Identification of functional genes regulating gastric cancer progression using integrated bioinformatics analysis.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers and has a poor prognosis. Treatment of GC has remained unchanged over the past few years. AIM: To investigate the potential therapeutic targets and related regulatory biomarkers of GC. METHODS: We obtained the public GC transcriptome sequencing dataset from the Gene Expression Omnibus database. The datasets contained 348 GC tissues and 141 healthy tissues. In total, 251 differentially expressed genes (DEGs) were identified, including 187 down-regulated genes and 64 up-regulated genes. The DEGs' enriched functions and pathways include Progesterone-mediated oocyte maturation, cell cycle, and oocyte meiosis, Hepatitis B, and the Hippo signaling pathway. Survival analysis showed that BUB1, MAD2L1, CCNA2, CCNB1, and BIRC5 may be associated with regulation of the cell cycle phase mitotic spindle checkpoint pathway. We selected 26 regulated genes with the aid of the protein-protein interaction network analyzed by Molecular Complex Detection. RESULTS: We focused on three critical genes, which were highly expressed in GC, but negatively related to patient survival. Furthermore, we found that knockdown of BIRC5, TRIP13 or UBE2C significantly inhibited cell proliferation and induced cell apoptosis. In addition, knockdown of BIRC5, TRIP13 or UBE2C increased cellular sensitivity to cisplatin. CONCLUSION: Our study identified significantly upregulated genes in GC with a poor prognosis using integrated bioinformatics methods.

Heart Rate Response Predicts 6-Minutes Walking Distance in Pulmonary Arterial Hypertension.

Because the 6-minute walking test (6MWT) is a self-paced submaximal test, the 6-minute walking distance (6MWD) is substantially influenced by individual effort level and physical condition, which is difficult to quantify. We aimed to explore the optimal indicator reflecting the perceived effort level during 6MWT. We prospectively enrolled 76 patients with pulmonary arterial hypertension and 152 healthy participants; they performed 2 6MWTs at 2 different speeds: (1) at leisurely speed, as performed in daily life without extra effort (leisure 6MWT) and (2) an increased walking speed, walking as the guideline indicated (standard 6MWT). The factors associated with 6MWD during standard 6MWT were investigated using a multiple linear regression analysis. The heart rate (HR) and Borg score increased and oxygen saturation (SpO2) decreased after walking in 2 6MWTs in both groups (all p <0.001). The ratio of difference in HR before and after each test (ΔHR) to HR before walking (HRat rest) and the difference in SpO2 (ΔSpO2) and Borg (ΔBorg) before and after each test were all significantly higher in both groups after standard 6MWT than after leisure 6MWT (all p <0.001). Multiple linear regression analysis revealed that ΔHR/HRat rest was an independent predictor of 6MWD during standard 6MWT in both groups (both p <0.001, adjusted R2 = 0.737 and 0.49, respectively). 6MWD and ΔHR/HRat rest were significantly lower in patients than in healthy participants (both p <0.001) and in patients with cardiac functional class III than in patients with class I/II (both p <0.001). In conclusion, ΔHR/HRat rest is a good reflector of combined physical and effort factors. HR response should be incorporated into 6MWD to better assess a participant's exercise capacity.

Percutaneous transluminal pulmonary angioplasty for Takayasu arteritis-associated pulmonary hypertension: A single-arm meta-analysis.

BACKGROUND: The efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear. OBJECTIVES: To examine the efficacy and safety of PTPA in TA-PH. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials Library were searched from inception to August 18, 2022, for articles investigating the efficacy and safety of PTPA for TA-PH. The primary efficacy outcomes were pulmonary vascular resistance (PVR) changes from baseline to re-evaluation and 6-minute walking distance (6MWD). The safety outcome was procedure-related complications. RESULTS: Five articles comprising 104 patients with TA-PH who underwent PTPA were included. The scores of article quality, as assessed using the methodological index for nonrandomized studies tool, were high, ranging from 13 to 15 points. The pooled treatment effects of PVR (weighted mean difference [WMD]: -4.8 WU; 95% confidence interval [CI]: -6.0 to -3.5 WU; I2 = 0.0%), 6MWD (WMD: 101.9 m; 95% CI: 60.3-143.6 m; I2 = 70.4%) significantly improved. Procedure-related complications, which predominantly present as pulmonary artery injury and pulmonary injury, occurred in 32.0% of the included patients. Periprocedural death occurred in one patient (1.0%, 1/100). CONCLUSIONS: Patients with TA-PH could benefit from PTPA in terms of hemodynamics and exercise tolerance, at the expense of procedure-related complications. PTPA should be encouraged to enhance the treatment response in TA-PH. These findings need to be confirmed by further studies, ideally, randomized controlled trials. REGISTRATION: PROSPERO CRD42022354087.

LncRNA AK001796 promotes cell proliferation via acting as a ceRNA of miR-150 in hepatocellular carcinoma.

Long non-coding RNA AK001796 was initially identified altered in lung cancer. Recent research showed it could participate in the prognosis of hepatocellular carcinoma (HCC). However, the general biological role of AK001796 and its underlying mechanisms in HCC remain unclear. Here we demonstrated that the expression level of AK001796 in HCC tissues and cell lines was up-regulated. Silencing AK001796 suppressed the proliferation ability of HCC cells. Through dual luciferase reporter assays and loss/gain of functions studies, we identified that AK001796 could bind to miR-150, a star microRNA, promoting HCC proliferation. Furthermore, it was reported that growth factor receptor binding protein 2-associated binder 1 (GAB1) is a target gene of miR-150. Owing to AK001796 being a decoy for miR-150 and binding the same putative sites of miR-150 as GAB1, we presented that inhibition of miR-150 in AK001796 silencing cells reversed the reduction in GAB1. Subsequently, our findings demonstrated that silencing AK001796 can impair phospho-ERK1/2 and phospho-AKT. In conclusion, our investigation revealed that AK001796 promoted proliferation by enhancing phospho-ERK1/2 and phospho-AKT through AK001796/miR-150/GAB1 axis in HCC. These results provided further evidence for the critical roles of AK001796 accumulating HCC and suggested that AK001796 might act as an HCC biomarker in clinical treatment.

Constrained Planar Array Thinning Based on Discrete Particle Swarm Optimization with Hybrid Search Strategies.

This article presents a novel optimization algorithm for large array thinning. The algorithm is based on Discrete Particle Swarm Optimization (DPSO) integrated with some different search strategies. It utilizes a global learning strategy to improve the diversity of populations at the early stage of optimization. A dispersive solution set and the gravitational search algorithm are used during particle velocity updating. Then, a local search strategy is enabled in the later stage of optimization. The particle position is adaptively adjusted by the mutation probability, and its motion state is monitored by two observation parameters. The peak side-lobe level (PSLL) performance, effectiveness and robustness of the improved PSO algorithm are verified by several representative examples.

Long non-coding RNA SNHG1 activates glycolysis to promote hepatocellular cancer progression through the miR-326/PKM2 axis.

BACKGROUND: Hepatocellular cancer (HCC) is a lethal malignancy with extremely poor prognosis. In the present study, we aimed to investigate the role and underlying mechanism of SNHG1 in HCC progression. METHODS: Combined with bioinformatics and experimental validation, we explored the clinical significance of SNHG1 in HCC. A Cell Counting Kit-8 assay, cell colony formation assay, and subcutaneous tumorigenesis experiments of nude mice were conducted to evaluate the pro-proliferative capacity of SNHG1. Glucose consumption and lactate production were measured to explore the regulatory role of SNHG1 in glycolysis. Nuclear-cytoplasmic separation, quantitative real-time polymerase chain reaction and Western blot assays, chromatin immunoprecipitation, and luciferase reporter and RNA immunoprecipitation assays were performed to investigate the molecular mechanisms of SNHG1 in HCC. RESULTS: SNHG1 expression was dramatically increased in HCC and positively correlated with poor prognosis. E2F1 bound to the SNHG1 promoter region to activate SNHG1 transcription. Furthermore, SNHG1 served as a molecular sponge for miR-326 to sequester the interaction of miR-326 and pyruvate kinase M2 (PKM2), facilitating the expression of PKM2. Activating PKM2 expression was revealed to be one of mechanisms of SNHG1 with respect to promoting glycolysis and the proliferation of HCC cells. CONCLUSIONS: E2F1-activated SNHG1 modulates the miR-326/PKM2 axis to facilitate glycolysis and the proliferation of HCC cells. Targeting SNHG1 could be a promising therapeutic option for HCC.

DigestPath: A benchmark dataset with challenge review for the pathological detection and segmentation of digestive-system.

Examination of pathological images is the golden standard for diagnosing and screening many kinds of cancers. Multiple datasets, benchmarks, and challenges have been released in recent years, resulting in significant improvements in computer-aided diagnosis (CAD) of related diseases. However, few existing works focus on the digestive system. We released two well-annotated benchmark datasets and organized challenges for the digestive-system pathological cell detection and tissue segmentation, in conjunction with the International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI). This paper first introduces the two released datasets, i.e., signet ring cell detection and colonoscopy tissue segmentation, with the descriptions of data collection, annotation, and potential uses. We also report the set-up, evaluation metrics, and top-performing methods and results of two challenge tasks for cell detection and tissue segmentation. In particular, the challenge received 234 effective submissions from 32 participating teams, where top-performing teams developed advancing approaches and tools for the CAD of digestive pathology. To the best of our knowledge, these are the first released publicly available datasets with corresponding challenges for the digestive-system pathological detection and segmentation. The related datasets and results provide new opportunities for the research and application of digestive pathology.

Percutaneous Pulmonary Angioplasty for Patients With Takayasu Arteritis and Pulmonary Hypertension.

BACKGROUND: Percutaneous transluminal pulmonary angioplasty (PTPA) is a treatment modality for chronic thromboembolic pulmonary hypertension, but whether it can be applied to Takayasu arteritis-associated pulmonary hypertension (TA-PH), another chronic obstructive pulmonary vascular disease, remains unclear. OBJECTIVES: This study sought to investigate the efficacy and safety of PTPA for TA-PH. METHODS: Between January 1, 2016, and December 31, 2019, a total of 50 patients with TA-PH who completed the PTPA procedure (the PTPA group) and 21 patients who refused the PTPA procedure (the non-PTPA group) were prospectively enrolled in this cohort study. The primary outcome was all-cause mortality. The safety outcomes included PTPA procedure-related complications. RESULTS: Baseline characteristics and medical therapies were similar between the PTPA group and the non-PTPA group. During a mean follow-up time of 37 ± 14 months, deaths occurred in 3 patients (6.0%) in the PTPA group and 6 patients (28.6%) in the non-PTPA group, contributing to the 3-year survival rate of 93.7% in the PTPA group and 76.2% in the non-PTPA group (P = 0.0096 for log-rank test). The Cox regression model showed that PTPA was associated with a significantly reduced hazard of all-cause mortality in TA-PH patients (HR: 0.18; 95% CI: 0.05-0.73; P = 0.017). No periprocedural death occurred. Severe complications requiring noninvasive positive pressure ventilation occurred in only 1 of 150 total sessions (0.7%). CONCLUSIONS: PTPA tended to be associated with a reduced risk of all-cause mortality with acceptable safety profiles and seemed to be a promising therapeutic option for TA-PH patients.

A Deep Learning-Based Approach for Glomeruli Instance Segmentation from Multistained Renal Biopsy Pathologic Images.

Glomeruli instance segmentation from pathologic images is a fundamental step in the automatic analysis of renal biopsies. Glomerular histologic manifestations vary widely among diseases and cases, and several special staining methods are necessary for pathologic diagnosis. A robust model is needed to segment and classify glomeruli with different staining methods and apply in cases with various glomerular pathologic changes. Herein, pathologic images from renal biopsy slides stained with three basic special staining methods were used to build the data sets. The snapshot group included 1970 glomeruli from 516 patients, and the whole-slide image group included 8665 glomeruli from 148 patients. Cascade Mask region-based convolutional neural net architecture was trained to detect, classify, and segment glomeruli into three categories: i) GN, structural normal; ii) global sclerosis; and iii) glomerular with other lesions. In the snapshot group, total glomeruli, GN, global sclerosis, and glomerular with other lesions achieved an F1 score of 0.914, 0.896, 0.681, and 0.756, respectively, which were comparable with those in the whole-slide image group (0.940, 0.839, 0.806, and 0.753, respectively). Among the three categories, GN achieved the best instance segmentation effect in both groups, as determined by average precision, average recall, F1 score, and Mask mean Intersection over Union. The present model segments and classifies multistained glomeruli with efficiency and robustness. It can be applied as the first step for more detailed glomerular histologic analysis.

Lathyrane diterpenoids from Jatropha podagrica and their antitumor activities in human osteosarcoma cells.

Two new lathyrane-type diterpenoids, jatropodagins A and B (1 and 2), and five known analogues (3-7), were isolated from the stems of Jatropha podagrica. Their structures and absolute configurations were elucidated by spectroscopic data and calculated ECD analyses. The cytotoxicities of all the lathyrane-type diterpenoids (1-7) were evaluated against two human osteosarcoma cell lines (Saos-2 and MG-63). Compound 1 exhibited significant cytotoxic effects against Saos-2 and MG-63 with IC50 values of 8.08 and 14.64 µM, respectively. The IC50 values for the positive control 5-FU against the Saos-2 and MG-63 cell lines were 19.01 and 25.00 µM, respectively. Morphological features of apoptosis activities were evaluated in 1-treated Saos-2 cells and the results confirmed apoptosis in a dose-dependent manner.

Tuning the basicity of ionic liquids for efficient synthesis of alkylidene carbonates from CO2 at atmospheric pressure.

A strategy to achieve the efficient synthesis of alkylidene carbonates from CO2 at atmospheric pressure by tuning the basicity of ionic liquids was developed. Excellent yields were obtained due to basic ionic liquids' dual roles both as absorbents and as activators. The reaction mechanism was investigated through a combination of NMR spectroscopy, controlled experiments and quantum calculations, indicating the importance of a moderate basicity.

Protective effect of hydrogen-rich saline against radiation-induced immune dysfunction.

Recent studies showed that hydrogen can be used as an effective radioprotective agent through scavenging free radicals. This study was undertaken to evaluate the radioprotective effects of hydrogen on immune system in mice. H(2) was dissolved in physiological saline using an apparatus produced by our department. Spleen index and histological analysis were used to evaluate the splenic structural damage. Spleen superoxide dismutase, GSH, MDA were measured to appraise the antioxidant capacity and a DCF assay for the measurement of radical oxygen species. Cell apoptosis was evaluated by an Annexin V-FITC and propidium iodide staining method as well as the apoptotic proteins such as Bcl-2, Bax, caspase-3 and c-caspase-3. CD4+ and CD8+ T cells subtypes were detected by flow cytometry with FITC-labelled antimouse CD4 and PE antimouse CD8 staining. Real-time PCR was utilized to determine the CD4+ T cell subtypes and related cytokines. Our study demonstrated that pre-treatment with H(2) could increase the spleen index and attenuate the radiation damage on splenic structure. Radical oxygen species level was also reduced by H(2) treatment. H(2) also inhibited radiation-induced apoptosis in splenocytes and down-regulated pro-apoptotic proteins in living mice. Radiation-induced imbalance of T cells was attenuated by H(2). Finally, we found that H(2) could regulate the polarization of CD4+ T cells and the level of related cytokines. This study suggests H(2) as an effective radioprotective agent on immune system by scavenging reactive oxygen species.

Combined treatment of rituximab, idarubicin, dexamethasone, cytarabine, methotrexate with radiotherapy for primary central nervous system lymphoma.

The overall response rates and long-term survival of primary central nervous system lymphoma (PCNSL) are still significantly inferior to the results achieved in similar subtypes of extranodal non-Hodgkin's lymphoma. It is clearly necessary to investigate new therapeutic methods on PCNSL. We encountered three patients histologically documented PCNSL as diffuse large B-cell lymphoma (DLBCL). They were treated with R-IDARAM which comprised rituximab, idarubicin, dexamethasone, cytarabine and methotrexate. Patient 1 received stereotactic brachytherapy (SBT) prior to chemotherapy performed with iodine-125 seeds (cumulative therapeutic dose 50 Gy). After six cycles of R-IDARAM at 3-weekly intervals, radiotherapy was applied at a dosage of 2000-4000 cGy in conventional schedule (180 or 200 cGy/day) to whole brain or spinal cord in all patients. Complete remission (CR) was achieved after first two cycles of R-IDARAM in all patients. All three patients remained in CR at the time of this report with a median duration of follow-up of 23 months (ranging from 13 to 41 months). Three patients have been alive for 41, 13, 16 months respectively until now. The patient with the longest survival time was the one given SBT prior to chemotherapy. This study suggests that R-IDARAM combining with radiotherapy maybe a high effective regimen in PCNSL patients especially those with primary central nervous system DLBCL. A comprehensive treatment combining internal radiotherapy by SBT, modified R-IDARAM and followed reduced external radiotherapy may be a new treatment concept for PCNSL with higher efficiency and lower toxicity.

Hydrogen protects rats from dermatitis caused by local radiation.

BACKGROUND: Radiation therapy produced unwanted side effect on normal tissues, such as radiodermatitis. Hydrogen was previously shown capable of radiation protective in both animals and cell cultures. The effect of hydrogen was now to be investigated on radiation-induced cutaneous. OBJECTIVE: Development of dermatitis is a frequent side effect of radiotherapy of patients with head-and-neck cancer. Here we analyzed the radioprotective efficacy of hydrogen under conditions of local, single-dose or fractionated radiation treatment, and its possible molecular mechanisms. METHODS: Rats received either single-dose or fractioned irradiation of the head-and-neck area with or without subcutaneous injection of hydrogen solution before irradiation. In vitro, the effect of hydrogen medium on radiation-induced cell viability, apoptosis, and biochemical assays was measured. RESULT: Hydrogen significantly reduced the severity of dermatitis, accelerated tissue recovery, and reduced the extent of radiation-induced weight loss in rats after a single dose of 15 or 20 Gy but not 25 Gy of radiation. Hydrogen was also protective from cumulative doses of 30 Gy delivered in three fractions, respectively. Hydrogen also protect HaCaT cells from radiation-induced injury, it could significantly inhibit ionizing injury. CONCLUSION: These results suggest that hydrogen has a positive effect on acute radiodermatitis.

Therapeutic effects of hydrogen-rich solution on aplastic anemia in vivo.

BACKGROUND: Aplasitc anemia (AA) is a bone marrow failure syndrome characterized by an immune-mediated destruction of hematopoietic stem cells. Though clinical symptoms could be ameliorated by bone marrow transplantation and/or immunosuppressive therapy, frequent recurrence and especially evolution of clonal hematologic diseases remains problematic clinically. Cytokines such as interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secreted by autologous T cells are closely related with the development of AA. Hydrogen-rich solution was reported to inhibit the levels of cytokines including INF-γ, TNF-α and IL-6 in vivo in recent studies. This study was to investigate the potential therapeutic effects of hydrogen-rich solution on AA in vivo. METHODS: AA model was determined in vivo by mice and body weights of the mice were used as the basic physiological index. Peripheral blood cells were calculated to evaluate the hematologic recovery degree. Bone marrow nucleated cells (BMNCs), tissue histology, as well as CFU-S and CFU-GM forming units were used to evaluate the recovery of bone marrow microenvironment. The ratio of CD4(+) and CD8(+) cells were examined along with cytokine levels in serum to determine the efficacy of H2-rich solution on the affected immunological functions. RESULTS: Body weight and number of peripheral blood cells were significantly improved for mice in the H2-rich solution treated groups as compared with those with AA. The number of BMNCs and CFUs increased markedly and the bone marrow microenvironment was also improved significantly. The experimental group restrained the cell apoptosis, relieved hyperemia and accelerated tissue repair. The number of CD4(+) and CD8(+) cells as well as the ratio of CD4/CD8 increased to normal gradually, while the levels of TNF-α, IFN-γ, and IL-6 in serum decreased after H2-rich solution treatment. CONCLUSION: Our study firstly showed that hydrogen-rich solution accelerated the recovery of either hematological or immunological recovery on aplastic anemia mice. This finding suggests hydrogen-rich solution as a potential clinical therapeutic agent for AA.

Administration of hydrogen-rich saline protects mice from lethal acute graft-versus-host disease (aGVHD).

BACKGROUND: Allogeneic hematopoietic stem cell transplantation is a potentially curative therapy for many malignant and nonmalignant hematologic diseases. However, acute graft-versus-host disease (aGVHD) is a lethal complication of hematopoietic stem cell transplantation, which limits its application. Cytokines such as tumor necrosis factor-α and interleukin-6 play an extremely important role in the formation and development of aGVHD. Reactive oxygen species, such as hydroxyl radicals, also play an important role in the formation and development of aGVHD. In recent years, hydrogen was reported to have an ability to inhibit the levels of cytokines, such as tumor necrosis factor and interleukin-6 in vivo, and it also has a strong selective free radical-scavenging ability. Therefore, we hypothesized that hydrogen may have therapeutic effects on aGVHD. METHODS: To determine whether hydrogen could protect mice from lethal GVHD in a major histocompatibility complex-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated and leukocyte counts were also determined after BMT. We also examined serum cytokine levels and scored clinical signs of GVHD mice after BMT. RESULTS AND CONCLUSION: This article demonstrated that the administration of hydrogen-rich saline increased the survival rate and clinical score of aGVHD mice. Administration of hydrogen-rich saline after transplantation also promoted the recovery of white blood cells of aGVHD mice. However, there was no report on the therapeutic effects of hydrogen on aGVHD. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on aGVHD.

[Analysis of the risk factors related to prognosis of severe intra-abdominal infection in surgical intensive care unit].

OBJECTIVE: To investigate the risk factors related to prognosis of patients with severe intra-abdominal infection (SIAI) in surgical intensive care unit (SICU). METHODS: Clinical data of 69 patients with SIAI, who were hospitalized during January 2008 and April 2011 in SICU, were analyzed retrospectively. According to the outcome at discharge from SICU, 69 patients were divided into two groups: the survivors 42 cases; the deceased 27 cases. The potential risk factors of SIAI patients in SICU were analyzed by univariate analysis and logistic regression analysis. RESULTS: Univariate analysis showed that average acute physiology and chronic health evaluation II (APACHEII) scores (the survival group: 11.76 ± 3.48; the death group: 17.12 ± 4.50), inadequate treatment of intra-abdominal infection (3 survivors, 21 deceased), inadequate initial antibiotic treatment (3 survivors, 15 deceased) and septic shock (24 survivors, 27 deceased) were risk factors for mortality (all P < 0.01). Logistic regression analysis showed that average APACHEII scores over 15 [relative risk (RR): 6.846, P value: 0.044] and insufficient treatment of intra-abdominal infection (RR: 21.319, P value: 0.018) were the independent risk factors in SIAI patients in SICU. CONCLUSION: To decrease the mortality of SIAI patients in SICU, more attention should be paid to monitor APACHEII scores and to handle intra-abdominal infection adequately.