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Objectives. Nicotine is an ingredient of tobacco, and exposure to nicotine increases the risks of various cancers, including oral cancer. Previous studies have focused on the addictive properties of nicotine, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process through which nicotine promotes the occurrence and development of oral cancer via data mining and experimental verification.Methods. This study involved three parts. First, key genes related to nicotine-related oral cancer were screened through data mining; second, the expression and clinical significance of a key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.Results. SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways, such as the tumor necrosis factor and apelin pathways, and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to bleomycin and docetaxel.Conclusion. This study revealed SERPINE1 as a key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.

Deep neural networks have achieved remarkable success in HEVC compressed video quality enhancement. However, most existing multiframe-based methods either deliver unsatisfactory results or consume a significant amount of resources to leverage temporal information of neighboring frames. For the sake of practicality, a thorough investigation of the architecture design of the video quality enhancement network regarding enhancement performance, model parameters, and running speed is essential. In this article, we first propose an efficient alignment module that can quickly and accurately aggregate the spatiotemporal information of neighboring frames. The proposed module estimates deformable offsets progressively in lower-resolution space motivated by the observation of offset correlations between adjacent pixels. Then, the quantization parameter (QP) that represents compression level prior knowledge is utilized to guide aligned feature enhancement. By combining alignment feature distillation with residual feature correction, we obtain an efficient QP attention block. To save the storage space of the network, we design a hash buffer to store QP embedding features. These efficient components allow our network to effectively exploit temporal redundancies and obtain favorable enhancement capability while maintaining a lightweight structure and fast running speed. Extensive experiments demonstrate that the proposed approach outperforms state-of-the-art methods over different QPs by up to 0.09 to 0.11 dB, whereas the inference time can be reduced by up to 69%.

The goals of carbon peak and carbon neutrality have put forward higher requirements for the low-carbon development of power supply. This paper discusses the impacts of multi-energy power generation on carbon emissions for 30 regions in China and proposes low-carbon development suggestions for the electric power industry. The research found that firstly there is a significant strong positive correlation between thermal power and carbon emissions in most regions of China, so the carbon emission reduction of power supply should still focus on thermal power. Secondly, wind power and photovoltaic power have positive effects or negative effects on carbon emissions in different regions. But combined with the analysis results in regions with the rapid development of wind power or photovoltaic power, it could be found that wind power and photovoltaic power contributed to reducing carbon emissions when they developed to a certain scale. It is proposed to speed up the construction of wind power and photovoltaic power in regions with rich wind resources or solar resources such as Inner Mongolia, Xinjiang, Liaoning, and Gansu. Thirdly, hydropower and nuclear power both have negative effects on carbon emissions. Considering the large demand for electricity in coastal regions where nuclear power is located, it is suggested that coastal regions should gradually promote the construction and application of nuclear power on the basis of safety.

Reducing exhaust emissions, promoting economic development, and realizing clean energy utilization have always been concerns in China. To measure the relationship between them, this study selects the data related to energy consumption, economic growth, and exhaust emissions from 2000 to 2019 in 30 Chinese provinces. By constructing a panel vector autoregressive (PVAR) model, the dynamic relationship between them in China is quantitatively analyzed. The results show that there is a long-term interaction between energy consumption, economic growth, and exhaust emissions. Among them, economic growth is highly dependent on energy consumption, but it can promote the reduction of exhaust emissions. However, energy consumption will produce a large amount of industrial waste, such as sulfur dioxide and carbon dioxide emissions. Specifically, the industrial structure and energy structure have the most obvious impact on reducing industrial sulfur dioxide emissions and carbon emissions, with the proportion between 0.071-0.090 and 0.031-0.032, respectively. Therefore, the adjustment of industrial structure and energy structure is the key to exhaust emission reduction.

Chinese herbal slices (CHSs) are closely associated to microorganisms, whether they are endophytic or epiphytic in plants, or introduced during processing. In this study, the structures and predicted functions of microbial communities in 150 batches of samples from five types of CHSs were investigated by combining pure culture and 16 S rDNA amplicon sequencing. Bile-salt-tolerant gram-negative bacteria were detected in 56.0% of samples, andThe online version contains supplementary material available at 10.1007/s11756-022-01199-0.

OBJECTIVE Opioid-minimizing or nonopioid therapy using nonsteroidal antiinflammatory drugs (NSAIDs) or tramadol has been encouraged for pain management. This study aimed to examine the noninferiority of NSAIDs to tramadol for pain management following transsphenoidal surgery for pituitary adenomas in terms of analgesic efficacy, adverse events, and rescue opioid use. METHODS This was a randomized, single-center, double-blind noninferiority trial. Patients 18–70 years old with planned transsphenoidal surgery for pituitary adenomas were randomly assigned (in a 1-to-1 ratio) to receive NSAIDs (parecoxib injection and subsequent loxoprofen tablets) or tramadol (tramadol injection and subsequent tramadol tablets). The primary outcome was pain score assessed by a visual analog scale (VAS) for 24 hours following surgery; the secondary outcomes were VAS scores for 48 and 72 hours. Other prespecified outcomes included nausea, vomiting, dizziness, upset stomach, skin rash, peptic ulcer, gastrointestinal bleeding, and pethidine use to control breakthrough pain. Noninferiority of NSAIDs to tramadol was established if the upper limit of the 95% confidence interval (CI) of the VAS score difference was < 1 point and the rate difference of adverse events and pethidine use < 5%. The superiority of NSAIDs was assessed when noninferiority was verified. All analyses were performed on an intention-to-treat basis. RESULTS Two hundred two patients were enrolled between November 1, 2020, and May 31, 2021 (101 in the NSAIDs group, 101 in the tramadol group). Baseline characteristics between groups were well balanced. Mean VAS scores for 24 hours following transsphenoidal surgery were 2.6 ± 1.8 in the NSAIDs group and 3.5 ± 2.1 in the tramadol group (−0.9 difference, 95% CI −1.5 to −0.4; p value for noninferiority < 0.001, p value for superiority < 0.001). Noninferiority and superiority were also achieved for both secondary outcomes. VAS scores improved over time in both groups. Incidences of nausea (39.6% vs 61.4%, p = 0.002), vomiting (3.0% vs 42.6%, p < 0.001), and dizziness (12.9% vs 47.5%, p < 0.001) were significantly lower, while incidence of upset stomach (9.9% vs 2.0%, p = 0.017) was slightly higher in the NSAIDs group compared with the tramadol group. The percentage of opioid use was 4.0% in the NSAIDs group and 15.8% in the tramadol group (−11.8% difference, 95% CI −19.9% to −3.7%; p value for noninferiority < 0.001, p value for superiority = 0.005). CONCLUSIONS NSAIDs significantly reduced acute pain following transsphenoidal surgery, caused few adverse events, and limited opioid use compared with tramadol.

BackgroundThe World Health Organization (WHO) CNS5 classification system highlights the significance of molecular biomarkers in providing meaningful prognostic and therapeutic information for gliomas. However, predicting individual patient survival remains challenging due to the lack of integrated quantitative assessment tools. In this study, we aimed to design a WHO CNS5-related risk signature to predict the overall survival (OS) rate of glioma patients using machine learning algorithms.MethodsWe extracted data from patients who underwent an operation for histopathologically confirmed glioma from our hospital database (2011–2022) and split them into a training and hold-out test set in a 7/3 ratio. We used biological markers related to WHO CNS5, clinical data (age, sex, and WHO grade), and prognosis follow-up information to identify prognostic factors and construct a predictive dynamic nomograph to predict the survival rate of glioma patients using 4 kinds machine learning algorithms (RF, SVM, XGB, and GLM).ResultsA total of 198 patients with complete WHO5 molecular data and follow-up information were included in the study. The median OS time of all patients was 29.77 [95% confidence interval (CI): 21.19–38.34] months. Age, FGFR2, IDH1, CDK4, CDK6, KIT, and CDKN2A were considered vital indicators related to the prognosis and OS time of glioma. To better predict the prognosis of glioma patients, we constructed a WHO5-related risk signature and nomogram. The AUC values of the ROC curves of the nomogram for predicting the 1, 3, and 5-year OS were 0.849, 0.835, and 0.821 in training set, and, 0.844, 0.943, and 0.959 in validation set. The calibration plot confirmed the reliability of the nomogram, and the c-index was 0.742 in training set and 0.775 in validation set. Additionally, our nomogram showed a superior net benefit across a broader scale of threshold probabilities in decision curve analysis. Therefore, we selected it as the backend for the online survival prediction tool (Glioma Survival Calculator, https://who5pumch.shinyapps.io/DynNomapp/), which can calculate the survival probability for a specific time of the patients.ConclusionAn online prognosis predictor based on WHO5-related biomarkers was constructed. This therapeutically promising tool may increase the precision of forecast therapy outcomes and assess prognosis.

IntroductionThe fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors released in 2021 formally defines pediatric-type diffuse gliomas. However, there is still little understanding of pediatric-type diffuse gliomas, and even less attention has been paid to adult patients. Therefore, this study describes the clinical radiological, survival, and molecular features of adult patients with pediatric-type glioma.MethodsAdult patients who underwent surgery from January 2011 to January 2022, classified as pediatric-type glioma, were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis.ResultsAmong 596 adult patients, 20 patients with pediatric-type glioma were screened, including 6 with diffuse astrocytoma, MYB- or MYBL1-altered, 2 with diffuse midline glioma, H3 K27-altered, and 12 with diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. Pediatric high-grade glioma (pHGG) frequently showed tumor enhancement, peritumoral edema, and intratumoral necrosis. Adult patients with pHGG showed a longer life expectancy than adult patients with glioblastoma. Common molecular alterations included chromosome alterations and CDKN2A/B, PIK3CA, and PTEN, while altered KMT5B and MET were found to affect the overall survival.ConclusionOur study demonstrated adult patients with pediatric-type glioma. Notably, our research aims to expand the current understanding of adult patients with pediatric-type diffuse gliomas. Furthermore, personalized therapies consisting of targeted molecular inhibitors for MET and VEGFA may exhibit beneficial effects in the corresponding population.

Purpose Cognitive impairment is a common feature among patients with diffuse glioma. This study aimed to investigate the relationship between cognitive function and clinical and molecular factors under the new 2021 WHO classification of tumors of the central nervous system (CNS 5). Methods A total of 110 patients with diffuse glioma were enrolled and underwent preoperative cognitive assessments using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Clinical information was collected from medical records, and gene sequencing was performed to analyze 18 most influenced gene alterations. The differences in cognitive function between patients with and without glioblastoma were compared under both CNS 4 and CNS 5 to assess the effect of differentiation on cognition. Results The study found that age, tumor location, and glioblastoma had significant differences on cognitive function. Several genetic alterations were significantly correlated with cognition. For most focused genes, patients with a low number of genetic alterations tended to have better cognitive function. Conclusion Our study suggested that, in addition to general clinical characteristics such as age, histological type and tumor location, the molecular characteristics of glioma play a crucial role in cognitive function. Further research into the mechanisms by which tumors affect brain function is expected to enhance the quality of life for glioma patients. The findings of this study highlight the importance of considering both clinical and molecular factors in the management of glioma patients to improve cognitive outcomes.

BackgroundThe 5th edition of the World Health Organization (WHO) classification of central nervous system tumors incorporated specific molecular alterations into the categorization of gliomas. The major revision of the classification scheme effectuates significant changes in the diagnosis and management of glioma. This study aimed to depict the clinical, molecular, and prognostic characteristics of glioma and its subtypes according to the current WHO classification.MethodsPatients who underwent surgery for glioma at Peking Union Medical College Hospital during 11 years were re-examined for tumor genetic alterations using next-generation sequencing, polymerase chain reaction-based assay, and fluorescence in situ hybridization methods and enrolled in the analysis.ResultsThe enrolled 452 gliomas were reclassified into adult-type diffuse glioma (ntotal=373; astrocytoma, n=78; oligodendroglioma, n=104; glioblastoma, n=191), pediatric-type diffuse glioma (ntotal=23; low-grade, n=8; high-grade, n=15), circumscribed astrocytic glioma (n=20), and glioneuronal and neuronal tumor (n=36). The composition, definition, and incidence of adult- and pediatric-type gliomas changed significantly between the 4th and the 5th editions of the classification. The clinical, radiological, molecular, and survival characteristics of each subtype of glioma were identified. Alterations in CDK4/6, CIC, FGFR2/3/4, FUBP1, KIT, MET, NF1, PEG3, RB1, and NTRK2 were additional factors correlated with the survival of different subtypes of gliomas.ConclusionsThe updated WHO classification based on histology and molecular alterations has updated our understanding of the clinical, radiological, molecular, survival, and prognostic characteristics of varied subtypes of gliomas and provided accurate guidance for diagnosis and potential prognosis for patients.

Acromegaly is a chronic progressive endocrine disease that is often accompanied by joint and bone symptoms. The correlation between bone metabolism and acromegaly is still unclear. In this study, 31 patients with acromegaly at Peking Union Medical College Hospital were included. Bone metabolism indices, such as β-CTX, TP1NP, T-25OHD, 1,25(OH)2D3, and SAGIT score, which represent the severity of acromegaly, were examined before operation, and the patients were followed up for at least 3 months after operation. The results showed that β-CTX and TP1NP were significantly lower than those before surgery in the remission group (p 0.001). In the nonremission group, CTX (p = 0.226) and TP1NP (p = 0.326) did not show significant differences from those before operation. In Pearson correlation analysis, β-CTX was significantly correlated with SAGIT score (r = 0.356, p = 0.049). By multivariate linear regression analysis, it was found that β-CTX was an independent risk factor of SAGIT score (p = 0.001). In conclusion, indicators of bone metabolism are closely related to changes in acromegaly, and the β-CTX value can be used as an effective predictor for assessing acromegaly.

Recently, many researches on convolution neural network (CNN) based in-loop filters have been proposed to improve coding efficiency. However, most existing CNN based filters tend to train and deploy multiple networks for various quantization parameters (QP) and frame types (FT), which drastically increases resources in training these models and the memory burdens for video codec. In this paper, we propose a novel variable CNN (VCNN) based in-loop filter for VVC, which can effectively handle the compressed videos with different QPs and FTs via a single model. Specifically, an efficient and flexible attention module is developed to recalibrate features according to QPs or FTs. Then we embed the module into the residual block so that these informative features can be continuously utilized in the residual learning process. To minimize the information loss in the learning process of the entire network, we utilize a residual feature aggregation module (RFA) for more efficient feature extraction. Based on it, an efficient network architecture VCNN is designed that can not only effectively reduce compression artifacts, but also can be adaptive to various QPs and FTs. To address training data imbalance on various QPs and FTs and improve the robustness of the model, a focal mean square error loss function is employed to train the proposed network. Then we integrate the VCNN into VVC as an additional tool of in-loop filters after the deblocking filter. Extensive experimental results show that our VCNN approach obtains on average 3.63%, 4.36%, 4.23%, 3.56% under all intra, low-delay P, low-delay, and random access configurations, respectively, which is even better than QP-Separate models.

Aim. The destruction of the vascular endothelial barrier mediated by Ox-LDL is the initial link to atherosclerosis. Here, we aimed to determine whether the immunological intervention with Ox-ApoB polypeptide fragment (Ox-ApoB-PF) can block the deposition of Ox-LDL in vascular endothelial cells through LOX-1 receptors, thereby protecting the barrier function and survival status of vascular endothelial cells and inhibiting the progression of atherosclerosis. Methods and Results. In order to determine the harm of Ox-LDL to vascular endothelial cells and the protective effect of immune intervention with Ox-ApoB-PF, we conducted a series of corresponding experiments in vitro and in vivo. The in vitro results showed that Ox-LDL can activate endothelial cell apoptosis pathway; reduce the expression of endothelial junction proteins; affect the migration, deformation, and forming ability; and ultimately destroy the vascular endothelial barrier function. The increased permeability of endothelial cells led to a sharp increase in the phagocytosis of Ox-LDL by macrophages under the endothelial layer. Meanwhile, Ox-LDL stimulation induced a significant upregulation of LOX-1 in endothelial cells and increased the expression of endothelial cell chemokines and adhesion factors. Ox-ApoB-PF antibodies can significantly reduce the abovementioned harmful effects. The in vivo results showed that active immune intervention through Ox-ApoB-PF can protect the endothelial barrier function; reduce macrophage deposition and the inflammatory response in plaques; alleviate lipid deposition in the plaques, as well as apoptosis and necrosis; and increase the ability of liver macrophages to clear Ox-LDL. Eventually, the progression of plaque and the formation of necrotic cores in plaques can be inhibited. Conclusions. An Ox-ApoB-PF antibody may protect the endothelial cell physiological function and survival status by blocking the combination of Ox-LDL/LOX-1 in vascular endothelial cells. Immune intervention with Ox-ApoB-PF inhibits the occurrence and development of atherosclerotic lesions by protecting the vascular endothelial barrier function.

Exosomes are small extracellular vesicles that carry various bioactive molecules including various RNAs that modulate the activities of recipient cells. It has drawn considerable attention as means of cell communication and drug delivery. Exosome plays important role in various tumors, but it is rarely summarized in pituitary adenoma (PA). PA is the second most common primary central nervous system tumor, and its recurrence and persistent postoperative hormone hypersecretion lead to compromised quality of life. How exactly exosomes impact tumor development and hormone secretion is important for the development of this tumor diagnosis and treatment. In this review, we discuss how exosomal RNAs impact PAs and their potential as future clinical therapies. In our literature review, first, we found that exosomal microRNA hsa-miR-1180-3p is a potential early biomarker for NFPAs. Since NFPAs are typically difficult to diagnose, this is an especially important finding. Second, exosomal protein transcripts are potential invasive biomarker, such as MMP1, N-cadherin, CDK6, RHOU, INSM1, and RASSF10. Third, exosomal contents such as hsa-miR-21-5p promote distant bone formation of GHPA patients. Fourth, tumor suppressors in the exosome constitute novel therapeutic application of exosome, including long noncoding RNA (lncRNA) H19, miR-149-5p, miR-99a-3p, and miR-423-5p. This review discusses the possible mechanisms of exosome and their contents in PA and promotes the use of exosomes in both clinical diagnosis and treatment of this tumor.

The preparation of Escherichia coli competent cells by calcium chloride is a common method in molecular biology, but the mechanism is poorly understood. In a previous study, using transcriptomics and proteomics approaches, we found that the expression pattern of the gene loiP was upregulated by CaCl2. In order to investigate the function of the loiP gene in Ca2+- mediated formation of competent cells of E. coli DH5α, the loiP gene deletion strains were constructed by the lambda-derived Red homologous recombination technique. Then, the cell morphology, transformation efficiency, and cell membrane changes of the competent cells of the mutant strain were further explored. Compared with the wild-type E. coli DH5α, the mutant strains have no significant differences in the morphology, growth characteristics, and the permeability of the intracellular membrane. However, the transformation efficiencies of the mutant strains to plasmids of different sizes were significantly reduced, and the permeability of the outer membrane decreased by 2.94 times. These results indicate that the deletion of gene loiP may directly affect the transformation efficiency and outer membrane permeability of E. coli competent cells.

BackgroundBrain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined.MethodsThe cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate the cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data indicating a high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines.ResultsDifferences in macrophages and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and their biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital. We further evaluated the clinical significance of the BM-index and identified 7 drugs that potentially target BMAECs.ConclusionsThis study clarified possible cellular origins and drivers of metastatic LUAD at the single-cell level and laid a foundation for early detection of LUAD patients with a high risk of BM.

ObjectiveExcessive growth hormone and insulin-like growth factor 1 contribute to cutaneous changes in acromegaly. We investigated the sub-macroscopic skin manifestation of acromegaly patients and explored its reversibility upon hormone reduction after pituitary adenoma surgery.DesignProspectively cohort study.MethodsWe enrolled 26 patients with acromegaly and 26 patients with non-functioning pituitary adenomas undergoing pituitary adenomectomy at Peking Union Medical College Hospital from July 2021 to March 2022. Skin presentations were evaluated by dermatoscopy and ultra-high-frequency ultrasound before and after surgery.ResultsSkin thickening, follicular plugs, perifollicular pigmentations, perifollicular orange haloes, red structureless areas, increased hair shafts, honeycomb-like pigmentations, widened dermatoglyphics, dilated appendage openings, excessive seborrhea, hyperhidrosis, enlarged pores, and acne-like lesions were commonly occurring in acromegaly patients, and their incidences were higher than the controls (P1 skin lesions were younger (P=0.028) and had higher baseline GH levels (P=0.021) than those with improvement of ≤1 skin lesion.ConclusionsDermatoscopy and ultra-high-frequency ultrasound provided augmented visual examination of the cutaneous changes in acromegaly. Some of the skin lesions could improve or reverse after pituitary surgery. Baseline GH levels, age, and endocrine remission were correlated with skin improvement at 3-month follow-up.

Purpose: The diagnosis of glioma has got an advance since the WHO 2021 classification published with more molecular alternations involved in the integrate diagnoses pathways. Our study was aimed to show our experience on the clinical features and management of astrocytoma, IDH-mutant based on latest WHO classification. Methods: Patients diagnosed with astrocytoma, IDH-mutant based on WHO 5th edition classification of CNS tumors at our center from Jan 2009 to Jan 2022 were included, and divided to WHO 2-3 grade group and WHO 4 grade group. Integrate diagnoses according to WHO 2016 and 2021 classification were confirmed retrospectively. Clinical and MRI features were reviewed and survival analysis was done. Results: A total of 60 patients were included. 21.43% (6/28) of patients diagnosed with grade II and 58.33% (7/12) of patients with grade III by WHO 4th edition classification changed into grade 4 by WHO 5th classification. Sex, recurrent glioma and Ki-67 index of pathological exam were statistically different in WHO grade 2-3 group (n=27) and WHO grade 4 group (n=33). CDK6, FGFR2, MYC alterations shown an enrichment in WHO grade 4 group. Patients with higher grade shown shorter mOS (mOS=75.9m, 53.6m, 26.4m for grade 2, 3, 4 respectively). FGFR2 alternations was associated with worse survival for patients with astrocytoma, IDH-mutant, WHO grade 4 (p=0.013). Conclusion: Patients changed diagnoses as WHO grade 4 by 2021 WHO classification had worse prognoses, and treatment should be tailored personally for them. More researches of the management of IDH-mutant astrocytoma are needed in the future.

We aimed to explore the mechanism by how LX4211 affects bone marrow mesenchymal stem cells (BMSCs) during ischemia-reperfusion (I/R). BMSCs were extracted and treated with LX4211 followed by analysis of cell proliferation and migration by CCK-8, Transwell assay and wound healing tests, cell apoptosis and cycle by flow cytometry, exosomes and VEGFA secretion by immunoenzyme-linked adsorption. BMSCs treated with LX4211 or DMSO were administrated into mice with blood perfusion and capillary or arteriolar density was detected. Treatment with LX4211 significantly inhibited BMSCs proliferation, increased apoptosis and activated AMPK/ACC signaling along with reduced the number of exosomes and VEGFA level and impaired physiological functions. In vivo experiments determined that LX4211 alleviated I/R of lower limbs by inhibiting the muscle retention of BMSCs and paracrine. In conclusion, LX4211 treatment can delay the blood recovery of ischemic non-diabetic mice by reducing the proliferation, migration and impairing paracrine of BMSCs.

Tao Ouyang,1,&ast; Junxia Liu,2,&ast; Chengyang Shi,3 Lisheng Zhu,4 Xiaopeng Guo1 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao OuyangDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaTel +86 18720931226Email ouyt1996@163.comXiaopeng GuoDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, +86 13667216827Email guoxiaopenghe@163.comPurpose: This study aims to compare the efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus conventional TACE (cTACE), both combined with apatinib, and to establish predictive nomograms to support individualized survival prediction in hepatocellular carcinoma (HCC) patients.Patients and Methods: This retrospective study assessed HCC patients from June 2015 to December 2019. Patients were classified as DEB-TACE plus apatinib (D-apatinib) and cTACE plus apatinib (c-apatinib). The endpoints were overall survival (OS) and progression-free survival (PFS). The nomograms were constructed, and the C-index, receiver operating characteristic (ROC) curve, and calibration curves were used to validate the nomograms. Propensity score matching (PSM) analysis was applied to reduce patient selection bias.Results: A total of 174 patients were included. After PSM analysis, 58 pairs of patients were selected. Before PSM analysis, the median OS and PFS were 21.0 and 8.0 months in the D-apatinib group, respectively, which were better than the 18.0 and 5.0 months observed in the c-apatinib group (P < 0.05). The complete response (CR) rate and objective response rate (ORR) of the D-apatinib group were higher than those of the c-apatinib group. The C-index values of the nomograms in the D-apatinib group and the c-apatinib group were 0.826 and 0.802, and the area under the curve (AUC) values in the ROC curve were 0.934 and 0.892. After PSM analysis, the survival of patients treated with D-apatinib was better than that of patients treated with c-apatinib (P < 0.05). The C-index values were 0.854 and 0.794 in the D-apatinib group and the c-apatinib group, respectively, and the AUC values were 0.960 and 0.890. The incidence of adverse events was higher in the c-apatinib group.Conclusion: DEB-TACE in combination with apatinib showed better treatment effectiveness for unresectable HCC. The nomograms can identify HCC patients who may benefit most from the treatment.Keywords: hepatocellular carcinoma, DEB-TACE, cTACE, apatinib, nomogram, PSM

The purpose of this study was to evaluate the therapeutic efficacy and safety of endovascular treatment for patients with visceral and renal artery aneurysms (VRAAs). Twelve years of experience with interventional procedures and treatment options in our center were also worth discussing. From January 2009 to December 2020, clinical data of 159 consecutive patients with VRAAs were retrospectively analyzed. Patients' demographic and clinical data were recorded, and the safety and efficacy of endovascular therapy were evaluated. In addition, interventional procedures were also described. A total of 159 patients underwent angiography, and 154 patients were successfully treated with endovascular therapy, with a technical success rate of 96.9%. Of the 154 patients with successful endovascular therapy, 3 patients died within 30 days of treatment, with a 30-day mortality rate of 1.9%, and the remaining patients were clinically successful, with a clinical success rate of 98.1%. Fifty-seven patients underwent emergency interventional treatment due to ruptured aneurysm. There were statistically significant differences in hemoglobin before and after emergency treatment (78.5 ± 22.0 g/dL vs. 93.8 ± 15.0 g/dL, P = 0.00). No other serious complications occurred except death in 3 patients. Endovascular treatment of VRRAs is safe and effective and can significantly improve the symptoms of patients, especially those with ruptured aneurysms.

Pituitary adenoma is the second most common primary brain tumor. Perioperative hydrocortisone has been used for decades to avoid postoperative adrenal insufficiency. Recent studies suggest that withholding perioperative hydrocortisone may be safe for patients with an intact hypothalamus-pituitary-adrenal (HPA) axis.To assess the safety of withholding hydrocortisone during the perioperative period of pituitary adenoma surgery for patients with an intact HPA axis.A parallel-group, triple-masked, noninferiority randomized clinical trial was conducted at Peking Union Medical College Hospital from November 1, 2020, to January 31, 2022, among 436 patients aged 18 to 70 years with an intact HPA axis undergoing surgery for pituitary adenomas.Hydrocortisone supplementation protocol (intravenous and subsequent oral hydrocortisone, using a taper program) or no-hydrocortisone protocol.The primary outcome was the incidence of new-onset adrenal insufficiency (morning cortisol level,5 μg/dL with adrenal insufficiency-related symptoms) during the perioperative period (on the day of operation and the following 2 days). The secondary outcome was the incidence of adrenal insufficiency in postoperative month 3. Analysis was on an intention-to-treat basis.Of the 436 eligible patients, 218 were randomly assigned to the hydrocortisone group (136 women [62.4%]; mean [SD] age, 45.4 [13.0] years) and 218 to the no-hydrocortisone group (128 women [58.7%]; mean [SD] age, 44.5 [13.8] years). All patients completed 3-month postoperative follow-up. The incidence of new-onset adrenal insufficiency during the perioperative period was 11.0% (24 of 218; 95% CI, 6.9%-15.2%) in the no-hydrocortisone group and 6.4% (14 of 218; 95% CI, 3.2%-9.7%) in the hydrocortisone group, with a difference of 4.6% (95% CI, -0.7% to 9.9%), meeting the prespecified noninferiority margin of 10 percentage points. The incidence of adrenal insufficiency at the 3-month follow-up was 3.7% (8 of 218) in the no-hydrocortisone group and 3.2% (7 of 218) in the hydrocortisone group (difference, 0.5%; 95% CI, -3.0% to 3.9%). Incidences of new-onset diabetes mellitus (1 of 218 [0.5%] vs 9 of 218 [4.1%]), hypernatremia (9 of 218 [4.1%] vs 21 of 218 [9.6%]), hypokalemia (23 of 218 [10.6%] vs 34 of 218 [15.6%]), and hypocalcemia (6 of 218 [2.8%] vs 19 of 218 [8.7%]) were lower in the no-hydrocortisone group than in the hydrocortisone group. Lower preoperative morning cortisol levels were associated with higher risks of the primary event (9.3 µg/dL; odds ratio, 3.0; 95% CI, 1.5-5.9) and the secondary event (8.8 µg/dL; odds ratio, 7.8; 95% CI, 2.6-23.4) events.This study found that withholding hydrocortisone was safe and demonstrated noninferiority to the conventional hydrocortisone supplementation regimen regarding the incidence of new-onset adrenal insufficiency among patients with an intact HPA axis undergoing pituitary adenomectomy.ClinicalTrials.gov Identifier: NCT04621565.

To compare the difference in anterior segment biometrics derived from anterior segment optical coherence tomography (AS-OCT) between treatment-naïve acromegaly patients and normal controls and evaluate the correlations between above biometrics and insulin-like growth factor 1 (IGF-1) and growth hormone (GH) levels.Sixty eyes of 30 acromegaly patients and 60 eyes of 30 normal controls were included in this case-control study. Central corneal thickness, pupil diameter, iris thickness (IT), iris curvature (IC), anterior chamber depth (ACD), anterior chamber width, lens vault (LV), angle open distance (AOD) 500, AOD750, and trabecular iris space area (TISA) 500 and TISA750 were measured by AS-OCT. General linear regression models were constructed to evaluate the independent endocrine factors affecting iris morphology and anterior chamber angle (ACA) width.The acromegaly patients had an evenly thicker iris (Plt; 0.001), a smaller IC (Plt; 0.05), a smaller LV (P = 0.040) and significantly larger AOD500, AOD750, TISA500 and TISA750 (Plt; 0.001). There was a positive correlation between the serum GH level and ACD in the acromegaly patients (P = 0.031). Linear regression models showed the lower LV and smaller IC were independent influencing factors of the increase in the AOD500, AOD750, and TISA750 and nasal TISA500. Serum IGF-1 was an independent factor for the increase in pupil diameter (β = 0.002, P = 0.031) and both the average nasal (β = 6.781*10-5, P = 0.049) and temporal (β = 7.736*10-5, P = 0.045) IT values and for the decrease in temporal IC (βlt; 0.001, P = 0.037). GH was an independent factor for the increase in temporal AOD750 (β = 0.001, P = 0.030) and temporal TISA750 (β = 0.002, P = 0.016).Patients with acromegaly have a thicker IT, smaller IC, and lower LV with a wider ACA than normal controls. Serum GH is independently correlated with the temporal ACA width, whereas serum IGF-1 is independently correlated with IT, pupil diameter, and IC.

Nicotine is an ingredient of tobacco, and its exposure increases various cancer risks, including oral cancer. Previous studies have focused on its addictive properties, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process of nicotine promoting the occurrence and development of oral cancer through data mining and experimental verification.This study involved three parts. First, the key genes related to nicotine-related oral cancer were screened out through data mining; second, the expression and clinical significance of the key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways such as TNF and Apelin pathways; and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to Bleomycin and Docetaxel.This study revealed SERPINE1 as the key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.

To push forward the development of electric vehicles while improving the economy and environment of virtual power plants (VPPs), research on the optimization of VPP capacity considering electric vehicles is carried out. In this paper, based on this, this paper first analyzes the framework of the VPP with electric vehicles and models each unit of the VPP. Secondly, the typical scenarios of wind power, photovoltaic, electric vehicle charging and discharging, and load are formed by the Monte Carlo method to reduce the output deviation of each unit. Then, taking the maximization of the net income and clean energy consumption of the VPP as the objective function, the capacity optimal allocation model of the VPP considering multiobjective is constructed, and the conditional value-at-risk (CVaR) is introduced to represent the investment uncertainty faced by the VPP. Finally, a VPP in a certain area of Shanxi Province is used to analyze a calculation example and solve it with CPLEX. The results of the calculation example show that, on the one hand, reasonable selection of the optimal scale of EV connected to the VPP is able to improve the economy and environment of the VPP. On the other hand, the introduction of CVaR is available for the improvement of the scientific nature of VPP capacity allocation decisions.

Purpose Diagnostic statements for pituitary adenomas (PAs) are complex and unstandardized. We aimed to determine the most commonly used elements contained in the statements and their combination patterns and variations in real-world clinical practice, with the ultimate goal of promoting standardized diagnostic recording and establishing an efficient element extraction process. Methods Patient medical records from 2012 to 2020 that included PA among the first three diagnoses were included. After manually labeling the elements in the diagnostic texts, we obtained element types and training sets, according to which an information extraction model was constructed based on the word segmentation model “Jieba” to extract information contained in the remaining diagnostic texts. Results A total of 576 different diagnostic statements from 4010 texts of 3770 medical records were enrolled in the analysis. The first ten diagnostic elements related to PA were histopathology, tumor location, endocrine status, tumor size, invasiveness, recurrence, diagnostic confirmation, Knosp grade, residual tumor, and refractoriness. The automated extraction model achieved F1-scores that reached 100% for all ten elements in the second round and 97.3–100.0% in the test set consisting of an additional 532 diagnostic texts. Tumor location, endocrine status, histopathology, and tumor size were the most commonly used elements, and diagnoses composed of the above elements were the most frequent. Endocrine status had the greatest expression variability, followed by Knosp grade. Among all the terms, the percentage of loss of tumor size was among the highest (21%). Among statements where the principal diagnoses were PAs, 18.6% did not have information on tumor size, while for those with other diagnoses, this percentage rose to 48% (P Conclusion Standardization of the diagnostic statement for PAs is unsatisfactory in real-world clinical practice. This study could help standardize a structured pattern for PA diagnosis and establish a foundation for research-friendly, high-quality clinical information extraction.

Lymph node metastasis (LNM) is an important cause leading to recurrence and development of head and neck carcinoma (HNC), with the precise mechanisms unclear. Thus, we aimed to identify the key genes involved in LNM and further evaluate their expressions and roles.A cohort of HNC in the TCGA was analyzed. The study involved three phases (one screening and two validation phases). First, the differentially expressed genes regarding LNM were screened, from which a key gene was identified by a series of data mining approaches. Then, the expressions and roles of the key gene were validated in HNC through bioinformatics. Afterward, the expression of the key gene was detected by qPCR, western blot, and Immunohistochemistry based on a cell model and a tissue microarray. Further, colony formation and transwell migration and invasion assays were used to evaluate the roles of the key gene.SPP1 was overexpressed in HNC tissues and was identified as the key gene. Overexpression of SPP1 in HNC was correlated with advanced pathological stages and T-stage, as well as the presence of LNM, which predicted poor prognosis. The expression of SPP1 was closely associated with the infiltration of immune cells in HNC, especially M2 macrophages. Lab experiments confirmed that SPP1 silence in HNC cells resulted in weakened invasive and metastatic abilities.This study reveals that SPP1 may be a key gene associated with LNM in HNC, raising the possibility of SPP1 as a target for HNC prevention and treatment.

Tumor-treating fields (TTFields), a noninvasive and innovative therapeutic approach, has emerged as the fourth most effective treatment option for the management of glioblastomas (GBMs), the most deadly primary brain cancer. According to on recent milestone randomized trials and subsequent observational data, TTFields therapy leads to substantially prolonged patient survival and acceptable adverse events. Clinical trials are ongoing to further evaluate the safety and efficacy of TTFields in treating GBMs and its biological and radiological correlations. TTFields is administered by delivering low-intensity, intermediate-frequency, alternating electric fields to human GBM function through different mechanisms of action, including by disturbing cell mitosis, delaying DNA repair, enhancing autophagy, inhibiting cell metabolism and angiogenesis, and limiting cancer cell migration. The abilities of TTFields to strengthen intratumoral antitumor immunity, increase the permeability of the cell membrane and the blood–brain barrier, and disrupt DNA-damage-repair processes make it a promising therapy when combined with conventional treatment modalities. However, the overall acceptance of TTFields in real-world clinical practice is still low. Given that increasing studies on this promising topic have been published recently, we conducted this updated review on the past, present, and future of TTFields in GBMs.

This study aimed to develop a mapping function that links the acromegaly quality of life (AcroQoL) questionnaire to EQ-5D-5L to obtain a preference-based utility value to inform economic evaluation. A nationwide cross-sectional questionnaire survey among patients with acromegaly was conducted online in China during 17 December 2019 to 6 January 2020. The study sample was randomly divided into a training set and a validation set. Ordinary least squares (OLS), Tobit, beta-based mixture, and adjusted limited dependent variable mixture models were tested for development of the function in the training set. Total and subscale scores and individual items of AcroQoL were included as predictors in the models along with their squared terms and demographic and clinical characteristics, and selected by backward stepwise selection. The root mean square error, mean absolute error, Akaike’s information criterion, Bayesian information criterion and adjusted R-square were used to assess goodness of fit and predictive ability of the models. There were 424 adult patients with acromegaly eligible for this analysis. Average EQ-5D-5L index score and AcroQoL score for them was 0.82 (SD = 0.15) and 44.3 (SD = 22.9), respectively. A total of 60 candidate models were tested. Considering model simplicity and predictive ability in both training and validation set, the best model was the OLS model using scores of physical dimension and its square term as predictors. A validated mapping function was developed in this study for estimating EQ-5D scores using AcroQoL outcomes. Its external validity can be further tested in other population with Acromegaly.

This paper presents the results of laboratory scale plate load tests on transparent soils reinforced with biaxial polypropylene geogrids. The influence of reinforcement length and number of reinforcement layers on the load-settlement response of the reinforced soil foundation was assessed by varying the reinforcement length and the number of geogrid layers, each spaced at 25% of footing width. The deformations of the reinforcement layers and soil under strip loading were examined with the aid of laser transmitters (to illuminate the geogrid reinforcement) and digital camera. A two-dimensional finite difference program was used to study the fracture of geogrid under strip loading considering the geometry of the model tests. The bearing capacity and stiffness of the reinforced soil foundation has increased with the increase in the reinforcement length and number of reinforcement layers, but the increase is more prominent by increasing number of reinforcement layers. The results from the physical and numerical modelling on reinforced soil foundation reveal that fracture of geogrid could initiate in the bottom layer of reinforcement and progress to subsequent upper layers. The displacement and stress contours along with the mobilized tensile force distribution obtained from the numerical simulations have complimented the observations made from the experiments.

Butanol inhibits bacterial activity by destroying the cell membrane of Clostridium acetobutylicum strains and altering functionality. Butanol toxicity also results in destruction of the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS), thereby preventing glucose transport and phosphorylation and inhibiting transmembrane transport and assimilation of sugars, amino acids, and other nutrients. In this study, based on the addition of exogenous butanol, the tangible macro indicators of changes in the carbon ion beam irradiation-mutant Y217 morphology were observed using scanning electron microscopy (SEM). The mutant has lower microbial adhesion to hydrocarbon (MATH) value than C. acetobutylicum ATCC 824 strain. FDA fluorescence intensity and conductivity studies demonstrated the intrinsically low membrane permeability of the mutant membrane, with membrane potential remaining relatively stable. Monounsaturated FAs (MUFAs) accounted for 35.17% of the mutant membrane, and the saturated fatty acids (SFA)/unsaturated fatty acids (UFA) ratio in the mutant cell membrane was 1.65. In addition, we conducted DNA-level analysis of the mutant strain Y217. Expectedly, through screening, we found gene mutant sites encoding membrane-related functions in the mutant, including ATP-binding cassette (ABC) transporter-related genes, predicted membrane proteins, and the PTS transport system. It is noteworthy that an unreported predicted membrane protein (CAC 3309) may be related to changes in mutant cell membrane properties. KEY POINTS: • Mutant Y217 exhibited better membrane integrity and permeability. • Mutant Y217 was more resistant to butanol toxicity. • Some membrane-related genes of mutant Y217 were mutated.

Background Facial abnormality is the most significant feature in acromegaly patients. However, it is unclear whether and how patient facial appearance improves after treatment. This study aimed to identify 3D facial changes in acromegaly patients after surgical treatment. Methods This study included 30 acromegaly patients who underwent resection of a pituitary GH adenoma. The location and extent of facial changes were identified by comparing baseline and 2-year follow-up 3D images of the face. Relationships between facial changes and GH and IGF-1 were evaluated with simple or multivariable linear regression models. Results Significant soft tissue improvements were observed in acromegaly patients with complete remission, especially in the nose and lip region. Significant reductions in nasal width (3.46 mm, P < 0.001), tip protrusion (1.18 mm, P = 0.003), face curve length (3.89 mm, P = 0.004) and vermilion area (1.42 cm3, P = 0.001) were observed at the 2-year follow-up. Further, changes in nasal width were associated with decreases in GH (β = 4.440, P = 0.017), the GH nadir (β = 4.393, P = 0.011) and IGF-1 (β = 5.263, P = 0.002). The associations were maintained after adjusting for confounders. Conclusions Acromegaly patients achieved considerable facial improvements after surgical treatment. The change in nose width was associated with GH and IGF-1 decrease. Better control of patient hormone levels after surgery improves patient facial recovery.

Tumor resection is the first-line therapy for acromegaly patients. In some cases, unsatisfactory intraoperative neuromuscular blockades (NMBs) lead to failed operations. The purpose of this study was to investigate and quantify the NMB status of acromegaly patients and explore the relationship between NMB status and hormone levels and body composition. Twenty patients with untreated acromegaly and seventeen patients with nonfunctioning pituitary adenomas as controls were enrolled in this study. NMB was assessed using the train-of-four (TOF) technique with TOF-Watch® SX. The onset time of NMB, deep neuromuscular blockade duration (DNMBD), and clinical neuromuscular blockade duration (CNMBD) were monitored. We found a significantly longer onset time (110.25 ± 54.90 vs. 75.00 ± 27.56, s, p = 0.017 ), shorter DNMBD (21.99 ± 5.67 vs. 34.96 ± 11.04, min, p < 0.001 ), and shorter CNMBD (33.26 ± 8.09 vs. 46.21 ± 10.89, min, p < 0.001 ) in acromegaly patients compared with the controls. DNMBD and CNMBD decreased in patients with decreasing body fat percentage and increasing growth hormone (GH) level, insulin-like growth factor 1 (IGF-1) level, and GH and IGF-1 burden. The onset time increased with increasing IGF-1 level and GH and IGF-1 burden. Taken together, a unique NMB status was identified in acromegaly patients with the following characteristics: prolonged onset time and shortened DNMBD and CNMBD. Changes in the levels and burdens of GH and IGF-1 and body composition were linearly correlated with intraoperative NMB in acromegaly patients.