Identification of disulfidptosis-related genes with immune infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant primary tumor that is usually diagnosed at an advanced stage; thus, there is an urgent need for efficient and sensitive novel diagnostic markers to determine the prognosis and halt disease progression in patients with HCC. Disulfidptosis is a recently discovered form of programmed cell death, essentially an abnormal accumulation of intracellular bisulfides. Therefore, our study aimed to investigate the role of disulfidptosis-related genes (DRGs) in the pathogenesis of HCC. Based on public databases, our work demonstrates the relationship between DRG and expression, immunity, mutation/drug sensitivity, and functional enrichment in HCC. We also revealed the significant heterogeneity of HCC in different DRGs sub-clusters and in differentially expressed genes (DEGs), respectively. Subsequently, the most relevant candidate gene, SLC7A11, was screened by machine learning to further validate the significance of SLC7A11 in the clinical features, prognosis, nomogram pattern, and immune infiltration of HCC. Our study, which elucidates the potential mechanisms of DRGs and HCC, reveals that SLC7A11 can serve as a novel prognostic biomarker and provides opportunities and challenges for individualized cancer immunotherapy strategies.

[Health Benefit Evaluation for PM2.5 as Well as O3-8h Pollution Control in Chengdu, China from 2016 to 2020].

Both particulate matter with aerodynamics of less than 2.5 (PM2.5) and ozone are the two main air pollutants in China, which seriously endanger human health. To estimate the adverse impacts of PM2.5 and ozone on human health during the implementation of air pollution prevention and control actions in Chengdu, both the generalized additive model and the nonlinear distribution lag model of epidemiology were adopted to explore the exposure-response relationship coefficients ß of daily ozone 8h maximum concentration average (O3-8h), as well as that of PM2.5 on disease deaths in Chengdu from 2014 to 2016. On this basis, the environmental risk model and environmental value assessment model were both adopted to evaluate the health effects and health benefits in Chengdu from 2016 to 2020, respectively, with the assumption that PM2.5 and O3-8h concentration were reduced to specified air pollution control limits (35 µg·m-3 and 70 µg·m-3, respectively). The results showed 1 the annual concentration of PM2.5 presented gradually decreasing trends in Chengdu from 2016 to 2020. Specifically, ρ(PM2.5) from 63 µg·m-3 in 2016 decreased to 40.92 µg·m-3 in 2020. The average annual decline rate was approximately 9.8%. In contrast, the annual concentration of O3-8h from 155 µg·m-3 in 2016 increased to 169 µg·m-3 in 2020, and the increasing rate was approximately 2.4%. 2 Both PM2.5 and O3-8h had lag effects on three types of disease deaths. Under the maximum lag effect, the corresponding exposure-response relationship coefficients ß of PM2.5were 0.0003600, 0.0005001, and 0.0009237 for all-cause, cardiovascular, and respiratory premature deaths, respectively, whereas the corresponding ß of O3-8h were 0.0003103, 0.0006726, and 0.0007002, respectively. 3 If ρ(PM2.5) was reduced to the national secondary standard limit (35 µg·m-3), the corresponding number of health beneficiaries and economic benefits declined yearly. Specifically, the health beneficiary number of all-cause, cardiovascular, and respiratory disease deaths were reduced from 1128, 416, and 328 in 2016 to 229, 96, and 54 in 2020, respectively. There were a total number of 3314 avoidable premature deaths for all-cause diseases during the five years, resulting in a total health economic benefit of 7.66 billion yuan. 4 If we assume that ρ(O3-8h) was reduced to the concentration limit specified by the World Health Organization (70 µg·m-3), the corresponding number of health beneficiaries and economic benefits were increasing yearly. Specifically, the health beneficiaries' numbers of all-cause, cardiovascular, and respiratory disease deaths rose from 1919, 779, and 606 in 2016 to 2429, 1157, and 635 in 2020, respectively. The annual average growth rates of avoidable all-cause and cardiovascular mortality were 6.85% and 10.72%, respectively, which was higher than the annual average rise rate of ρ(O3-8h). There were 10790 total avoidable deaths from all-cause diseases during the five years, resulting in a total health economic benefit of 26.62 billion yuan. These findings indicate that PM2.5 pollution in Chengdu had been well controlled, whereas O3 pollution had become more severe and had become another key air pollutant threatening human health. Therefore, the synchronous control of PM2.5 and ozone should be implemented in the future.

Darinaparsin (ZIO-101) enhances the sensitivity of small-cell lung cancer to PARP inhibitors.

Small-cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma of the lung associated with early metastasis and an exceptionally poor prognosis. Little progress has been made in developing efficacious targeted therapy for this recalcitrant disease. Herein, we showed that H3.3, encoded by two genes (H3F3A and H3F3B), was prominently overexpressed in SCLC. Darinaparsin (ZIO-101), a derivative of arsenic trioxide, dose- and time-dependently inhibited the viability of SCLC cells in an H3.3-dependent manner. More importantly, ZIO-101 treatment resulted in substantial accumulation of H3.3 and PARP1 besides induction of G2/M cell cycle arrest and apoptosis in SCLC cells. Through integrative analysis of the RNA-seq data from Cancer Cell Line Encyclopedia dataset, JNCI and Genomics of Drug Sensitivity in Cancer 2 datasets, we found that H3F3A expression was negatively correlated with the IC50 values of PARP inhibitors (PARPi). Furthermore, co-targeting H3.3 and PARP1 by ZIO-101 and BMN673/olaparib achieved synergistic growth inhibition against SCLC in vitro and in vivo. In conclusion, it is feasible to target H3.3 by ZIO-101 to potentiate the response rate of PARPi in SCLC patients.

LAMP2 as a Biomarker Related to Prognosis and Immune Infiltration in Esophageal Cancer and Other Cancers: A Comprehensive Pan-Cancer Analysis.

Esophageal cancer (ESCA) is a common malignant tumor with poor prognosis. Accumulating evidence indicates an important role of lysosomal-associated membrane protein 2 (LAMP2) in the progression and development of various cancers. In this study, we obtained RNA-sequencing raw count data and the corresponding clinical information for ESCA samples from The Cancer Genome Atlas and Gene Expression Omnibus databases. We comprehensively investigated the expression and prognostic significance of LAMP2 and relationships between LAMP2 expression and prognosis, different clinicopathological parameters, and immune cell infiltration in ESCA. We also obtained the differentially expressed genes between the high LAMP2 expression and low LAMP2 expression groups in ESCA and performed a functional enrichment analysis of the 250 linked genes most positively related to LAMP2 expression. Moreover, we performed the pan-cancer analysis of LAMP2 to further analyze the role of LAMP2 in 25 commonly occurring types of human cancer. We also verified and compared the expression of LAMP2 in 40 samples of human ESCA tissue and adjacent tissues. The results indicated that LAMP2 expression was significantly upregulated in ESCA and various human cancers. In addition, LAMP2 expression was associated with certain clinicopathological parameters, prognosis, and immune infiltration in ESCA and the other types of cancer. Our study represents a comprehensive pan-cancer analysis of LAMP2 and supports the potential use of the modulation of LAMP2 in the management of ESCA and various cancers.

MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma.

The long-term prognosis of patients with lung cancer remains poor and thus it is imminent to further elucidate the molecular mechanism for the oncogenesis of lung cancer. In this study, we observed that surfactant protein C (SFTPC) expression was downregulated in human lung adenocarcinoma tissues and cell lines, and low SFTPC expression correlated with poor overall survival of lung adenocarcinoma patients. Moreover, we found that overexpression of SFTPC could inhibit lung cancer cell proliferation in vitro and in vivo, but downregulation of SFTPC showed the opposite results. Besides, it was observed that miR-629-3p expression was upregulated in human lung adenocarcinoma tissues and cell lines. More importantly, we found that miR-629-3p could downregulate SFTPC expression by directly binding to the SFTPC 3'-UTR and inhibit the regulatory effect of SFTPC on lung adenocarcinoma cell proliferation. In conclusion, these data suggested that miR-629-3p-meditated downregulation of SFTPC may promote lung adenocarcinoma progression.

Metastatic retinoblastoma of the parotid and submandibular glands: a rare case report.

BACKGROUND: Retinoblastoma is the most common intraocular malignancy occurring in children. It can metastasize to the regional lymph nodes, central nervous system and distant organs usually the bones and bone marrow and very rarely to the soft tissue. Here, we report a case of unilateral retinoblastoma in a 4-year-old girl accompanied by a large metastasis of the parotid and submandibular glands that developed about 6 months previously and gradually increased in size 5 months after enucleation of the left eye. CASE PRESENTATION: A 4-year-old girl with a history of unilateral retinoblastoma presented with a large, painful and worsening mass (about 20 × 23 cm) of the left side of the neck. Following surgery, the orbital tumour was completely resected, and the large tumour invasion range in the left side of the neck was not resected completely. Histopathological examination revealed retinoblastoma of the orbit and the parotid and submandibular glands. After chemotherapy and additional local radiotherapy on the parotid and submandibular glands, the tumour was inactive and stable. CONCLUSIONS: Delayed detection and inappropriate management contribute to poor outcomes. Fundus examinations, education regarding the early signs of RB, and optimization of the therapeutic strategy for RB may play important roles in ocular health.

Clinical efficacy and safety of limited internal fixation combined with external fixation for Pilon fracture: A systematic review and meta-analysis.

PURPOSE: To compare the clinical efficacy and complications of limited internal fixation combined with external fixation (LIFEF) and open reduction and internal fixation (ORIF) in the treatment of Pilon fracture. METHODS: We searched databases including Pubmed, Embase, Web of science, Cochrane Library and China Biology Medicine disc for the studies comparing clinical efficacy and complications of LIFEF and ORIF in the treatment of Pilon fracture. The clinical efficacy was evaluated by the rate of nonunion, malunion/delayed union and the excellent/good rate assessed by Mazur ankle score. The complications including infections and arthritis symptoms after surgery were also investigated. RESULTS: Nine trials including 498 pilon fractures of 494 patients were identified. The meta-analysis found no significant differences in nonunion rate (RR = 1.60, 95% CI: 0.66 to 3.86, p = 0.30), and the excellent/good rate (RR = 0.95, 95% CI: 0.86 to 1.04, p = 0.28) between LIFEF group and ORIF group. For assessment of infections, there were significant differences in the rate of deep infection (RR = 2.18, 95% CI: 1.34 to 3.55, p = 0.002), and the rate of arthritis (RR = 1.26, 95% CI: 1.03 to 1.53, p = 0.02) between LIFEF group and ORIF group. CONCLUSION: LIFEF has similar effect as ORIF in the treatment of pilon fractures, however, LIFEF group has significantly higher risk of complications than ORIF group does. So LIFEF is not recommended in the treatment of pilon fracture.

Effects of lentiviral RNA interference-mediated downregulation of integrin-linked kinase on biological behaviors of human lens epithelial cells.

AIM: To investigate the effects of lentivirus (LV) mediated integrin-linked kinase (ILK) RNA interference (RNAi) on biological behaviors of human lens epithelial cells (LECs). METHODS: Human cataract LECs and immortalized human LEC line, human lens epithelial (HLE) B-3 cells were transfected by lentiviral vector expressing ILK-specific short hairpin RNA (shRNA) and then stimulated by transforming growth factor-ß (TGF-ß), the silencing of ILK gene and protein was identified by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot methods; biological behaviors including cell cycle and apoptosis, cell morphology, α-smooth muscle actin (SMA) stress fiber formation and cell migration were examined. RESULTS: Remarkable decreases of ILK protein expression were detected in LECs carrying lentiviral ILK-shRNA vector; flow cytometry revealed arresting of cell cycle progression through the G1/S transition and higher apoptosis rate in ILK-RNAi-LV transfected cells. Less α-SMA stress fiber formation and migration was observed in ILK-RNAi-LV transfected LECs. CONCLUSION: The present study demonstrated that ILK was an important regulator for LECs proliferation and migration. LV mediated ILK RNAi is an effective way to decrease ILK-regulated cell growth by arresting cell cycle progression and increasing cell apoptosis, as well as, to prevent cell migration by inhibiting TGF-ß induced α-SMA stress fiber formation. Thus, LV mediated ILK RNAi might be useful to prevent posterior capsular opacification.

Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol.

AIMS: The intravenous anesthetic propofol caused episodic memory impairments in human. We hypothesized propofol caused episodic-like spatial memory retention but not acquisition impairments in rats and rescuing cAMP response element-binding protein (CREB) signaling using selective type IV phosphodiesterase (PDEIV) inhibitor rolipram reversed these effects. METHODS: Male Sprague-Dawley rats were randomized into four groups: control; propofol (25 mg/kg, intraperitoneal); rolipram; and rolipram + propofol (pretreatment of rolipram 25 min before propofol, 0.3 mg/kg, intraperitoneal). Sedation and motor coordination were evaluated 5, 15, and 25 min after propofol injection. Invisible Morris water maze (MWM) acquisition and probe test (memory retention) were performed 5 min and 24 h after propofol injection. Visible MWM training was simultaneously performed to resist nonspatial effects. Hippocampal CREB signaling was detected 5 min, 50 min, and 24 h after propofol administration. RESULTS: Rolipram did not change propofol-induced anesthetic/sedative states or impair motor skills. No difference was found on the latency to the platform during the visible MWM. Propofol impaired spatial memory retention but not acquisition. Rolipram reversed propofol-induced spatial memory impairments and suppression on cAMP levels, CaMKIIα and CREB phosphorylation, brain-derived neurotropic factor (BDNF) and Arc protein expression. CONCLUSIONS: Propofol caused spatial memory retention impairments but not acquisition inability possibly by inhibiting CREB signaling.

Graphene oxide hydrogel at solid/liquid interface.

A strong solid/liquid interfacial interaction is found between porous alumina and graphene oxide (GO) aqueous dispersion, which promotes a fast enrichment of GO on the alumina surface and results in the formation of a GO hydrogel.

[Effect of intra-abdominal pressure on respiratory system, circulatory system and renal function in rats and study on the method of determination of intra-abdominal pressure].

UNLABELLED: OBJECTIVE To study the effects of intra-abdominal pressure (IAP) on respiratory system, circulatory system and renal function in rats. To investigate the difference between the direct measure and indirect measure methods (via inferior vena cava and bladder) for IAP. METHODS: Sixty Sprague-Drawly (SD) rats were randomly divided into 5 groups with different IAP (IAP value of 1-5 groups was 5, 10, 15, 20, 25 mm Hg,respectively) and healthy control group, 10 rats in each group. The parameters of respiratory system, circulatory system, renal function, and IAP value were recorded. The correlation between direct and indirect measurement methods was also analyzed. RESULTS: There were no significant differences in above parameters between IAPI and healthy control groups. Compared with those in healthy control group, PaO2 significantly decreased (P < 0.05), SCr and BUN increased significantly in IAP2 group (P < 0.05). Other indexes in IAP3, IAP4 groups increased (P < 0.05 or P < 0.01) except for respiratory frequency(RF) and MAP (P > 0.05). PaO2 and MAP decreased (P < 0.01), and other indexes increased (P < 0.05 or P < 0.01) in IAP5 group. The values obtained from the indirect measure method were positively correlated with that from the direct measure method (r = 0.937, 0.955, P < 0.01, respectively). CONCLUSIONS: IAP can affect respiratory system, circulatory system and renal function in different degrees in rats. The indirect measure method can replace the direct measure method for IAP measure with little injuries.

Study of the electrochemical behavior of isorhamnetin on a glassy carbon electrode and its application.

The electrochemical behavior of isorhamnetin (ISO) at a glassy carbon electrode was studied in a phosphate buffer solution (PBS) of pH 4.0 by cyclic voltammetry (CV) and differential pulse voltammetric method (DPV). A well-defined redox wave of ISO involving one electrons and one proton appeared. The electrode reaction is a reactant weak adsorption-controlled process with a charge transfer coefficient (alpha) of 0.586. Based on the understanding of the electrochemical process of ISO at the glassy carbon electrode, analysis of ISO can be realized. Under optimal conditions, the oxidation peak current showed linear dependence on the concentration of ISO in the range of 1.0x10(-8) to 4.0x10(-7)M and 1.0x10(-6) to 1.0x10(-5)M. The detection limit is 5.0x10(-9)M. This method has been successfully applied to the detection of ISO in tablets.

Simultaneous voltammetric determination of norepinephrine, ascorbic acid and uric acid on polycalconcarboxylic acid modified glassy carbon electrode.

A novel polycalconcarboxylic acid (CCA) modified glassy carbon electrode (GCE) was fabricated by electropolymerization and then successfully used to simultaneously determine ascorbic acid (AA), norepinephrine (NE) and uric acid (UA). The characterization of electrochemically synthesized Poly-CCA film was investigated by atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS) and voltammetric methods. It was found that the electrochemical behavior of the polymer-modified electrode depended on film thickness, i.e., the electropylmyerization time. Based on the electrochemical data, the charge transfer coefficient (alpha) and the surface coverage (Gamma) were calculated. This poly-CCA modified GCE could reduce the overpotential of ascorbic acid (AA), norepinephrine (NE) and uric acid (UA) oxidation in phosphate buffer solution (pH 6.0), while it increases the peak current significantly. The current peak separations of AA/NE, NE/UA and AA/UA on this modified electrode are 91mV, 256mV and 390mV in CV at 100mVs(-1), respectively. Therefore, the voltammetric responses of these three compounds can be well resolved on the polymer-modified electrode, and simultaneously determination of these three compounds can be achieved. In addition, this modified electrode can be successfully applied to determine AA and NE in injection and UA in urine samples without interferences.