With the increasing aging population, the incidence of wet age-related macular degeneration(wARMD)is gradually rising. The formation of neovascularization leads to recurrent hemorrhage in the macular region, which is one of the main causes of blindness in the elderly. Currently, the primary clinical treatment for wARMD is intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs. However, there are still some patients who have poor or no response to anti-VEGF drugs, resulting in suboptimal or ineffective clinical outcomes. Analyzing the specific influencing factors will be beneficial in guiding clinical decision-making. This article reviews the impact of factors such as advanced age, treatment duration, number of injections, characteristics of neovascular lesions, macular structure, intraocular cytokine levels, and genetics on the response to anti-VEGF therapy. In addition, recent studies have found that pericytes, as cellular components of microvascular walls, can influence the sensitivity to anti-VEGF therapy. This review summarizes the current research on the mechanisms of pericytes in poor or non-response to anti-VEGF therapy and discusses targeted strategies focusing on pericytes.

In recent years, the role of epigenetic modifications in tumorigenesis drawn more and more attention. The aberrant changes of histone modifications have been found in leukemias, whereby loss of balance in H3K9 methylation is associated closely with leukemogenesis. SUV39H1, the first described histone H3 lysine 9 methyltransferase takes part in heterochromatin formation and gene transcription regulation. It could be a new target for leukemia therapy by correcting the aberrance of H3K9 methylation, inducing the reexpression of tumor suppressor genes. This review discusses how H3K9 methylation regulating gene transcription, silencing gene expression and its association with leukemia.
Animals ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Histones ; genetics ; metabolism ; Humans ; Leukemia ; genetics ; metabolism ; Lysine ; metabolism ; Methylation

Aim: To investigate the roles of telomere and telomerase in the process of ginsenoside Rg1 protection against tert-butylhydroperoxide (t-BHP)-induced senescence in WI-38 cells. Methods: Senile WI-38 cells were induced by t-BHP in vitro. Cell ultrastructure, cell cycle assay and β-galactosidase cytochemistry staining were used to evaluate cell senescence. Terminal restriction fragment (RTF) length and telomerase activity were delected by southern blotting and PCR-ELISA, respectively. Results: t-BHP induced cell senescence with characteristics of shortenned RTF length. Pretreatment with Rg1 significantly attenuated t-BHP-induced senescence in WI-38 cells. Compared with cells treated with t-BHP alone, Rg1 pretreatment markedly decreased the shortening of RTF length and resulted in telomerase activation. Conclusion: Activation of telomerase and prolonging of RTF length might be involved in the process of ginsenoside Rg1 protection against t-BHP-induced senescence in WI-38 cells.

OBJECTIVETo explore the feasibility and clinical effect of posterior spinal canal decompression with pedicle screw fixation and reconstruction of anterior and middle vertebral column for thoracolumbar burst fractures complicated with nerve injury.

METHODSA total of 36 patients with thoracolumbar burst fractures treated from March 2011 to April 2016 were enrolled in the retrospective study. There were 20 males and 16 females, aged from 21 to 52 years old with an average of 37.6 years. All the fractures were located on a single segment, 8 cases of T11₁₁, 10 cases of T₁₂, 12 cases of L₁, 6 cases of L₂. According to thoracolumbar injury classification and severity score(TLICS) system, the score was 7 to 9 points, with an average of 7.4 points. According to the America Spine Injury Association(ASIA) grade, 4 cases were type A, 10 cases were type B, 14 cases were type C, 8 cases were type D. All the patients underwent posterior spinal canal decompression with pedicle screw fixation and reconstruction of anterior and middle vertebral column. The recovery of nerve function was evaluated by ASIA grading. The correction of kyphosis(Cobb angle), the volume change of injuried spinal canal, the change of anterior border height of injury vertebra which can be observed by X-rays;the internal fixation loosening and breakage and all the information of bone fusion were recorded.

RESULTSAll the operations were successful, the mean operative time and intraoperative blood loss were(2.8±0.3) h (2.1 to 3.5 h) and (880±120) ml(550 to 1 350 ml), respectively. All the incisions got primary healing. All the patients were followed up for 12 to 28 months with an average of 18.4 months. All the patients obtained satisfactory bone fusion. No pseudoarticulation formation was found, and there was no loosening, breakage of pedicle screws or displacement of titanium mesh. Neurological function was improved in different degree, except in one patient with grade A and another one with grade B. According to the ASIA grade, there were 1 case of type A, 1 case of type B, 7 cases of type C, 10 cases of type D and 17 cases of type E, postoperatively. At 3 days after operative, the anterior border height of injury vertebra, Cobb angle and the volume changes of injury spinal canal were obviously improved(<0.05), and there was no significant difference between postoperative at 3 days and final follow-up(>0.05).

CONCLUSIONSSpinal canal decompression with screw fixation and reconstruction of anterior and middle vertebral column through posterior midline approach is a safe and effective method in the treatment of thoracolumbar burst fractures with nerve injury, it is worthy to be popularized. It can complete the spinal canal decompression of 360 degree, reduction of fractures and reconstruction of vertebral three-column at the same time through a single posterior approach. The advantages includes less trauma, perfect decompression, good stability and etc.

Adult ; Bone Screws ; Decompression, Surgical ; Female ; Fracture Fixation, Internal ; Humans ; Lumbar Vertebrae ; injuries ; Male ; Middle Aged ; Retrospective Studies ; Spinal Canal ; Spinal Fractures ; surgery ; Thoracic Vertebrae ; injuries ; Treatment Outcome ; Young Adult

OBJECTIVE: To develop a simultaneous quantitative analysis method of four triterpenoids in Alismatis Rhizoma by multi-components by single maker (QAMS). METHODS: Four main triterpenoids (alisol A, alisol A 24-acetate, alisol B and alisol B 23-acetate) were selected as analytes to evaluate the quality of Alismatis Rhizoma. Alisol B 23-acetate was used as the internal reference standard and three relative correction factors (RCFs) to alisol B 23-acetate were calculated. These RCFs were obtained by high performance liquid chromatography coupled with diode array detector under various chromatographic conditions. Then 31 batches of Alismatis Rhizoma samples collected from different areas were determined by both external standard method (ESM) and QAMS. RESULTS: The RCFs were obtained with good reproducibility (RSD≤2.25%). No obvious differences were observed between the analysis results of QAMS method and ESM method (RSD≤3.52%). CONCLUSION: The established QAMS method is reliable and feasible for simultaneous analysis of four triterpenoids and could be used for quality control of Alismatis Rhizoma.

OBJECTIVETo explore the effect and possible mechanisms of miR-15a on growth of multiple myeloma(MM) cells.

METHODSMM cell lines (U266 and RPMI8226) were transfected by lentiviral particles. MM stable cell lines were selected and collected by flow cytometry (FCM). Proliferation of MM cells before and after miR-15a high expression was detected by CCK-8 method. Apoptosis of MM cells before and after miR-15a high expression was detected by AO/EB dying, Hoechst 33258 dying and FCM, respectively. Cell cycle of MM cells before and after miR-15a high expression was detected by FCM. The expressions of miR-15a, BMI-1 and BCL-2 mRNA of MM cells before and after miR-15a high expression were detected by real-time PCR. The expressions of BMI-1 protein of MM cells before and after miR-15a high expression were detected by Western blot.

RESULTSMM stable cell lines with miR-15a high expression was acquired. CCK-8 result showed that high expression of miR-15a could inhibit growth of MM cells (U266 and RPMI8226). AO/EB dying, Hoechst 33258 dying and FCM testing results showed that high expression of miR-15a could significantly induce apoptosis of MM cells (U266 and RPMI8226). The apoptosis rates of U266 and RPMI8226 cells in high expression group and control group were 90.52% vs 37.08% and 59.40% vs 44.17%, respectively. Meanwhile, FCM testing results showed that high expression of miR-15a could induce G1 arrest of MM cells (U266 and RPMI8226), which proportion of G1 phase were 41.50%±0.64%, 45.31%±0.77%, respectively. Real-time PCR results showed that during the growth inhibition process of MM cells caused by miR-15a high expression, the expression of BCL-2 mRNA decreased, but there was no significant changes in the expression of BMI-1 mRNA, while the expression of BMI-1 protein decreased significantly.

CONCLUSIONHigh expression of miR-15a can induce cell cycle arrest and apoptosis of MM cells, then inhibit their growth. The mechanisms may be related with the negative regulation of BMI-1 and BCL-2 genes in post-transcription level caused by miR-15a.

Apoptosis ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell Proliferation ; Humans ; MicroRNAs ; Multiple Myeloma ; RNA, Messenger ; Real-Time Polymerase Chain Reaction

[摘 要] 目的：探讨卵巢癌组织中PD-L1与唾液酸结合性免疫球蛋白样凝集素15（Siglec-15）的关系及其临床意义以及两者对卵巢癌SKOV3细胞增殖、迁移及侵袭的影响。方法：收集2017年1月至2019年12月福建医科大学附属第二医院妇科50例手术切除的卵巢癌组织和配对输卵管组织的石蜡包埋标本，采用免疫组化染色Envision法检测癌组织和输卵管组织中PD-L1和Siglec-15的表达水平，Kaplan-Meier生存曲线和Logistic回归分析PD-L1和Siglec-15表达与患者预后的关系。利用瞬时转染技术在卵巢癌细胞SKOV3中分别转染si-PD-L1和si-NC，用qPCR和WB法检测SKOV3细胞中PD-L1的表达对Siglec-15的影响，用CCK-8及Transwell法验证PD-L1及Siglec-15表达对SKOV3细胞增殖、迁移及侵袭的影响。结果：50例卵巢癌组织中，PD-L1与Siglec-15均呈高表达（50.00%与42.00%）。PD-L1表达与肿瘤病理类型、有无腹水、淋巴结转移、FIGO分期及卵巢癌复发与否具有关联（均P<0.05）；Siglec-15表达与卵巢癌患者淋巴结转移及FIGO分期具有关联（均P<0.05）。成功构建PD-L1低表达SKOV3细胞株，降低PD-L1表达可使Siglec-15表达升高。结论：PD-L1和Siglec-15在卵巢癌组织中均有较高的阳性表达率，PD-L1是卵巢癌复发的独立风险因素。PD-L1和Siglec-15两者的表达呈负相关，降低PD-L1表达可使Siglec-15表达水平升高而抑制SKOV3细胞增殖、迁移和侵袭的能力。

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.
Musa/genetics* ; Phylogeny ; Fungal Proteins ; Cell Nucleus ; Histones ; Stress, Physiological/genetics*

The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg or 150 mg•kg body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg. Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
Administration, Oral ; Anilides ; pharmacology ; Animals ; Bone Diseases, Developmental ; chemically induced ; Cell Proliferation ; drug effects ; physiology ; Female ; Frontal Bone ; abnormalities ; Hedgehog Proteins ; antagonists & inhibitors ; Limb Deformities, Congenital ; chemically induced ; Mice ; Micrognathism ; chemically induced ; Osteogenesis ; drug effects ; Pregnancy ; Pyridines ; pharmacology ; Signal Transduction ; drug effects

OBJECTIVE To compare the cost-utility of eight programmed death 1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitor combination regimens for first-line treatment of advanced non-small cell lung cancer(NSCLC) from the perspective of Chinese healthcare system. METHODS Relevant data were derived from a published network meta-analysis and randomized controlled trails, a three-state Markov model was established to analyze the cost-utility of eight immunotherapy combinations. The robustness of results were validated through sensitivity analyses and a series of scenario analyses was also conducted. RESULTS The incremental cost-utility ratio(ICUR) of the sintilizumab plus chemotherapy group and the tislelizumab plus chemotherapy group were ￥125143.88/quality adjusted life year(QALY) and ￥189609.64/QALY, respectively, which were less than the willingness-to-pay(WTP) threshold of ￥257094/QALY, and all the ICURs of other PD-1/PD-L1 inhibitor combination regimens exceeded the WTP threshold and were not economical. Scenario analyses found that even if the medical insurance reimbursement ratio reached 80%, the different combinations of pembrolizumab, nivolumab and atezolizumab were not economical. CONCLUSION Compared with other PD-1/PD-L1 inhibitor combination regimens, sintilizumab plus chemotherapy and tislelizumab plus chemotherapy have cost-utility advantages in the first-line treatment of advanced NSCLC, which can provide a certain reference for selecting a reasonable treatment plan for NSCLC patients.