Prevalence and associated factors of suicidal ideation among college students during the COVID-19 pandemic in China: a 3-wave repeated survey.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic, a major public health crisis, harms individuals' mental health. This 3-wave repeated survey aimed to examine the prevalence and correlates of suicidal ideation at different stages of the COVID-19 pandemic in a large sample of college students in China. METHODS: Using a repeated cross-sectional survey design, we conducted 3 online surveys of college students during the COVID-19 pandemic at 22 universities in Guandong, China. The 3 surveys were conducted during the outbreak period (T1: 3 February to 10 February 2020, N = 164,101), remission period (T2: 24 March to 3 April 2020, N = 148,384), and normalized prevention and control period (T3: 1 June to 15 June 2020, N = 159,187). Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. A range of suicide-related factors was assessed, including sociodemographic characteristics, depression, anxiety, insomnia, pre-existing mental health problems, and COVID-19-related factors. RESULTS: The prevalence of suicidal ideation was 8.5%, 11.0% and 12.6% at T1, T2, and T3, respectively. Male sex (aOR: 1.35-1.44, Ps < 0.001), poor self-perceived mental health (aOR: 2.25-2.81, Ps < 0.001), mental diseases (aOR: 1.52-2.09, P < 0.001), prior psychological counseling (aOR: 1.23-1.37, Ps < 0.01), negative perception of the risk of the COVID-19 epidemic (aOR: 1.14-1.36, Ps < 0.001), depressive symptoms (aOR: 2.51-303, Ps < 0.001) and anxiety symptoms (aOR: 1.62-101.11, Ps < 0.001) were associated with an increased risk of suicidal ideation. CONCLUSION: Suicidal ideation appeared to increase during the COVID-19 pandemic remission period among college students in China. Multiple factors, especially mental health problems, are associated with suicidal ideation. Psychosocial interventions should be implemented during and after the COVID-19 pandemic to reduce suicide risk among college students.

4-HNE induces proinflammatory cytokines of human retinal pigment epithelial cells by promoting extracellular efflux of HSP70.

Oxidative stress and subsequent chronic inflammation result in dysfunction of the retinal pigment epithelium (RPE) and represent therapeutic targets in the context of age-related macular degeneration (AMD). However, molecular mechanisms that linked oxidative stress and inflammation still unclear. As an important byproduct of oxidative stress, 4-hydroxynonenal (4-HNE) induces apoptosis and lysosome dysregulation of RPE cells. In the present study, we evaluated cytokines production of RPE cells induced by 4-HNE by using cytokine array and confirmed that 4-HNE induced IL-6, IL-1ß and TNF-α production in a concentration dependent manner. Specifically, 4-HNE also induced IL-10 and TGF-ß production in low concentration. Molecular analysis revealed that intracellular HSP70 inhibited 4-HNE-induced production of pro-inflammatory cytokines, and 4-HNE exerted proinflammatory effects in RPE cells by enhancing extracellular release of HSP70, as efflux inhibitor Methyl-ß-cyclodextrin (MBC) treatment significantly blocked the release of HSP70 and decreased IL-6 production of RPE cells induced by 4-HNE. Meanwhile, HSP70 inducer arimoclomol increased intracellular HSP70 production, but showed no influence on its extracellular level, also performed anti-inflammatory effects in 4-HNE-stimulated RPE cells. Whereas the anti-inflammatory effects of paeoniflorin, an HSP70 inducer simultaneously promoted its extracellular efflux, was lower than arimoclomol. In addition, we further confirmed that MBC exhibited synergetic effect with both paeoniflorin and arimoclomol to inhibit the production of proinflammatory cytokines induced by 4-HNE. Taken together, these results indicate that HSP70 plays a vital role in regulating inflammation of RPE cells induced by oxidative stress and might be a potential novel target for clinical treatment of AMD.

1,4-Benzoxazine-3(4H)-ones as potent inhibitors of platelet aggregation: design, synthesis and structure-activity relations.

A series of novel potentially platelet aggregation-inhibiting 1,4-benzoxazine-3(4H)-one derivatives was designed and synthesized through Smiles rearrangement, reduction and acetylation reactions. The antiaggregatory activities of the target molecules on arterial blood samples from rabbits, expressed by IC50 values (µM), were then evaluated in vitro against ADP induced platelet aggregation. The favorable IC50 values of compound 8c (IC50=8.99 µM) and 8d (IC50=8.94 µM) indicated that these two compounds were the most potent molecules among all the synthesized compounds. A detailed molecular docking study to explore the interaction of compounds 8c and 8d with GP IIb/IIIa receptor showed that they these two compounds were docked into the active site of GPIIb/IIIa receptor. These results suggest that the 1,4-benzoxazine-3(4H)-one derivatives are promising lead compounds to develop new platelet aggregation inhibitors.

Biomechanical design optimization and experimental verification of Bezier curve based two-sectional cervical pillow with variable-density cellular structure.

The fundamental function of an optimal cervical pillow is to provide sufficient support to maintain normal spinal alignment and minimize biological stress on the contact surface throughout sleep. The recent advancements in cervical pillows have mainly focused on the subjective and objective evaluations of support comfort, as well as the relationship between pillow height and cervical vertebrae posture. However, only a few studies have addressed shape design guidelines and mechanical performances of the pillows themselves. In this study, a two-sectional contour cervical pillow comprising an arc and a Bezier curve is designed to support the head and neck. The design of the arc-shaped neck section incorporates the Cobb's angle and Borden value from healthy individuals to reflect the consistency of normal cervical anatomical features. The Bezier curve-based head section takes the head length and neck depth into account as significant individual differences. Static analysis and lattice optimization are performed in ANSYS Workbench to develop a variable-density cellular structure, aimed at improving air permeability and reducing the risk of pressure ulcers associated with the cervical pillow. The rapid prototyping technique fused deposition modeling (FDM) and thermoplastic material polylactic acid (PLA) are employed for fabricating different cellular structures. The results demonstrate that the neck section experiences less stress and greater deformation in comparison to the head section, indicating good comfort and support provided by the designed cervical pillow. Additionally, the compressive, bending, and cushion properties of the 3D-printed cervical pillow with variable-density cellular structure are experimentally validated, further confirming its effectiveness.

[Effects of Pre-Transplant CONUT and Post-Transplant MRD on Prognosis of Patients with Multiple Myeloma after Auto-HSCT].

OBJECTIVE: To explore the effects of pre-transplant controlling nutritional status (CONUT) and post-transplant minimal residual disease (MRD) on prognosis of patients with multiple myeloma (MM) after autologous hematopoietic stem cell transplantation (auto-HSCT). METHODS: The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The patients were divided into Low-CONUT group (n=62) and High-CONUT group (n=17) according to whether the CONUT score was less than 5. The differences in clinical features, hematopoietic reconstruction, adverse reactions, efficacy and survival between the two groups were compared. In addition, the prognostic risk factors were analyzed and verified by time-dependent ROC curve. RESULTS: The proportions of male patients and bone marrow plasma cells>30% at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group (both P <0.05). While, there were no significant differences in hematopoietic reconstruction and adverse reactions (>grade 2) between the two groups. The complete response (CR) rate and CR+very good partial response (VGPR) rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group (both P <0.05). After 3 months of transplantation, the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group (P <0.01), but CR rate did not(P >0.05). The overall survival (OS) and progression-free survival (PFS) in Low-CONUT group were both superior to those in High-CONUT group (both P <0.05). Low CONUT score (0-4) before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS (both P <0.05), while the International Myeloma Working Group (IMWG) high-risk at initial diagnosis and lactate dehydrogenase (LDH) level>250 U/L before transplantation were only risk factors for PFS (both P <0.05). Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1- and 2-year OS and PFS, and the combined prediction was more effective. CONCLUSION: The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.

Ropivacaine combined with dexmedetomidine in ultrasound-guided axillary brachial plexus block in children, a randomized controlled trial.

OBJECTIVE: In this study, we evaluated the efficacy and safety of 1 µg/kg dexmedetomidine as an adjuvant treatment to ropivacaine in children undergoing upper limb surgeries under ultrasound-guided axillary brachial plexus blocks and general anesthesia. METHODS: We enrolled 90 children (aged 1-8 years; ASA I-II) undergoing closed reduction and internal fixation for upper extremity fractures at the Xiamen Children's Hospital and randomly assigned them to one of two groups: L (injection with 0.25% ropivacaine) or D (injection with 0.25% ropivacaine containing 1 µg/kg dexmedetomidine) using the random number table method. The main outcome indicators recorded were the facial expression, leg activity, position, crying, and Face, Legs, Activity, Cry, and Consolability (FLACC) scale scores of children after surgery and the duration of block and analgesia maintenance. The secondary outcome indicators were vital sign data at the time of ultrasound probe placement (T1), at the time of block completion (T2), prior to the beginning of surgery (T3), 5 min after the beginning of surgery (T4), and at the end of surgery (T5), as well as the time of postoperative recovery, the number of cases of remedial analgesia, and complications. RESULTS: There was no statistical difference between the two groups in terms of general data, block completion time, postoperative recovery time, and complications (P > 0.05). Compared to the L group, the D group had significantly lower FLACC scores at 6 h after surgery, as well as significantly lower systolic blood pressure, diastolic blood pressure, and heart rate values at T4 and T5, and significantly longer duration of postoperative analgesia maintenance (all P < 0.05). CONCLUSION: Dexmedetomidine (1 µg/kg) as a local anesthetic adjuvant to ropivacaine can alleviate pain at 6 h postoperatively, prolong analgesia maintenance, and reduce intraoperative blood pressure and heart rate in pediatric patients undergoing closed reduction and internal fixation for upper extremity fractures, with no obvious complications or delayed recovery. CLINICAL REGISTRY NUMBER: Registration website: www.chictr.org.cn, Registration number: ChiCTR2200065163, Registration date: October, 30, 2022.

Ecological and human health hazards of soil heavy metals after wildfire: A case study of Liangshan Yi autonomous prefecture, China.

Soil samples were collected in at different depths from the conflagration area in Liangshan Yi Autonomous Region, China, to investigate the distribution characteristics and ecological and human health risks of heavy metals after a wildfire. The samples collected comprise wildfire ash (WA) above the soil surface, ash soil (AS) 0-5 cm, and plain soil (PS) 5-15 cm below the soil surface. Additionally, reference soil (RS) was collected from a nearby unburned area at the same latitude as the conflagration area. The results showed that the concentrations of zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd) in the WA and AS were significantly higher than in reference soil (RS) (p < 0.05). Concentrations of Pb in the PS were 2.52 times higher than that in RS (17.9 mg kg-1) (p < 0.05). The AS and WA had the highest Index of potential ecological risks (RI > 600). In addition, The Cd in AS and WA contributed the most to the highest Improved nemerow index (INI) and RI with a contribution of more than 80%. The concentration of heavy metals was used to establish non-carcinogenic effects and cancer risks in humans via three exposure pathways: accident ingestion of soil, dermal contact with soil, and inhalation of soil particles. Hazard index (HI) values of each sample were all less than 1, indicating the non-carcinogenic risk was within the acceptable range and would not adversely affect the local population's health. The Cancer risk (CR) values of Cr, As, Cd, and Ni were all below 1 × 10-6, indicating that heavy metal pollution from this wildfire did not pose a cancer risk to residents.

[Clinical Study of Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival. METHODS: A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed. RESULTS: For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005). CONCLUSION: The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.

Clinical Efficacy and Safety of Foldable Capsular Vitreous Body Implant Surgery in 22 Cases of Silicone Oil-dependent Eyes.

OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of foldable capsular vitreous body (FCVB) implant surgery in silicone oil-dependent eyes. METHODS: A total of 22 participants with silicone oil-dependent eyes who received treatment with FCVB implant surgery between January 2019 and June 2020 were included in this retrospective study. The intraocular pressure (IOP), best-corrected visual acuity (BCVA), demographic data, and any recorded complications were evaluated. RESULTS: The postoperative IOP (12.73±4.20 mmHg) was significantly improved (P=0.03) compared to the preoperative IOP (10.23±3.69 mmHg) (the main endpoint). There was no significant difference (P=0.33) in the final BCVA preoperation and 3rd month postoperation (the secondary endpoint). The most common postoperative complication was hyphema. Other common postoperative complications included corneal opacity, a shallow anterior chamber, and a low IOP. CONCLUSION: FCVB implant surgery is a safe and effective method for treating silicone oil-dependent eyes; however, attention should be paid to the prevention and timely treatment of complications.

Co-infection of TYLCV and ToCV increases cathepsin B and promotes ToCV transmission by Bemisia tabaci MED.

Tomato disease is an important disease affecting agricultural production, and the combined infection of tomato chlorosis virus (ToCV) and tomato yellow leaf curl virus (TYLCV) has gradually expanded in recent years, but no effective control method has been developed to date. Both viruses are transmitted by Bemisia tabaci Mediteranean (MED). Previously, we found that after B. tabaci MED was fed on ToCV-and TYLCV-infected plants, the transmission efficiency of ToCV was significantly higher than that on plants infected only with ToCV. Therefore, we hypothesize that co-infection could enhance the transmission rates of the virus. In this study, transcriptome sequencing was performed to compare the changes of related transcription factors in B. tabaci MED co-infected with ToCV and TYLCV and infected only with ToCV. Hence, transmission experiments were carried out using B. tabaci MED to clarify the role of cathepsin in virus transmission. The gene expression level and enzyme activity of cathepsin B (Cath B) in B. tabaci MED co-infected with ToCV and TYLCV increased compared with those under ToCV infection alone. After the decrease in cathepsin activity in B. tabaci MED or cathepsin B was silenced, its ability to acquire and transmit ToCV was significantly reduced. We verified the hypothesis that the relative expression of cathepsin B was reduced, which helped reduce ToCV transmission by B. tabaci MED. Therefore, it was speculated that cathepsin has profound research significance in the control of B. tabaci MED and the spread of viral diseases.

Comparison of CEAC, BEAM and IEAC conditioning regimens followed by autologous stem cell transplantation in peripheral T-cell lymphoma patients.

Autologous stem cell transplantation (ASCT) is an important treatment for peripheral T-cell lymphoma (PTCL) patients both during front and salvage therapy. In order to explore the appropriate conditioning regiments and seek ways to improve the efficacy and safety of PTCL, we retrospectively compared the outcomes of 52 PTCL patients treated with CEAC (lomustine, etoposide, cytarabine and cyclophosphamide; n = 28), BEAM (carmustine, etoposide, cytarabine and melphalan; n = 14) and IEAC (idarubicin, etoposide, cytarabine and cyclophosphamide; n = 10) regimens followed by ASCT at our center between 2012 and 2021. Although the time of neutrophil engraftment in CEAC group was earlier than that in IEAC group (P = 0.042) and platelet infusion in BEAM group was significantly more than CEAC group (P = 0.042), there were no significant difference in platelet engraftment, hematopoietic engraftment and red blood cells infusion among the 3 groups. The transplantation related mortality rate (TRM) and the early overall response rate (ORR) was 3.8% and 85.7% respectively. The 5-year OS and PFS was 62.8% (95% CI: 54.8-70.8%) and 61.0% (95% CI: 53.1-68.9%) respectively. There was no significant difference in TRM, ORR and survival among the 3 groups. Univariate and multivariate analysis showed that high PIT score (the T cell lymphoma prognostic index, > 1) and failure to reach complete response (non-CR) at 3 months after ASCT were common risk factors for OS (P = 0.036 and 0.007) and PFS (P = 0.021 and 0.012). In conclusion, CEAC and IEAC regimen can be used as alternative conditioning regiments for ASCT in PTCL patients, and their efficacy and safety are comparable to BEAM regiment. Patients with high PIT score and non-CR early after ASCT had worse outcomes.

[Effect and mechanism of matrine on apoptosis of Raji cells].

OBJECTIVE: To invest the effect and mechanism of matrine on apoptosis of human Burkitt's lymphoma Raji cells. METHODS: Raji cells were cultured in vitro and treated by different final concentrations (0.4, 0.8, 1.6 mg/mL) of matrine or combined with SB203580 (p38 MAPK inhibitor) before matrine was added, then cocultured for 48 h, cell apoptosis rate was detected by Annexin V-FITC/PI double staining method and the P-p38 MAPK, Fas, FasL protein expresssion of Raji cells were evaluated by Western blot. RESULTS: After cells were treated by matrine (0.4, 0.8, 1.6 mg/mL), the corresponding total apoptosis rate (15.77 +/- 0.53)%, (27.88 +/- 1.52)%, (48.08 +/- 2.87)%, had statistical significance compared with SB203580 groups (11. 48 +/- 0.64)%, (19.34 +/- 0.91)%, (33.98 +/- 1.26)% (P < 0.05 or P < 0.01), and control group (8.78 +/- 0.66)% (P < 0.05 or P < 0.01). As the concentration of matrine gradually increased,the protein expresssion levels of P-p38MAPK, Fas, FasL increased, and decreased after SB203580 were added, the correlation of P-p38MAPK and Fas, FasL was obvious. CONCLUSION: Matrine can upregulation of Fas and FasL to promote the apoptosis of Raji cells, it may be related to p38MAPK Activation.

The Psychological Impact of the COVID-19 Epidemic on Guangdong College Students: The Difference Between Seeking and Not Seeking Psychological Help.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has considerably psychologically impacted Chinese college students. Several types of online mental health services were widely implemented for college students during the outbreak. This study investigated the relationship between college students' mental health status and psychological help-seeking behavior to test the phases-decision-making model (PDM). METHODS: A cross-sectional survey was conducted among college students in Guangdong Province using an online platform. In total, 4,164 students were assigned to the "counseling group" or "non-counseling group" according to whether they had sought psychological help because of the COVID-19 outbreak; the groups were matched based on age, sex, and grade. Demographics, perceived mental health, and experience with seeking psychological help were recorded. Fear, depression, and trauma were assessed by the COVID-19 Fear Screening Scale, Patient Health Questionnaire, and Impact of Event Scale-6. RESULTS: The fear, depression, and trauma scores were significantly higher in the counseling group than in the non-counseling group (P s < 0.001). Fear (OR = 1.27, p < 0.001), depression (OR = 1.02, p = 0.032), trauma (OR = 1.08, p < 0.001), poor perceived mental health status (OR = 3.61, p = 0.001), and experience with seeking psychological help (OR = 7.06, p < 0.001) increased the odds of seeking psychological help. CONCLUSION: During the COVID-19 epidemic, the rate of psychological help-seeking was still low, and college students in poor psychological condition sought psychological counseling more. Fear, depression, trauma, experience with seeking psychological help, and perceived mental health can effectively predict psychological help-seeking behavior. These findings emphasized the importance of closely monitoring college students' psychological status, providing psychological intervention, and improving the probability of seeking psychological help.

NSs, the Silencing Suppressor of Tomato Spotted Wilt Orthotospovirus, Interferes With JA-Regulated Host Terpenoids Expression to Attract Frankliniella occidentalis.

Tomato spotted wilt orthotospovirus (TSWV) causes serious crop losses worldwide and is transmitted by Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). NSs protein is the silencing suppressor of TSWV and plays an important role in virus infection, cycling, and transmission process. In this research, we investigated the influences of NSs protein on the interaction of TSWV, plants, and F. occidentalis with the transgenic Arabidopsis thaliana. Compared with the wild-type Col-0 plant, F. occidentalis showed an increased number and induced feeding behavior on transgenic Arabidopsis thaliana expressing exogenous NSs. Further analysis showed that NSs reduced the expression of terpenoids synthesis-related genes and the content of monoterpene volatiles in Arabidopsis. These monoterpene volatiles played a repellent role in respect to F. occidentalis. In addition, the expression level of plant immune-related genes and the content of the plant resistance hormone jasmonic acid (JA) in transgenic Arabidopsis were reduced. The silencing suppressor of TSWV NSs alters the emission of plant volatiles and reduces the JA-regulated plant defenses, resulting in enhanced attractiveness of plants to F. occidentalis and may increase the transmission probability of TSWV.

[Clinical Significance of Minimal Residual Disease Monitoring by Multi-parameter Flow Cytometry before Allogeneic Hematopoietic Stem Cell Transplantation for Prognosis of Acute Leukemia Patients].

OBJECTIVE: To investigate the clinical significance of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia. METHODS: 81 cases of patients with AL treated with allo-HSCT in Department of Hematology, the First Affiliated Hospital of Chongqing Medical University form July 2015 to July 2018 was selected and retorspectively analyed. of which 79 patients were in CR and two patients were in non-CR. The CR group was further divided into two groups of MRD+ and MRD- based on the MRD level prior to HSCT. RESULTS: Among 81 patients, there were statistically significant differences in the three-year overall survival(OS) (CR 82.2%: NCR 0%), cumulative relapse incidence(RI) (CR 17.7%; NCR 100%) and leukemia-free survival rate(LFS) (CR 42.3%: NCR 0%) between CR and NCR group(P<0.05). Among 79 CR patients, MRD was negative in 30 patients while positive in 49 patients, there was significant differences in the three-year overall survival between MRD- and MRD+ group. The results of univariate analysis showed that the MRD+ group showed lower LFS compared with that of MRD- group （10.5% vs 36.2%）(P＜0.001，95%CI). CONCLUSION: MRD- patients shows longer LFS as compared with that of MRD+ patients, therefore, MRD monitoring by MFC before allo-HSCT is very important for the prognosis of the AL patients.

4-HNE Induces Apoptosis of Human Retinal Pigment Epithelial Cells by Modifying HSP70.

The role of heat shock protein 70 (HSP70) in apoptosis of human retinal pigment epithelial cells (ARPE-19) induced by 4-hydroxy-2-nonenal (4-HNE) was explored. Different concentrations of 4-HNE were used to stimulate ARPE-19 cells, and apoptosis was measured by flow cytometry. The expression of apoptotic-related proteins, HSP70, X-linked inhibitor-of-apoptosis (XIAP), Bcl-2, and Bax were quantified by Western blotting. HSP70 and XIAP overexpression plasmids, or their corresponding siRNAs were transfected into ARPE-19 cells using Lipofectamine™ 2000. Co-immunoprecipitation and Western blotting were used to detect the effect of 4-HNE on the expression of HSP70 and the binding level between 4-HNE and HSP70. The results showed that 4-HNE induced late apoptosis in ARPE-19 cells, accompanied by elevated levels of 4-HNE-modified HSP70, but it did not affect HSP70 protein expression. 4-HNE-modified HSP70 down-regulated the expression of the apoptosis inhibitory protein XIAP. Overexpression of HSP70 or XIAP inhibited 4-HNE-induced apoptosis of ARPE-19 cells. It was suggested that 4-HNE could promote XIAP degradation by modification of HSP70 to induce late apoptosis of human retinal pigment epithelial cells.

Tumor Suppressor miR-184 Enhances Chemosensitivity by Directly Inhibiting SLC7A5 in Retinoblastoma.

The expression patterns and functional roles of miRNAs in retinoblastoma (RB) are poorly understood, especially those involved in chemoresistance. Here, we validated the expression pattern of 20 potential RB-suppressive miRNAs and confirmed that miR-184 is the most significantly decreased miRNA in human RB tissues, as well as chemoresistant cell line. Bioinformatic and molecular analyses revealed that SLC7A5 has three binding sites of miR-184 and significantly increased in RB tissues. miR-184 negatively correlated with SLC7A5 expression in RB tissues and mainly target position 2494-2513 of the SLC7A5 3'UTR to inhibit its expression. Furthermore, enforced expression of miR-184 reversed the oncogenic roles of SLC7A5 on proliferation, migration, and invasion of RB cells. In addition, miR-184 also enhances chemosensitivity of RB cells via inducing apoptosis and G2/M cell cycle arrest. Molecular studies revealed that miR-184-decreased phosphorylation status of known DNA damage repair sensors of the ATR/ATM pathways and induced persistent formation of γH2AX foci depend on targeting SLC7A5, leading to persistent DNA damage. Thus, targeting the miR-184/SLC7A5 pathway will provide new opportunities for drug development to reverse chemotherapeutic resistance in RB.

Application of fluorescein sodium in breast cancer brain-metastasis surgery.

OBJECTIVE: Surgical resection serves an important role in the multidisciplinary treatment of cerebral metastases (CMs). Conventional white-light, microsurgical, and circumferential stripping of CMs is standard neurosurgical procedure, but is associated with a high recurrence rate. Based on this outcome, there is an urgent need for a new surgical strategy, such as fluorescence-guided resection, for CMs, in order to achieve total removal. METHODS: A retrospective study was carried out in 38 patients clinically and pathologically diagnosed with breast cancer brain metastasis at three medical centers from May 2012 to June 2016. The study comprised group 1 (fluorescein-guided surgery) and group 2 (standard microsurgery). In group 1, 5 mg/kg of fluorescein sodium was injected intravenously after an allergy test and before general anesthesia for 17 patients. A yellow 560 filter was employed for microsurgical tumor resection. Group 2 consisted of 21 patients for whom fluorescein was not administered. RESULTS: Surgical outcomes were assessed concerning the extent of resection and Karnofsky performance status. Gross total resection was achieved in these patients, with high fluorescence markedly enhancing tumor visibility. The extent of resection had a powerful influence on performance status. Overall survival after CM was 24.1 months in patients given fluorescein and was 22.8 months in the nonfluorescein group. CONCLUSION: Fluorescein-guided surgery is a simple, safe, and practical method to resect breast cancer brain metastasis, and leads to a higher proportion of resection compared to common microsurgery. This offers a tremendous advantage when navigating a tiny tumor, and improves the quality of life of patients with CM.

Prognostic factors for olfactory groove meningioma with nasal cavity extension.

OBJECTIVES: Meningioma recurrence remains a significant issue. No study has described the relationship between the clinical features and prognosis of communicating meningioma that primarily originates from the olfactory groove. The aim of the study was to identify prognostic factors of communicating olfactory groove meningiomas that could be stratified according to their risk of recurrence. RESULTS: A Simpson grade one or two resection was achieved. Complications with cerebrospinal rhinorrhoea occurred in two patients: one required reoperation, and the other was managed successfully with external drainage of lumbar cistern. There were 5 known clinical recurrences within the median follow-up of more than 5 years. The median 5-year recurrence-free survival for patients was 88.4%. Factors such as gender, tumour size, T2 signal and the hyperostotic bone had no significant effect on recurrence-free survival. However, recurrence was activated by oedema range, hyperostosis, dural tail sign and tumor texture (p < 0.05). Interestingly, female patients with the disease were younger than males at diagnosis, and the difference was statistically significant ( p = 0.013). CONCLUSIONS: Based on these features of communicating olfactory groove meningiomas, different strategies may be adopted for the follow-up and subsequent treatment. Due to the relatively uncommon incidence, more investigations into the clinical behaviour of this entity are crucial. PATIENTS AND METHODS: A retrospective study of 43 patients harbouring olfactory groove meningiomas invading the ethmoid or nasal cavity was conducted at three medical centers from 2000 to 2010. The records were reviewed for clinical presentations, imaging studies, surgical observation, histological features and follow-up.

Safety and efficacy of transcatheter arterial chemoembolization with embospheres in treatment of hepatocellular carcinoma.

OBJECTIVE: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE) with embospheres for the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: Patients with unresectable HCC who were treated with TACE followed by embosphere treatment (Embo-TACE) or conventional TACE (cTACE) between May 2010 and March 2014 were retrospectively included in this study. The Embo-TACE group received lipiodol and chemotherapeutic agent emulsion, followed by embospheres. The cTACE group received lipiodol and chemotherapeutic agent emulsion, followed by gelatin sponge pellets. Time to progression (TTP), overall survival (OS), overall response rate (ORR), and safety were compared between the two groups. Univariate and multivariate regression analyses of the factors affecting survival were conducted. RESULTS: The median TTP and OS in the Embo-TACE group were significantly longer than those in the cTACE group (TPP: 7.0 months vs 5.4 months, P = 0.035; OS: 15 months vs 12 months, P = 0.032). Seven days after the first TACE treatment, alanine aminotransferase level was higher in the cTACE group than in the Embo-TACE group (P = 0.015). The ORR did not significantly differ between the two groups (P = 0.827). Additional therapy and local responses one month after the first TACE treatment were associated with OS. CONCLUSIONS: Embo-TACE resulted in a significant improvement in TTP and OS for patients with unresectable HCC, compared with cTACE. Furthermore, Embo-TACE was better tolerated. Additional therapy and local responses one month after the first TACE were independent prognostic factors for OS.