Identification of a novel prognostic signature based on vitamin metabolism clustering-related genes in lung adenocarcinoma.

Background: Vitamins, and their metabolic processes play essential regulatory roles in controlling proliferation, differentiation, and growth in carcinogenesis. However, the role of vitamin metabolism in lung adenocarcinoma (LUAD) has rarely been reported. Here, we established a novel prognostic model based on vitamin metabolism-related genes in LUAD. Methods: In this research, we aimed to identify vitamin metabolism associated with differentially expressed genes (DEGs) in LUAD utilizing The Cancer Genome Atlas (TCGA)-LUAD, GSE68465 and GSE72094 data. Unsupervised clustering classified patients into distinct subgroups. By utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis, vitamin metabolism-related genes could be used to construct prognostic model. Then the vitamin metabolism gene-related risk score (VRS) was calculated based on best cut-off splitting. Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) analysis, univariate and multivariate Cox analyses, chemotherapeutic drugs sensitivity analysis, immune infiltration analysis and nomogram were conducted to verify our models' accuracy. Finally, CPS1 was identified as a relevant diagnostic marker using Random Forests algorithms, single-cell RNA sequencing data was used to confirm its expression. Results: We investigated the relationship between vitamin metabolism patterns, overall survival (OS), and immune infiltration levels of patients with LUAD. A prognostic signature consisting of 11 genes was developed, which was able to classify patients into high and low VRS groups. Through gene enrichment analysis, cell cycle was mainly enriched. Compared to the low VRS group, the high VRS group exhibited poorer OS, as demonstrated by the Kaplan-Meier survival analysis. Furthermore, VRS was identified as an independent predictor of poor prognosis and poor OS, as indicated by both univariate and multivariate Cox regression analyses. Additionally, a nomogram was constructed to improve the accuracy of survival predictions in LUAD patients. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs. CPS1 was identified as a relevant diagnostic marker and the expression was also as confirmed by single-cell RNA sequencing data. Conclusions: Overall, our findings suggest that vitamin metabolism can influence the prognosis of LUAD patients, and our prognostic signature represents a potentially helpful resource for predicting patient outcomes and informing clinical decision-making.

Posterior circulation infarction after bronchial artery embolization.

Bronchial artery embolization is minimally invasive, has a low complication rate, and achieves good hemorrhage control. It is the first-line treatment in hemoptysis patients whom medications are ineffective. Cerebral infarction is a rare complication of bronchial artery embolization, with posterior circulation infarcts being the most common. Possible mechanisms include a neurotoxic reaction to the contrast medium used, bronchial artery-pulmonary shunt, embolus formation, fistula formation between the bronchial artery and the cerebral artery, and so on. To the best of our knowledge, there have been relatively few reports regarding posterior circulation infarcts after BAE, including 14 cases shown in Table 1. 11 patients recovered well after medical treatment, while the other patients did not survive. We report a case of a patient with a large posterior circulation infarct post bronchial artery embolization who developed severe neurological symptoms and died after 3 months of medication. Conclusion: Posterior circulation infarction is a rare but severe complication of bronchial artery embolization, and measures should be taken to prevent its occurrence.

KN026 (anti-HER2 bispecific antibody) in patients with previously treated, advanced HER2-expressing gastric or gastroesophageal junction cancer.

BACKGROUND: KN026 is a novel human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody that binds two distinct domains of HER2. We report the safety and efficacy results of the phase 2 trial in patients with advanced HER2-expressing gastric or gastroesophageal junction cancer who failed from at least one prior line of standard treatment. MATERIAL AND METHODS: In this open-label, multicentre, phase 2 trial, eligible patients were enrolled in the high-level HER2 cohort or low-level HER2 cohort and assigned to receive KN026 10 mg/kg (once a week), 20 mg/kg (once every two weeks) or 30 mg/kg (once every three weeks) intravenously. The primary end-points were the objective response rate (ORR) and duration of response assessed according to Response Evaluation Criteria in Solid Tumours (version 1.1). RESULTS: Between 17th June 2019 and 23rd August 2021, 45 patients were enrolled and received at least one dose of KN026, including 27 patients in the high-level HER2 cohort, 14 patients in the low-level HER2 cohort and four patients who had no HER2 expression. The ORR in the high-level HER2 cohort was 56% (95% confidence interval [CI] 35%-76%), with a durable response duration of 9.7 months (95% CI 4.2-not evaluable); while for the patients with low-level HER2, the ORR was 14% (95% CI 2%-43%). The most frequent ≥ grade 3 treatment-emergent adverse events were gastrointestinal disorders (five patients, 11%). No drug-related deaths were reported. CONCLUSIONS: KN026 showed a favourable safety profile and promising anti-tumour activity. Our results support further studies evaluating KN026 and the combination treatment with other active drugs in patients with advanced gastric or gastroesophageal junction cancer having high-level HER2 expression.

Correlation analysis between thromboelastography and liver injury related indexes in patients with heat stroke / 中国热带医学

@#Abstract: Objective To analyze the correlation between the thromboelastography (TEG) indexes and the indexes related to liver injury in patients with heat stroke, and explore the diagnostic value of TEG indexes for liver injury in patients with heat stroke. Methods A total of 95 patients with exertional heat stroke (EHS) admitted to 924 Hospital of the Joint Service Support Force of the People's Liberation Army of China from August 2020 to July 22 were selected, and divided into a non-liver injury group (55 cases) and a liver injury group (40 cases) according to whether there was liver injury. TEG instrument was used for the detection of thromboelastography to record the TEG parameters, including reaction time (R), agglutination time (K), α angle, maximum amplitude (MA value), and coagulation complex index (CI). The levels of glutamic transaminase (AST), alanine aminotransferase (ALT), total bilirubin (TBil), albumin (ALB) were detected by automatic biochemical analyzer. Pearson's method was applied to analyze the correlation between thromboelastography indexes R, K, α angle, CI and liver function indexes AST, ALT, TBil, ALB in patients with heat stroke after liver injury. Receiver operating characteristic curve (ROC) was applied to analyze the predictive value of thromboelastography indexes R, K, α angle, CI and combined detection for liver injury in patients with heat stroke. Results Compared with the non-liver injury group, the AST, ALT and TBil levels in patients with heat stroke in the liver injury group were higher (t=26.174, 16.923, 18.414, P<0.05), while the ALB level was lower (t=24.596, P<0.05); compared with the non-liver injury group, the R and K of patients with heat stroke in the liver injury group were higher (t=58.014, 52.862, P<0.05), and the α angle and CI were lower (t=46.853, 60.717, P<0.05); R was positively correlated with AST and ALT (r=0.532, 0.610, P<0.001), and negatively correlated with ALB (r=-0.551, P<0.001) in patients with heat stroke complicated with liver injury; K was positively correlated with AST, ALT and TBil (r=0.661, 0.531, 0.504, P<0.001); α angle was negatively correlated with AST and ALT (r=-0.473, -0.448, P<0.01), and positively correlated with ALB (r=0.539, P<0.001); CI was negatively correlated with AST, ALT and TBil (r=-0.458, -0.505, -0.549, P<0.001); the area under the curve (AUC) of thromboelastography indexes R, K, α angle and CI in predicting liver injury in patients with heat stroke was 0.807 (sensitivity of 70.0%, specificity of 81.6%), 0.831 (sensitivity of 77.5%, specificity of 85.5%), 0.747 (sensitivity of 67.5%, specificity of 74.5%), and 0.788 (sensitivity of 77.5%, specificity of 83.6%), respectively. The AUC of combined detection to predict liver injury in patients with heat stroke was 0.967 (sensitivity of 92.5%, specificity of 91.9%). Conclusions The thromboelastography indexes are correlated with the indexes related to liver injury in patients with heat stroke, and the thromboelastography indexes are helpful to diagnose liver injury in patients with heat stroke.

Role of SERCA3 in the Prognosis and Immune Function in Pan-Cancer.

The sarcoendoplasmic reticulum calcium adenosine triphosphatase (ATPase) 3 (SERCA3), a member of the SERCA protein family, is located at the endoplasmic reticulum. Its main function is to pump Ca2+ into the endoplasmic reticulum and is involved in maintaining intracellular calcium homeostasis and signal transduction, which are very important factors impacting cancer development and progression. However, the specific role of SERCA3 in cancer remains unclear. Our study, for the first time, comprehensively analyzed the SERCA3 expression profile in multiple cancers and its prognostic value in different cancers using bioinformatics. Furthermore, TCGA database was applied to evaluate the certain correlation of SERCA3 expression with immune modulator genes, immune checkpoints, immune cell infiltration, TMB, and MSI. The results revealed that in many cancers, SERCA3 expression was markedly decreased, which was related to poor prognosis. Additionally, we noticed that SERCA3 expression was correlated with TNM classification and WHO cancer stages in some cancer types. The Pearson correlation analysis showed that SERCA3 expression was closely associated with chemokines, chemokine receptors, MHC, immune activation genes, and immunosuppressive genes. In most cancer types, SERCA3 expression was also associated with immune checkpoints, including PDCD1 and CTLA-4. Further analysis suggested that SERCA3 was significantly correlated with CD8+ T cells, and regulatory T cells. Additionally, pan-cancer analysis confirmed that SERCA3 expression was related to TMB and MSI. In conclusion, these results offer a new insight into the functions and effects of SERCA3 in pan-cancer, and further provide some basis for considering SERCA3 as a potential cancer treatment target and biomarker.

Effect of Routine Therapy Assisted by Physical Exercise on Pulmonary Function in Patients with Asthma in Stable Stage: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Objective: This study is aimed at investigating the efficacy of physical exercise-assisted routine therapy on the pulmonary function of patients with stable asthma to provide clinical evidence and data support to guide disease management. Methods: Randomized controlled clinical trials of drug therapy and/or physical exercise for patients with stable asthma were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang database, Embase, PubMed, and Web of Science database. The studies published between January 2000 and June 2021 that met the criteria were included, and corresponding data were extracted. The meta-analysis was performed using the statistical software Stata 16.0. Statistical pooled effect sizes and 95% confidence intervals were calculated using a random-effects or fixed-effects model, as funnel plots were made with Begg's rank correlation method to evaluate publication bias. Result: This meta-analysis included 14 randomized controlled studies. Physical exercise-assisted treatment (experiment group) or routine therapy was associated with significantly elevated levels of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) (P < 0.05). As for the peak expiratory flow (PEF) level (P < 0.05), its level was significantly increased with physical exercise-assisted therapy compared with the conventional approach (P > 0.05). Subgroup analysis indicated that the FVC level in the experimental group was higher than that in the control group (P < 0.05) regardless of the adoption of aerobic exercise/anaerobic exercise. In regard to the FEV1 and PEE levels, aerobic exercise was associated with elevated levels in the experimental group (P < 0.05), while no significant difference in anaerobic exercise between both groups was observed (P > 0.05). Further, FEV1, FVC, and PEF levels in the experimental group were higher than those receiving conventional treatment in the control group (P < 0.05). Conclusion: Routine treatment combined with physical exercise could improve the levels of FEV1, FVC, and PEF in patients with bronchial asthma in the nonacute attack stage and enhance pulmonary functions. As a safe and efficient adjuvant therapy, physical exercise can contribute to an improved prognosis and quality of life for patients with asthma.

Long noncoding RNA OIP5-AS1 promotes the stemness of lung cancer cells through enhancing Oct4 mRNA stability.

Long noncoding RNA (lncRNA) OIP5-AS1 was shown to facilitate drug resistance and metastasis in several tumors. As cancer stem cells (CSCs) have been elucidated as the origin of drug resistance and tumor progression, we speculate that lncRNA OIP5-AS1 holds critical roles in the CSC-like traits of lung cancer. Here, lncRNA OIP5-AS1 was found to be highly expressed in lung cancer cell spheres. Following experiments showed that OIP-AS1 knockdown reduced the CSC-like traits of lung cancer spheres, while overexpression of OIP-AS1 conferred the CSC-like traits in lung cancer cells by performing sphere-formation analysis, detecting stemness marker expression, and ALDH activity. Mechanistic studies revealed that lncRNA OIP5-AS1 could increase Oct4 expression by directly interacting with Oct4 mRNA and enhancing Oct4 mRNA stability. Finally, we found that the knockdown of Oct4 could rescue the promoting effects of OIP5-AS1 overexpression on the CSC-like traits of lung cancer. These results demonstrate that lncRNA OIP5-AS1 can confer lung cancer CSC-like traits by directly interacting with Oct4 mRNA and thus increasing Oct4 mRNA stability and expression.

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential.

The coronavirus disease 2019 (COVID-19) pandemic has become a serious burden on global public health. Although therapeutic drugs against COVID-19 have been used in many countries, their efficacy is still limited. We here reported nanobody (Nb) phage display libraries derived from four camels immunized with the SARS-CoV-2 spike receptor-binding domain (RBD), from which 381 Nbs were identified to recognize SARS-CoV-2-RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin-converting enzyme 2 (ACE2) with SARS-CoV-2-RBD variants and two Nbs blocked the interaction of human ACE2 with bat-SL-CoV-WIV1-RBD and SARS-CoV-1-RBD. Among these candidates, Nb11-59 exhibited the highest activity against authentic SARS-CoV-2 with 50% neutralizing dose (ND50) of 0.55 µg/ml. Nb11-59 can be produced on large scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11-59 might be a promising prophylactic and therapeutic molecule against COVID-19, especially through inhalation delivery.

Antioxidant activities of Se-SPI produced from soybean as accumulation and biotransformation reactor of natural selenium.

A study to compare the uptake, translocation, and distribution of selenium (Se) in soybean planted in natural seleniferous soil in Fengcheng city of China was conducted to clarify the relationship between the Se content levels of soybean proteins and their radical scavenging activity. The data showed that the total Se content in different parts of soybean plants varied with the growth periods. The selenoprotein (Se-SPI) content increased remarkably with the increase of Se content in seleniferous soils. The Se-SPI content obtained from the region with the highest Se level was almost 18 times higher than that of the control group, while antioxidant activities were about 4-fold compared to the control, suggesting that Se played a positive role in enhancing the antioxidant activity of Se-SPI. The increase in the Se level also led to changes in amino acids composition, but with nearly no effects on the subunit composition of soybean Se-SPI.