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Background The prognosis of lung cancer varies widely, even in cases wherein the tumor stage, genetic mutation, and treatment regimens are the same. Thus, an effective means for risk stratification of patients with lung cancer is needed. Purpose To develop and validate a combined model for predicting progression-free survival and risk stratification in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treated with ensartinib. Material and Methods We analyzed 203 tumor lesions in 114 patients and evaluated average radiomic feature measures from all lesions at baseline and changes in these features after early treatment (Δradiomic features). Combined models were developed by integrating clinical with radiomic features. The prediction performance and clinical value of the proposed models were evaluated using receiver operating characteristic analysis, calibration curve, decision curve analysis (DCA), and Kaplan–Meier survival analysis. Results Both the baseline and delta combined models achieved predictive efficacy with a high area under the curve. The calibration curve and DCA indicated the high accuracy and clinical usefulness of the combined models for tumor progression prediction. In the Kaplan–Meier analysis, the delta and baseline combined models, Δradiomic signature, and two selected clinical features could distinguish patients with a higher progression risk within 42 weeks. The delta combined model had the best performance. Conclusion The combination of clinical and radiomic features provided a prognostic value for survival and progression in patients with NSCLC receiving ensartinib. Radiomic-signature changes after early treatment could be more valuable than those at baseline alone.

The high salt-alkalinity of bauxite residue (BR) hinders plant growth and revegetation of bauxite residue disposal areas (BRDA), which cause serious potential environmental and ecological risks. Bioneutralization is a promising method for improving the properties of BR and plant colonization. In the present study, a strong saline-alkali tolerant bacteria (ZH-1) was isolated from aged BR and identified as Bacillus sp. The medium of ZH-1 was optimized by orthogonal tests, and ZH-1 could decrease the medium pH from 11.8 to 6.01 (agitated culture) and 6.48 (static culture) by secretion of citric acid, oxalic acid and tartaric acid. With the inoculation of ZH-1, the pH of BR decreased from 11.6 to 8.76, and the water-soluble salt in BR increased by 68.11%. ZH-1 also changed the aggregate size distribution of BR, the mechanical-stable aggregates and water-stable aggregates increased by 18.76% and 10.83%, respectively. At the same time, the stability of the aggregates obviously increased and the destruction rate decreased from 94.37% to 73.46%. In addition, the microbial biomass carbon increased from 425 to 2794 mg/kg with the inoculation of ZH-1. Bacterial community analysis revealed that Clostridia, Bacilli, Gammaproteobacteria, Betaproteobacteria and Alphaproteobacteria were the main classes in the naturalized BR, and the inoculation of ZH-1 increased the diversity of bacteria in the BR. Overall, ZH-1 has great potential for neutralization and improvement the properties of BR and may be greatly beneficial for the revegetation of BRDA.

Background There are many factors that lead to dwarfism, and the mechanism has not yet been elucidated. Next-generation sequencing may identify candidate-related gene mutations, which may clarify the molecular cause. Aim To analyze genetic variation by using a constructed panel related to dwarfism by utilizing next-generation sequencing platform sequencing analysis to screen candidate-related gene mutations. Methods Physical and laboratory characteristics, including clinical examination, growth hormone drug challenge test, serum insulin-like growth factor-1 (IGF-1), IGF binding protein 3, other related tests, imaging examination, and chromosome karyotyping, were analyzed. Next-generation sequencing was performed to analyze pathogenicity variability. Results In the 39 dwarfism patients, 10 had pathogenicity variability. Gene variation was found in the OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes. Of the 10 patients with pathogenicity variability, the related physical characteristics included double breast development and growth hormone deficiency, enuresis and indirect inguinal hernia on the left, two finger distance of 70.2 cm, head circumference of 49.2 cm, ischium/lower body length of 1.8 cm, weak limb muscles, and partial growth hormone deficiency. After 6 mo of growth hormone therapy, the concentrations of IGF-1 and IGF binding protein 3 increased from 215.2 ± 170.3 to 285.0 ± 166.0 and 3.9 ± 1.4 to 4.2 ± 1.1, respectively. Conclusion OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes may be related to the incidence of dwarfism, and more research needs to be performed to elucidate the mechanism.

Acne vulgaris is one of the most common dermatological diseases. Some topical treatments for acne used in combination, such as blue light and topical antibiotics (such as metronidazole) by needle-free jet injection (NFJI), are becoming prevalent in clinical practice, but the efficacy remains uncertain.In order to investigate the effect of blue light combined with metronidazole by NFJI in the treatment of acne, the 251 enrolled patients were randomly assigned into the blue light group, metronidazole (MNZ) group, and MNZ + blue light group, and then received 6-weeks' treatment. A variety of objective and subjective methods such as clinical pictures, skin barrier physiological parameters (including trans-epidermal water loss (TEWL), stratum corneum hydration, facail surface sebum, erythema and pigmentation), the Investigator Global Assessment score, acne lesion count assessment, Patients' Self-Assessment, and VAS score were used to evaluate the efficacy and side effects of the treatments.Compared to the baseline, the MNZ + blue light group showed significant improvement in acne lesion count reduction, TEWL, straum corneum hydration, facial surface sebum and erythema (p 0.05). The MNZ + blue light group showed significant differences compared with the MNZ group and blue light group in terms of acne lesion count reduction and erythema (p 0.05) Compared to the MNZ group, the MNZ + blue light group demonstrated significant improvement in TEWL and sebum (p 0.05). While compared to the blue light group, the MNZ + blue light group showed significant improvement in hydration (p 0.05). There was no statistically significant difference among the three groups in pigmentation (p 0.05).The combination of MNZ by NFJI and blue light has a synergistic effect and can relieve acne skin lesion within 6 weeks in the treatment of moderate and moderate-to-severe facial acne vulgaris, meanwhile, this method has a good safety.

Recent evidences have suggested that genistein, a beneficial isoflavonoid, exerts marked anti-proliferative action on colorectal cancer (CRC) cells. However, the exact molecular mechanisms behind anti-CRC effect of genistein have not been elucidated. In current report, a systemic pharmacology analysis was used to disclose the anti-CRC mechanism of genistein prior to performing experimentative certification. As shown in network pharmacology findings, a total of 189 common targets and 9 hard-core targets of genistein-anti-CRC were collected and identified. And the detailed anti-CRC functions and pathways mediated by genistein were uncovered. In further certification, human CRC samples resulted in elevated protein and mRNA expressions of myeloid leukemia cell differentiation protein (MCL1), beta amyloid A4 protein (APP), and vascular endothelial growth factor receptor 2 (KDR). In animal experiment, genistein-treated tumor-transplanted nude mice exhibited reduced tumor growth, accompanied with dose-dependent down-regulations of MCL1, APP, and KDR proteins and mRNAs. Taken together, the integrated bioinformatic and experimental findings uncover the anti-CRC mechanisms and targets mediated by genistein. Significantly, parts of hard-core biotargets were experimentally verified before clinical application, including MCL1, APP, and KDR.

Yi Liang,1 Lv Lv,2 Liang He,1 Wei Deng,3 Cai Chen,1 Jingjuan Li1 1Department of Anesthesiology, The Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 2Emergency Department, The Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 3Department of Anesthesiology, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, People’s Republic of ChinaCorrespondence: Liang HeDepartment of Anesthesiology, The Affiliated Hospital of Guilin Medical University, Lequn Road 15#, Guilin 541001, People’s Republic of ChinaTel +8613659633168Email jimyliang@hotmail.comBackground and Objectives: Patients with femoral neck fractures often suffer severe pain. This randomized controlled clinical study compared the effect of femoral nerve block (FNB) and fascia iliaca compartment block (FICB) in this population.Patients and Methods: Forty-six patients were randomly assigned to one of the two groups: FNB group (femoral nerve block, n=23) or FICB group (fascia iliaca compartment block, n=23). Before positioning for spinal anesthesia, patients received FNB with 15 mL of 0.5% ropivacaine or FICB with 40 mL of 0.5% ropivacaine. Pain was evaluated using a visual analogue scale (VAS) at rest and during hip flexion after admission to the operation room; at 3, 5, 8, and 10 min after analgesia intervention; and during positioning for spinal anesthesia. Positioning was attempted after 10 min of analgesia intervention in each group. Time required to perform spinal anesthesia, quality of positioning, and patient satisfaction were documented.Results: The VAS scores in the FNB group were significantly lower than those in FICB group at 3 and 5 min after analgesia intervention (P=0.000). However, there were no significant differences in VAS between groups at 8 or 10 min or during positioning.Conclusion: FNB and FICB produce similar analgesic effects in patients with femoral neck fractures, but FNB has a more rapid onset of pain relief.Keywords: femoral neck fracture, femoral nerve block, fascia iliaca compartment block, analgesia

Background and objectives Patients with femoral neck fractures often suffer severe pain. This randomized controlled clinical study compared the effect of femoral nerve block (FNB) and fascia iliaca compartment block (FICB) in this population. Patients and methods Forty-six patients were randomly assigned to one of the two groups: FNB group (femoral nerve block, n=23) or FICB group (fascia iliaca compartment block, n=23). Before positioning for spinal anesthesia, patients received FNB with 15 mL of 0.5% ropivacaine or FICB with 40 mL of 0.5% ropivacaine. Pain was evaluated using a visual analogue scale (VAS) at rest and during hip flexion after admission to the operation room; at 3, 5, 8, and 10 min after analgesia intervention; and during positioning for spinal anesthesia. Positioning was attempted after 10 min of analgesia intervention in each group. Time required to perform spinal anesthesia, quality of positioning, and patient satisfaction were documented. Results The VAS scores in the FNB group were significantly lower than those in FICB group at 3 and 5 min after analgesia intervention (P=0.000). However, there were no significant differences in VAS between groups at 8 or 10 min or during positioning. Conclusion FNB and FICB produce similar analgesic effects in patients with femoral neck fractures, but FNB has a more rapid onset of pain relief.

Supplemental material, sj-doc-1-acr-10.1177_02841851221119621 for Radiomic-signature changes after early treatment improve the prediction of progression-free survival in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer by Donghui Hou, Xiaomin Zheng, Wei Song, Xiaoqing Liu, Sicong Wang, Lina Zhou, Xiuli Tao, Lv Lv, Qi Sun, Yujing Jin, Zewei Zhang, Lieming Ding, Ning Wu and Shijun Zhao in Acta Radiologica

Shaohua Chen,1,2 Ziyao Jin,3 Linfeng Xin,4 Lv Lv,2 Xuemei Zhang,3 Yizhen Gong,5 Jianlun Liu1 1Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nangning, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 4Clinical Medicine, Guilin Medical University, Guilin, People’s Republic of China; 5Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nangning, People’s Republic of ChinaCorrespondence: Jianlun Liu Email 631228181@qq.comObjective: We aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC).Methods: Kaplan–Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan–Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC.Results: ORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration.Conclusion: ORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.Keywords: origin recognition complex, breast cancer, prognostic biomarker, nomogram, gene set enrichment analysis, immune infiltration

BackgroundThe aim of this study is to investigate the potential clinical and prognostic value, role and driving molecular mechanisms of the origin recognition complex family in breast cancer.Resultsata from Oncomine, TCGA, GEO and ULCAN showed that ORC1L and ORC6L were highly expressed in breast cancer tissues, while the expression of ORC5L was inconsistent and there was no significant difference in the expression of ORC2L, ORC3L and ORC4L. High expression of ORC1L and ORC6L were mainly Her2 overexpressed subtype, and their expression were negatively correlated with patient age and positively correlated with tumor size, but not with lymph node metastasis, distant metastasis, or tumor stage. Expression of ORC5L was also negatively correlated with age and positively correlated with lymph node metastasis, but not with breast cancer molecular subtype and tumor size. Expression of ORC1L and ORC5L had high diagnostic value, and ORC6L had the highest diagnostic value in breast cancer. ORC6L was an independent poor prognostic factor for overall survival of breast cancer patients. It was involved in cell cycle progression, cell senescence, epigenetic regulation and other biological functions, and may regulate signaling pathways such as NF-KB, TP53 and WNT in breast cancer. We also found that the expression of ORC6L was related to the increased infiltration of Th1/2 cell and Treg cell, and decreased infiltration of Mast cell and NK cell.ConclusionsORC1L and ORC6L are highly expressed in breast cancer tissues, of which ORC6L has high diagnostic value and is an independent poor prognostic factor for overall survival of breast cancer patients. ORC6L may be involved in the occurrence and progression of breast cancer by regulating cell cycle progression, promoting the activation of cancer signaling pathways, and influencing tumor immune cells infiltration.

Computed tomography (CT) imaging can help to predict the pathological invasiveness of early-stage lung adenocarcinoma and guide surgical resection. This retrospective study investigated whether CT imaging could distinguish pre-invasive lung adenocarcinoma from IAC. It also compared final pathology prediction accuracy between CT imaging and intraoperative frozen section analysis.This study included 2093 patients with early-stage peripheral lung adenocarcinoma who underwent CT imaging and intraoperative frozen section analysis between March 2013 and November 2014. Nodules were classified as ground-glass (GGNs), part-solid (PSNs), and solid nodules according to CT findings; they were classified as pre-IAC and IAC according to final pathology. Univariate, multivariate, and receiver operating characteristic (ROC) curve analyses were performed to evaluate whether CT imaging could distinguish pre-IAC from IAC. The concordance rates of CT imaging and intraoperative frozen section analyses with final pathology were also compared to determine their accuracies.Multivariate analysis identified tumor size as an independent distinguishing factor. ROC curve analyses showed that the optimal cut-off sizes for distinguishing pre-IAC from IAC for GGNs, PSNs, and solid nodules were 10.79, 11.48, and 11.45 mm, respectively. The concordance rate of CT imaging with final pathology was significantly greater than the concordance rate of intraoperative frozen section analysis with final pathology (P = 0.041).CT imaging could distinguish pre-IAC from IAC in patients with early-stage lung adenocarcinoma. Because of its accuracy in predicting final pathology, CT imaging could contribute to decisions associated with surgical extent. Multicenter standardized trials are needed to confirm the findings in this study.

Background Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression‐free survival (PFS). Methods We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. We also established a multifactorial model of clinicopathological and quantitative CT radiomic features to predict PFS and risk stratification. Kaplan–Meier analysis was conducted to identify risk factors for tumor progression. Results Univariate analysis indicated a statistical difference (p = 0.035) in PFS among ALK variants in three classifications (V1, V3, and other variants). Secondary ALK alterations were adversely associated with PFS both in univariate (p = 0.008) and multivariate (p = 0.04) analyses and could identify patients at high risk for early progression in the Kaplan–Meier analysis (p = 0.002). Additionally, response duration to crizotinib, The secondary ALK alterations were adversely associated with ensartinib response duration in NSCLC, and ALK variants might not correlate with PFS. CT quantitative radiomic signature could add prognostic prediction value of clinicopathological features.

Ebola virus (EBOV) infection leads to staggeringly high mortality rates. Effective and low-cost treatments are urgently needed to control frequent EBOV outbreaks in Africa. In this study, we report that a natural compound called berbamine hydrochloride strongly inhibits EBOV replication in vitro and in vivo. Our work further showed that berbamine hydrochloride acts by direct binding to the cleaved EBOV glycoprotein (GPcl), disrupting GPcl interaction with viral receptor NPC1, thus blocking the fusion of viral and cellular membranes. Our data support the probability of developing anti-EBOV small molecule drugs by targeting viral GPcl. More importantly, since berbamine hydrochloride has been used in clinic to treat leukopenia, it holds great promise of being quickly repurposed as an anti-EBOV drug.

Background: The inflammatory reaction is the main cause of acute respiratory distress syndrome and multiple organ failure in patients with Coronavirus disease 2019, especially those with severe and critical illness. Several studies suggested that high-dose vitamin C reduced inflammatory reaction associated with sepsis and acute respiratory distress syndrome. This study aimed to determine the efficacy and safety of high-dose vitamin C in Coronavirus disease 2019. Methods: We included 76 patients with Coronavirus disease 2019, classified into the high-dose vitamin C group (loading dose of 6g intravenous infusion per 12 hr on the first day, and 6g once for the following 4 days, n=46) and the standard therapy group (standard therapy alone, n=30). Results: The risk of 28-day mortality was reduced for the high-dose vitamin C versus the standard therapy group (HR=0.14, 95% CI, 0.03-0.72). Oxygen support status was improved more with high-dose vitamin C than standard therapy (63.9% vs 36.1%). No safety events were associated with high-dose vitamin C therapy. Conclusion: High-dose vitamin C may reduce the mortality and improve oxygen support status in patients with Coronavirus disease 2019 without adverse events.

Purpose The aim of the present study was to investigate predictors of pathological invasiveness and prognosis of lung adenocarcinoma in patients with pure ground-glass nodules (pGGNs). Methods Clinical and computed tomography (CT) features of invasive adenocarcinomas (IACs) and pre-IACs were retrospectively compared in 641 consecutive patients with pGGNs and confirmed lung adenocarcinomas who had been followed up by CT postoperatively, and potential predictors of prognosis were investigated. Results Of 659 pGGNs in 641 patients, 258 (39.1%) were adenocarcinomas in situ, 265 (40.2%) were minimally invasive adenocarcinomas, and 136 (20.6%) were IACs. Respective optimal cutoffs for age, serum carcinoembryonic antigen, maximal diameter, mean diameter, and CT density for distinguishing preIACs from IACs were 53 years, 2.19 ng/mL, 10.78 mm, 10.09 mm, and − 582.28 Hounsfield units (HU). In univariable analysis sex, age, maximal diameter, mean diameter, CT density, and spiculation were significant predictors of lung IAC. In multivariable analysis age, maximal diameter, and CT density were significant predictors of lung IAC. During a median follow-up of 41 months no pGGN IACs recurred. Conclusions pGGNs may be lung IACs, especially in patients aged > 55 years with lesions that are > 1 cm in diameter and exhibit CT density > − 600 HU. pGGN IACs of