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Background: To examine the trends in morbidity and mortality among ovarian cancer patients with liver metastases, and investigate the impact of different treatments on both overall survival (OS) and cancer-specific survival (CSS). Methods: 2,925 ovarian cancer patients with liver metastases from Surveillance, Epidemiology, and End Results 2010–2019 were included. The primary endpoint was considered as OS and CSS. We conducted trend analysis of the incidence, OS and CSS rates of liver metastases in ovarian cancer. Univariate and multivariate COX proportional risk models were used to investigate the association between different treatment methods and OS, and univariate and multivariate competing risk models were employed to evaluate the impact of treatment methods on CSS. Results: At the end of follow-up, 689 patients remained alive. The OS and CSS rates were 76.44% and 72.99% for all patients, respectively. There was a significant decreasing trend in the incidence [average annual percent change (AAPC) = -2.3, 95% confidence interval (CI): -3.9, -0.7], all-cause mortality (AAPC = -12.8, 95% CI: -15.6, -9.9) and specific mortality (AAPC = -13.0, 95% CI: -16.1, -9.8) rate of liver metastases in ovarian cancer. After adjusting all confounding factor, only receiving surgery was associated with OS [hazard ratio (HR) = 0.39, 95%CI: 0.31–0.48]/CSS (HR = 0.37, 95%CI: 0.30–0.47). Chemotherapy was found to be protective factor for OS (HR = 0.33, 95%CI: 0.30–0.37)/CSS (HR = 0.44, 95%CI: 0.39–0.50) of ovarian cancer patients, while not receiving surgery remained a risk factor. Additionally, the result of subgroup analyses also showed that only receiving surgery and chemotherapy still were significant protective factor of OS and CSS for patients without other distant metastases, with distant metastases to the bone, lung, brain or other organs, with bone metastasis, and with lung metastasis. Conclusion: Our research has elucidated a downward trend in morbidity and mortality rates among patients with liver metastases originating from ovarian cancer. Only receiving surgery and chemotherapy as therapies methods confer survival benefits to patients. [ABSTRACT FROM AUTHOR]

The school students are facing mental health issues, and their performance is not improving in China. Health education policies are not implemented at the school level in China. However, scholars focus on college students' health education, but the school student is neglected. The research's primary objective is to answer the question: What is the impact of health education on the psychological well-being of school students? A sample of 549 10th grade students is collected from China's public and private sector institutes. The partial least square–structural equation modelling (PLS-SEM) is employed to analyze the data. The outcomes highlighted that the impact of health education is significant on the psychological well-being of school students in China. Furthermore, the study introduced that the moderating role of sustainable health exercise and sports participation is critical as it positively influences the relationship between health education and psychological wellbeing. This research improves literature as the novel contribution are highlighted in theory. Furthermore, the government education policies must be reframed under the light of this research' findings to improve students' health. [ABSTRACT FROM AUTHOR]

The Nrf2/Keap1 axis plays a complex role in viral susceptibility, virus-associated inflammation and immune regulation in host cells. However, whether or how the Nrf2/Keap1 axis is involved in the interactions between equine lentiviruses and their hosts remains unclear. Here, we demonstrate that the Nrf2/Keap1 axis was activated during EIAV infection. Mechanistically, EIAV-Rev competitively binds to Keap1 and releases Nrf2 from Keap1-mediated repression, leading to the accumulation of Nrf2 in the nucleus and promoting Nrf2 responsive genes transcription. Subsequently, we demonstrated that the Nrf2/Keap1 axis represses EIAV replication via two independent molecular mechanisms: directly increasing antioxidant enzymes to promote effective cellular resistance against EIAV infection, and repression of Rev-mediated RNA transport through direct interaction between Keap1 and Rev. Together, these data suggest that activation of the Nrf2/Keap1 axis mediates a passive defensive response to combat EIAV infection. The Nrf2/Keap1 axis could be a potential target for developing strategies for combating EIAV infection. Author summary: Here we report that the Nrf2/Keap1 axis acts as an antiviral effector on EIAV replication through two-way regulation of Rev. On the one hand, EIAV-Rev activates the Nrf2/Keap1 axis through a competitive interaction with Keap1, and promotes the transcription of cytoprotective genes implicated in the antiviral response. On the other hand, Keap1 restricts Rev/RRE-dependent RNA transport, leading to inhibition of viral protein synthesis and a reduction in viral replication. This study highlights the importance of the Nrf2/Keap1 axis in controlling EIAV replication, and identifies this pathway as a potential new entry-point for treating lentivirus infection. Importantly, this report provides new insights into the regulation of viral replication by the Nrf2/Keap1 axis. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive surgery (MIS) provides a new approach for patients with hilar cholangiocarcinoma (HCCA). However, whether it can achieve similar outcomes to traditional open surgery (OS) remains controversial. Methods: To assess the safety and feasibility of MIS for HCCA, a systematic review and meta-analysis was performed to compare the outcomes of MIS with OS. Seventeen outcomes were assessed. Results: Nine studies involving 382 patients were included. MIS was comparable in blood transfusion rate, R0 resection rate, lymph nodes received, overall morbidity, severe morbidity (Clavien–Dindo classification > = 3), bile leakage rate, wound infection rate, intra-abdominal infection rate, days until oral feeding, 1-year overall survival, 2-year overall survival and postoperative mortality with OS. Although operation time was longer (mean difference (MD) = 93.51, 95% confidence interval (CI) = 64.10 to 122.91, P < 0.00001) and hospital cost (MD = 0.68, 95% CI = 0.03 to 1.33, P = 0.04) was higher in MIS, MIS was associated with advantages of minimal invasiveness, that was less blood loss (MD = -81.85, 95% CI = -92.09 to -71.62, P < 0.00001), less postoperative pain (MD = -1.21, 95% CI = -1.63 to -0.79, P < 0.00001), and shorter hospital stay (MD = -4.22, 95% CI = -5.65 to -2.80, P < 0.00001). Conclusions: The safety and feasibility of MIS for HCCA is acceptable in selected patients. MIS is a remarkable alternative to OS for providing comparable outcomes associated with a benefit of minimal invasiveness and its application should be considered more. [ABSTRACT FROM AUTHOR]

Objective: To investigate the biomechanical effects of the lumbar posterior complex on the adjacent segments after posterior lumbar interbody fusion (PLIF) surgeries. Methods: A finite element model of the L1–S1 segment was modified to simulate PLIF with total laminectomy (PLIF-LAM) and PLIF with hemilaminectomy (PLIF-HEMI) procedures. The models were subjected to a 400N follower load with a 7.5-N.m moment of flexion, extension, torsion, and lateral bending. The range of motion (ROM), intradiscal pressure (IDP), and ligament force were compared. Results: In Flexion, the ROM, IDP and ligament force of posterior longitudinal ligament, intertransverse ligament, and capsular ligament remarkably increased at the proximal adjacent segment in the PLIF-LAM model, and slightly increased in the PLIF-HEMI model. There was almost no difference for the ROM, IDP and ligament force at L5-S1 level between the two PLIF models although the ligament forces of ligamenta flava remarkably increased compared with the intact lumbar spine (INT) model. For the other loading conditions, these two models almost showed no difference in ROM, IDP and ligament force on the adjacent discs. Conclusions: Preserved posterior complex acts as the posterior tension band during PLIF surgery and results in less ROM, IDP and ligament forces on the proximal adjacent segment in flexion. Preserving the posterior complex during decompression can be effective on preventing adjacent segment degeneration (ASD) following PLIF surgeries. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and toxicities in T4 nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT) combined with chemotherapy. Methods: This is a retrospective analysis of 81 patients treated with intensity-modulated radiotherapy (IMRT). All the primary tumors were attributed to T4 stage according to the AJCC2010 staging system. And the distribution of disease by N stage was N0 in 13.6%, N1 in 30.9%, N2 in 37%, and N3 in 18.5%. Cisplatin-based chemotherapy was offered to all patients. Radiotherapy-related toxicities were graded according to the Acute and the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group (RTOG) scoring criteria. Chemotherapy-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Prognostic factors were assessed by univariate analysis. Results: With a median follow-up of 37 months, 12 patients experienced local regional failure and total distant metastasis occurred in 18 patients, representing the major mode of failure. Ten patients died. Among them, 70% died of distant metastasis. The 3-year actuarial rates of local failure–free survival (LFFS), regional failure–free survival (RFFS), distant failure–free survival (DFFS), overall survival (OS), and progression–free survival (PFS) were 83.8%, 97.4%, 81.3%, 90%, and 69.7%, respectively. Acute and late toxicities were mild or moderate. Conclusions: IMRT provides excellent local-regional control for T4 NPC. Distant metastasis remains the major cause of treatment failure. Further explorations of the sequence and regimen of systemic therapy are needed in the future. [ABSTRACT FROM AUTHOR]

DNA damage to cochlear hair cells caused by 8-oxoguanine (8-oxoG) is essential for the development of noise-induced hearing loss (NIHL). Human 8-oxoG DNA glycosylase1 (hOGG1) is a key enzyme in the base excision repair (BER) pathway that eliminates 8-oxoG. Many epidemiological and functional studies have suggested that the hOGG1 Ser326Cys polymorphism (rs1052133) is associated with many diseases. The purpose of this investigation was to investigate whether the hOGG1 Ser326Cys polymorphism in the human BER pathway is associated with genetic susceptibility to NIHL in a Chinese population. This polymorphism was genotyped among 612 workers with NIHL and 615 workers with normal hearing. We found that individuals with the hOGG1 Cys/Cys genotype had a statistically significantly increased risk of NIHL compared with those who carried the hOGG1 Ser/Ser genotype (adjusted OR = 1.59, 95% CI = 1.13–2.25) and this increased risk was more pronounced among the workers in the 15- to 25- and >25-year noise exposure time, 85–92 dB(A) noise exposure level, ever smoking, and ever drinking groups, similar effects were also observed in a recessive model. In summary, our data suggested that the hOGG1 Cys/Cys genotype may be a genetic susceptibility marker for NIHL in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for equine infectious anemia virus (EIAV) and is a member of the tumor necrosis factor receptor (TNFR) superfamily. In addition to the previously described membrane-associated form of ELR1, two other major alternative splicing variant mRNAs were identified in equine monocyte-derived macrophages (eMDMs). One major spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a premature stop codon situated 561 nt upstream of the predicted membrane spanning domain. The other major species (ELR1-DE) has a deletion of 109 nt that causes a shift of the open reading frame and generates a stop codon 312 nt downstream. Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN was further analyzed. The expression of a soluble form of ELR1 (sELR1) by ELR1-IN was confirmed by Western blot and immunofluorescence analyses. Similar to ELR1, the transcription level of ELR1-IN varied among individual horses and at different time points in the same individuals. The ratio of ELR1-IN mRNA species to ELR1 mRNA was approximately 1∶2.5. Pre-incubation of the recombinant sELR1 with EIAV significantly inhibited EIAV infection in equine macrophages, the primary in vivo target cell of the virus. Fetal equine dermal (FED) cells are susceptible to EIAV in vitro, and the replication of EIAV in FED cells transiently transfected with ELR1-IN was markedly reduced when compared with replication in cells transfected with the empty vector. Finally, the expression levels of both forms of the EIAV receptor were significantly regulated by infection with this virus. Taken together, our data indicate that sELR1 acts as a secreted cellular factor that inhibits EIAV infection in host cells. [ABSTRACT FROM AUTHOR]

DNA damage to cochlear hair cells caused by 8-oxoguanine (8-oxoG) is essential for the development of noise-induced hearing loss (NIHL). Human 8-oxoG DNA glycosylase1 (hOGG1) is a key enzyme in the base excision repair (BER) pathway that eliminates 8-oxoG. Many epidemiological and functional studies have suggested that the hOGG1 Ser326Cys polymorphism (rs1052133) is associated with many diseases. The purpose of this investigation was to investigate whether the hOGG1 Ser326Cys polymorphism in the human BER pathway is associated with genetic susceptibility to NIHL in a Chinese population. This polymorphism was genotyped among 612 workers with NIHL and 615 workers with normal hearing. We found that individuals with the hOGG1 Cys/Cys genotype had a statistically significantly increased risk of NIHL compared with those who carried the hOGG1 Ser/Ser genotype (adjusted OR=1.59, 95% CI=1.13-2.25) and this increased risk was more pronounced among the workers in the 15- to 25- and >25-year noise exposure time, 85-92 dB(A) noise exposure level, ever smoking, and ever drinking groups, similar effects were also observed in a recessive model. In summary, our data suggested that the hOGG1 Cys/Cys genotype may be a genetic susceptibility marker for NIHL in the Chinese Han population.

The stability and subcellular localization of beta-catenin, a protein that plays a major role in cell adhesion and proliferation, is tightly regulated by multiple signaling pathways. While aberrant activation of beta-catenin signaling has been implicated in cancers, the biochemical identity of transcriptionally active beta-catenin (ABC), commonly known as unphosphorylated serine 37 (S37) and threonine 41 (T41) β-catenin, remains elusive. Our current study demonstrates that ABC transcriptional activity is influenced by phosphorylation of T120 by Protein Kinase D1 (PKD1). Whereas the nuclear β-catenin from PKD1-low prostate cancer cell line C4-2 is unphosphorylated S37/T41/T120 with high transcription activity, the nuclear β-catenin from PKD1-overexpressing C4-2 cells is highly phosphorylated at T120, S37 and T41 with low transcription activity, implying that accumulation of nuclear β-catenin alone cannot be simply used as a read-out for Wnt activation. In human normal prostate tissue, the phosphorylated T120 β-catenin is mainly localized to the trans-Golgi network (TGN, 22/30, 73%), and this pattern is significantly altered in prostate cancer (14/197, 7.1%), which is consistent with known down regulation of PKD1 in prostate cancer. These in vitro and in vivo data unveil a previously unrecognized post-translational modification of ABC through T120 phosphorylation by PKD1, which alters subcellular localization and transcriptional activity of β-catenin. Our results support the view that β-catenin signaling activity is regulated by spatial compartmentation and post-translational modifications and protein level of β-catenin alone is insufficient to count signaling activity.

Background: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+)-activated potassium (BK(Ca)) channel in zoledronic acid-induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer cells., Methodology/principal Findings: The action of zoledronic acid on BK(Ca) channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293) cells which were transfected with functional BK(Ca) α-subunit (hSloα). Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca) channels, and then activation of BK(Ca) channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+) and a concomitant depolarization of mitochondrial membrane potential (Δψm) in MDA-MB-231 cells., Conclusions: Activation of BK(Ca) channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro.