treated with evodiamine were detected by RT-PCR, the apoptosis rate and intracellular reactive oxygen species (ROS) concentration were analyzed by FCM, and the protein levels of BCL-2, CDK2 and BAX were determined by fluorescence microscope. The results indicated that at 0.5, 0.75 and 1 micromol/L, evodiamine inhibited the proliferation and externalization of thymocytes and splenocytes stimulated with ConA (p < 0.05). At 0.75 micromol/L, evodiamine inhibited the secretion of IL-2, decreased the mRNA level of bcl-2 and cdk2, and induced apoptosis of thymocytes and splenocytes (p < 0.05). Intracellular ROS concentration increased significantly after treatment with evodiamine for 12 hours (p < 0.05). The death rate increased at a prolong period of time. After treatment with evodiamine for 24 and 48 hours, the cells were divided into two groups, one of which was negatively stained by 2 7-dichlorofluorescein (DCF), which indicated that ROS level decreased significantly in the dying cells. It is concluded that evodiamine inhibits proliferation and induces apoptosis of thymocytes and splenocytes from different germline mice, and at the same time decreases secretion of IL-2 through down-regulating bcl-2 and cdk2 levels.

Effect of small interfering RNA targeting multidrug resistance-related protein and bcl-2 on drug resistance and apoptosis of K562 and K562/ADM cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of small interfering RNA (siRNA) targeting multidrug resistance-related protein (MRP) and bcl-2 genes in modulating drug resistance and apoptosis of K562 and K562/ADM cells.</p><p><b>METHODS</b>Two siRNA constructs targeting respectively bcl-2 and MRP genes, were synthesized and transfected either alone or in combination into K562 and K562/ADM cells via lipofectamine2000. MTT assay was used to evaluate the viability of the transfected cells at 24, 48 and 72 h Post-fransfection, and RT-PCR was performed to determine the mRNA levels of bcl-2 and MRP. The effects of MRP siRNA and bcl2 siRNA on the apoptosis and the protein expression of Bcl-2 and MRP were evaluated with flow cytometry.</p><p><b>RESULTS</b>In K562/ADM cells, the IC (50) decreased from 12.81 microg/ml (ADM group) to 3.74 microg/ml (ADM+MRP siRNA group), 6.82 microg/ml (ADM+bcl2 siRNA group) and 2.51 microg/ml (ADM+MRP siRNA+bcl2 siRNA). Similarly, in K562 cells, the IC50 decreased significantly from 6.75 microg/ml (ADM) to 3.22 microg/ml (ADM+MRP siRNA), 3.56 microg/ml (ADM+bcl2 siRNA) and 1.84 microg/ml (ADM+MRP siRNA+bcl2 siRNA) (P<0.05). Flow cytometry demonstrated significantly increased apoptosis of the cells following MRP siRNA and bcl2 siRNA transfection, which also resulted in significantly decreased expressions of MRP and bcl-2 proteins (P<0.05).</p><p><b>CONCLUSION</b>Treatment with both MRP and bcl-2 siRNAs inhibits the target gene expression, and increases the drug sensitivity and apoptosis of K562 and K562/ADM cells.</p>