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Hepatocellular carcinoma (HCC) is one of the primary forms of liver cancer and is currently the sixth most prevalent malignancy worldwide. In addition to surgical interventions, effective drug treatment is essential for treating HCC. With an increasing number of therapeutic drugs for liver cancer undergoing clinical studies, the therapeutic strategies for advanced HCC are more diverse than ever, leading to improved prospects for HCC patients. Molecular targeted drugs and immunotherapies have become crucial treatment options for HCC. Treatment programs include single-agent molecular-targeted drugs, immunotherapies, combinations of immunotherapies with molecular-targeted drugs, and dual immune checkpoint inhibitors. However, further exploration is necessary to determine the optimal pharmacological treatment regimens, and the development of new effective drugs is urgently needed. This review provides an overview of the current globally approved drugs for liver cancer, as well as the latest advances in ongoing clinical research and drug therapies. Additionally, the review offers an outlook and discussion on the prospects for the development of drug therapy approaches for HCC.

BackgroundLipofibromatosis-like neural tumors (LPF-NT), which have only recently been established, are intermediate soft tissue tumors with neurotrophic tropomyosin receptor kinase 1 (NTRK1) gene alterations and are typically misdiagnosed as dermatofibrosarcoma protuberans, low-grade malignant peripheral nerve sheath tumors, or spindle cell lipoma due to their histopathological and immunohistochemical expression of CD34 and S-100.Case presentationThe patient was admitted to our hospital with a painless back mass that had appeared more than 4 years prior to admission. Physical examination revealed a subcutaneous mass on the back, approximately 1.5 cm in diameter and protruding into the skin, with clear boundaries and no tenderness. The tumor was surgically resected. The postoperative pathological results suggested a spindle cell soft tissue tumor, and dermatofibrosarcoma protuberan was initially considered. After consultation at a provincial hospital, the patient was diagnosed with a cutaneous lipofibromatosis-like neural tumor of the back. A second extended resection was then performed. Intraoperative rapid freezing examination revealed negative incision margins.ConclusionHistological and immunohistochemical detections aid in the differential diagnosis of LPF-NTs. Complete surgical resection is the preferred treatment for LPF-NTs.

IntroductionSpecialized care is essential for the recovery of children with cerebral palsy (CP). This study investigates how different care modes impact the gut microbiota.MethodsFecal samples from 32 children were collected, among whom those cared for by family (n = 21) were selected as the observation group, and those cared for by children's welfare institutions (n = 11) were selected as the control group (registration number of LGFYYXLL-024). The gut microbiota profiles were analyzed.ResultsThere was no significant difference in the α-diversity of the gut microbiota and the abundance at the phylum level. However, at the genus level, the observation group showed a significant increase in the abundance of butyrate-producing bacteria Bacteroides and Lachnospiracea incertae sedis (P

BackgroundSolitary fibrous tumors are rare mesenchymal tumors that typically occur in the pleura. Solitary fibrous tumors of the uterine cervix are uncommon. We report the first case of a patient who underwent total hysterectomy for vaginal wall adenocarcinoma and was found to have a concurrent solitary fibrous tumor in the paracervical-uterus.Case presentationA 51-year-old woman was admitted to our hospital due to contact bleeding. A gynecological examination revealed nodules of 3.0 × 1.0 cm on the vaginal wall, and a colposcopy with biopsy revealed adenocarcinoma of the vaginal wall. After the recommended staging examinations, the patient underwent total hysterectomy, double adnexectomy, pelvic lymph node dissection, and vaginal wall resection. During surgery, a nodule measuring approximately 2 × 2 cm was found in the middle of the mass in the left paracervical region. Subsequent postoperative histopathological examination confirmed an solitary fibrous tumor of the uterine cervix with adenocarcinoma of the vaginal wall. The patient was followed up for 46 months after hospitalization, and no recurrence or distant metastases were observed.ConclusionIn rare cases, solitary fibrous tumors may form large masses in the cervical or vaginal wall. They can easily be misdiagnosed as benign or malignant cervical tumors before and during surgery. Postoperative pathology and immunohistochemistry are helpful for diagnosis. Most solitary fibrous cervical tumors are benign, occasionally with low malignant potential, and surgical treatment is feasible and effective.

With the continuous construction of high-voltage direct-current (HVDC) transmission projects, higher requirements are placed on the frequency security of the regional power systems. In order to ensure the frequency security of regional power systems, this paper proposes a transient frequency analytical method considering the emergency frequency control (EFC). Firstly, the aggregated system frequency response (SFR) model is constructed by reducing the order of the generator governor equation, the EFC equation, and the load model equation. Then, based on the aggregation model, the analytical solution of the transient frequency nadir of the regional power system is derived. The model can quickly and accurately calculate the transient frequency nadir of the regional power system considering EFC after the HVDC block fault. Finally, based on an actual regional power system model, the accuracy and applicability of the proposed method under HVDC block fault are verified.

Clubroot disease poses a significant threat to Brassica crops, necessitating ongoing updates on resistance gene sources. In F2 segregants of the clubroot-resistant inbred line BrT18-6-4-3 and susceptible DH line Y510, the genetic analysis identified a single dominant gene responsible for clubroot resistance. Through bulk segregant sequencing analysis and kompetitive allele-specific polymerase chain reaction assays, CRA8.1.6 was mapped within 110 kb (12,255–12,365 Mb) between markers L-CR11 and L-CR12 on chromosome A08. We identified B raA08g015220.3.5C as the candidate gene of CRA8.1.6. Upon comparison with the sequence of disease-resistant material BrT18-6-4-3, we found 249 single-nucleotide polymorphisms, seven insertions, six deletions, and a long terminal repeat (LTR) retrotransposon (5,310 bp) at 909 bp of the first intron. However, the LTR retrotransposon was absent in the coding sequence of the susceptible DH line Y510. Given the presence of a non-functional LTR insertion in other materials, it showed that the LTR insertion might not be associated with susceptibility. Sequence alignment analysis revealed that the fourth exon of the susceptible line harbored two deletions and an insertion, resulting in a frameshift mutation at 8,551 bp, leading to translation termination at the leucine-rich repeat domain’s C-terminal in susceptible material. Sequence alignment of the CDS revealed a 99.4% similarity to Crr1a, which indicate that CRA8.1.6 is likely an allele of the Crr1a gene. Two functional markers, CRA08-InDel and CRA08-KASP1, have been developed for marker-assisted selection in CR turnip cultivars. Our findings could facilitate the development of clubroot-resistance turnip cultivars through marker-assisted selection.

Primary myxofibrosarcoma of the heart, a rare cardiac malignancy, was diagnosed in a middle-aged female patient exhibiting progressive dyspnea following transthoracic echocardiography and pathological analysis. Postoperatively, the patient underwent chemotherapy and Lenvatinib mesylate therapy, with regular check-ups confirming her survival. After 10 months the patient is still alive and well.

Valorization of food processing effluent (FPE) by microalgae cultivation for astaxanthin production is regarded as a potential strategy to solve the environmental pollution of food processing industry and promote the development of eco-friendly agriculture. In this review paper, microalgal species which have the potential to be employed for astaxanthin in FPE were identified. Additionally, in terms of CO2 emission, the performances of microalgae cultivation and traditional methods for FPE remediation were compared. Thirdly, an in-depth discussion of some innovative technologies, which may be employed to lower the total cost, improve the nutrient profile of FPE, and enhance the astaxanthin synthesis, was provided. Finally, specific effects of dietary supplementation of algal astaxanthin on the growth rate, immune response, and pigmentation of animals were discussed. Based on the discussion of this work, the cultivation of microalgae in FPE for astaxanthin production is a value-adding process which can bring environmental benefits and ecological benefits to the food processing industry and agriculture. Particularly, technological innovations in recent years are promoting the shift of this new idea from academic research to practical application. In the coming future, with the reduction of the total cost of algal astaxanthin, policy support from the governments, and further improvement of the innovative technologies, the concept of growing microalgae in FPE for astaxanthin will be more applicable in the industry.

Droop control is widely used in multi-terminal flexible DC (VSC-MTDC) transmission systems by virtue of the advantage of multi-station cooperative unbalanced power dissipation, however, the essence of the droop control strategy is to change the DC current to realize the unbalanced power dissipation, and the resulting DC voltage deviation will affect the normal operation of the system. Firstly, this paper theoretically analyses the working characteristics of the conventional droop control and proposes a control method to realize the quasi-differential-free regulation of DC voltage by translating the droop curve. Second, according to the power margin of the converter station, the feedforward compensation amount of each converter station is reasonably set to avoid the power impact on the converter station. Finally, for the problem that the actual value of DC voltage still deviates from the rated value, a control strategy containing secondary regulation of DC voltage is proposed to further restore the DC voltage to the initial value on the basis of ensuring the effect of power regulation, which improves the stability of the operation of the VSC-MTDC system. The final simulation results verify the effectiveness of the proposed method.

BackgroundThe novel International Association for the Study of Lung Cancer (IASLC) grading system suggests that poorly differentiated invasive pulmonary adenocarcinoma (IPA) has a worse prognosis. Therefore, prediction of poorly differentiated IPA before treatment can provide an essential reference for therapeutic modality and personalized follow-up strategy. This study intended to train a nomogram based on CT intratumoral and peritumoral radiomics features combined with clinical semantic features, which predicted poorly differentiated IPA and was tested in independent data cohorts regarding models’ generalization ability.MethodsWe retrospectively recruited 480 patients with IPA appearing as subsolid or solid lesions, confirmed by surgical pathology from two medical centers and collected their CT images and clinical information. Patients from the first center (n =363) were randomly assigned to the development cohort (n = 254) and internal testing cohort (n = 109) in a 7:3 ratio; patients (n = 117) from the second center served as the external testing cohort. Feature selection was performed by univariate analysis, multivariate analysis, Spearman correlation analysis, minimum redundancy maximum relevance, and least absolute shrinkage and selection operator. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the model performance.ResultsThe AUCs of the combined model based on intratumoral and peritumoral radiomics signatures in internal testing cohort and external testing cohort were 0.906 and 0.886, respectively. The AUCs of the nomogram that integrated clinical semantic features and combined radiomics signatures in internal testing cohort and external testing cohort were 0.921 and 0.887, respectively. The Delong test showed that the AUCs of the nomogram were significantly higher than that of the clinical semantic model in both the internal testing cohort(0.921 vs 0.789, p< 0.05) and external testing cohort(0.887 vs 0.829, p< 0.05).ConclusionThe nomogram based on CT intratumoral and peritumoral radiomics signatures with clinical semantic features has the potential to predict poorly differentiated IPA manifesting as subsolid or solid lesions preoperatively.

In order to study the effects of stress change and adaptability of the overrun hydraulic stent under impact load, the rigid–flexible coupling numerical model of the stent is established using multi-body dynamics simulation software ADAMS. In the model, the stent is flexibilized using the HyperMesh module, and the column and jack are equivalently replaced with a spring damping system. By applying impact loads to different positions above the front roof beam of the stent, the dynamic response characteristics of the column and the articulation point are obtained at different positions with different strengths. The results show that when the impact load is applied to different positions of the front roof beam, the steady-state response force of the column shows an overall “M" distribution, and along the length direction of the roof beam, the steady-state response force of the column shows an upward trend, and the maximum steady-state response force of the column is 547 kN at point (1, 6); when the impact load is applied to both sides of the front roof beam, the response at the articulation point is greater, resulting in a higher maximum simple harmonic response at that articulation point. When the impact load acts on both sides of the front roof beam, the response of the articulation point is greater, with a maximum simple harmonic response coefficient of 0.75 and a maximum excitation response coefficient of 0.28; when the impact loads of different strengths act on the whole front roof beam, the force acting on the column and pin shaft at the articulation point will produce a large impact, reducing its adaptability. To address this, we can consider changing the top plate stress conditions using methods like high-pressure injection of water and control the gradual and slow release of the top plate stresses. The results of the study provide a reference for the structural strength design and reliability analysis of the hydraulic support, which is of practical significance and value for improving the safe mining of the coal mining face.

IntroductionThe design of high-pressure optical windows is one of the key tasks in deep-sea exploration, as it directly determines the reliability and maximum operating depth of underwater optical equipment.MethodIn this paper, mechanical modeling and finite element analysis methods are employed to study optical windows.Results and discussionResults show that changes in boundary conditions during loading significantly affect the stress distribution of the window. Based on this conclusion, an optimization design method is proposed, which involves the use of transition materials to reduce the impact of base deformation on the window. The study further analyzes the effects of the transition material’s Young’s modulus, Poisson’s ratio, thickness, and friction coefficient on the stress of the optical window. A calculation method for material selection criteria is proposed to select appropriate transition materials, and actual materials are used for verification. Finally, the reliability of the optimization design scheme based on transition materials is confirmed through high-pressure experiments.

Background and objectives: The heterogeneity of pulmonary fibroblasts, a critical aspect of both murine and human models under physiological and pathological conditions, is well-documented. Yet, consensus remains elusive on the subtypes, lineage, biological attributes, signal transduction pathways, and plasticity of these fibroblasts. This ambiguity significantly impedes our understanding of the fibrotic processes that transpire in lung tissue during aging. This study aims to elucidate the transcriptional profiles, differentiation pathways, and potential roles of fibroblasts within aging pulmonary tissue.Methods: We employed single-cell transcriptomic sequencing via the 10x Genomics platform. The downstream data were processed and analyzed using R packages, including Seurat. Trajectory and stemness of differentiation analyses were conducted using the Monocle2 and CytoTRACE R packages, respectively. Cell interactions were deciphered using the CellChat R package, and the formation of collagen and muscle fibers was identified through Masson and Van Geison staining techniques.Results: Our analysis captured a total of 22,826 cells, leading to the identification of fibroblasts and various immune cells. We observed a shift in fibroblasts from lipogenic and immune-competent to fibrotic and myofibroblast-like phenotype during the aging process. In the aged stage, fibroblasts exhibited a diminished capacity to express chemokines for immune cells. Experimental validation confirmed an increase of collagen and muscle fiber in the aged compared to young lung tissues. Furthermore, we showed that TGFβ treatment induced a fibrotic, immunodeficient and lipodystrophic transcriptional phenotype in young pulmonary fibroblasts.Conclusion: We present a comprehensive single-cell transcriptomic landscape of lung tissue from aging mice at various stages, revealing the differentiation trajectory of fibroblasts during aging. Our findings underscore the pivotal role of fibroblasts in the regulation of immune cells, and provide insights into why age increases the risk of pulmonary fibrosis.

BackgroundFunctional restoration of hemiplegic upper limbs is a difficult area in the field of neurological rehabilitation. Electrical stimulation is one of the treatments that has shown promising advancements and functional improvements. Most of the electrical stimulations used in clinical practice are surface stimulations. In this case, we aimed to investigate the feasibility of a minimally invasive, ultrasound-guided median nerve electrical stimulation (UG-MNES) in improving the upper limb motor function and activity of a patient with right-sided hemiparesis.Case presentationA 65-year-old male recovering from a left massive intracerebral hemorrhage after open debridement hematoma removal had impaired right limb movement, right hemianesthesia, motor aphasia, dysphagia, and complete dependence on his daily living ability. After receiving 3 months of conventional rehabilitation therapy, his cognitive, speech, and swallowing significantly improved but the Brunnstrom Motor Staging (BMS) of his right upper limb and hand was at stage I-I. UG-MNES was applied on the right upper limb for four sessions, once per week, together with conventional rehabilitation. Immediate improvement in the upper limb function was observed after the first treatment. To determine the effect of UG-MNES on long-term functional recovery, assessments were conducted a week after the second and fourth intervention sessions, and motor function recovery was observed after 4-week of rehabilitation. After completing the full rehabilitation course, his BMS was at stage V-IV, the completion time of Jebsen Hand Function Test (JHFT) was shortened, and the scores of Fugl-Meyer Assessment for upper extremity (FMA-UE) and Modified Barthel Index (MBI) were increased. Overall, the motor function of the hemiplegic upper limb had significantly improved, and the right hand was the utility hand. Electromyography (EMG) and nerve conduction velocity (NCV) tests were normal before and after treatment.ConclusionThe minimally invasive, UG-MNES could be a new alternative treatment in stroke rehabilitation for functional recovery of the upper limbs.

This paper investigates the selection of voxels for functional Magnetic Resonance Imaging (fMRI) brain data. We aim to identify a comprehensive set of discriminative voxels associated with human learning when exposed to a neutral visual stimulus that predicts an aversive outcome. However, due to the nature of the unconditioned stimuli (typically a noxious stimulus), it is challenging to obtain sufficient sample sizes for psychological experiments, given the tolerability of the subjects and ethical considerations. We propose a stable hierarchical voting (SHV) mechanism based on stability selection to address this challenge. This mechanism enables us to evaluate the quality of spatial random sampling and minimizes the risk of false and missed detections. We assess the performance of the proposed algorithm using simulated and publicly available datasets. The experiments demonstrate that the regularization strategy choice significantly affects the results' interpretability. When applying our algorithm to our collected fMRI dataset, it successfully identifies sparse and closely related patterns across subjects and displays stable weight maps for three experimental phases under the fear conditioning paradigm. These findings strongly support the causal role of aversive conditioning in altering visual-cortical activity.

Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.

BackgroundTransmembrane (TMEM) protein genes are a class of proteins that spans membranes and function to many physiological processes. However, there is very little known about TMEM gene expression, especially in cancer tissue. Using single-cell and bulk RNA sequence may facilitate the understanding of this poorly characterized protein genes in PDAC.MethodsWe selected the TMEM family genes through the Human Protein Atlas and characterized their expression by single-cell and bulk transcriptomic datasets. Identification of the key TMEM genes was performed through three machine learning algorithms: LASSO, SVM-RFE and RF-SRC. Then, we established TMEM gene riskscore and estimate its implication in predicting survival and response to systematic therapy. Additionally, we explored the difference and impact of TMEM gene expression in PDAC through immunohistochemistry and cell line research.Results5 key TMEM genes (ANO1, TMEM59, TMEM204, TMEM205, TMEM92) were selected based on the single-cell analysis and machine learning survival outcomes. Patients stratified into the high and low-risk groups based on TMEM riskscore, were observed with distinct overall survival in internal and external datasets. Moreover, through bulk RNA-sequence and immunohistochemical staining we verified the protein expression of TMEM genes in PDAC and revealed TMEM92 as an essential regulator of pancreatic cancer cell proliferation, migration, and invasion.ConclusionOur study on TMEM gene expression and behavior in PDAC has revealed unique characteristics, offering potential for precise therapeutic approaches. Insights into molecular mechanisms expand understanding of PDAC complexity and TMEM gene roles. Such knowledge may inform targeted therapy development, benefiting patients.

Maternal sepsis is a life-threatening condition and ranks among the top five causes of maternal death in pregnancy and the postpartum period. Herein, we conducted a retrospective study on sepsis cases to explain the related risk factors by comparing them with bloodstream infection (BSI) and control maternities. In total, 76 sepsis cases were enrolled, and 31 BSI and 57 maternal cases of the same age but with neither sepsis nor BSI were set as controls. Genital tract infection (GTI) and pneumonia were the two most common infection sources in both sepsis (22 cases, 29% and 29 cases, 38%) and BSI cases (18 cases, 58% and 8 cases, 26%). Urinary tract infection (UTI)/pyelonephritis (9 cases, 12%) and digestive infection cases (11 cases, 14%) only existed in the sepsis group. Significantly different infection sources were discovered between the sepsis-death and sepsis-cure groups. A higher proportion of pneumonia and a lower proportion of GTI cases were present in the sepsis-death group (17 cases, 45% pneumonia and 9 cases, 24% GTI) than in the sepsis-cure group (12 cases, 32% pneumonia and 13 cases, 34% GTI). In addition, although gram-negative bacteria were the dominant infectious microorganisms as previously reported, lower proportion of gram-negative bacteria infectious cases in sepsis (30 cases, 50%) and even lower in sepsis-death group (14 cases, 41%) was shown in this study than previous studies. As expected, significantly greater adverse maternal and fetal outcomes, such as higher maternal mortality (26.3% vs. 0% vs. 0%), higher fetal mortality (42.2% vs. 20.8% vs. 0%), earlier gestational age at delivery (26.4 ± 9.5 vs. 32.3 ± 8.1 vs. 37.7 ± 4.0) and lower newborn weight (1,590 ± 1287.8 vs. 2859.2 ± 966.0 vs. 3214.2 ± 506.4), were observed in the sepsis group. This study offered some potential pathogenesis and mortality risk factors for sepsis, which may inspire the treatment of sepsis in the future.

BackgroundThis study aims to investigate the risk factors for in-hospital death in patients with acute aortic dissection (AAD) and to provide a straightforward prediction model to assist clinicians in determining the outcome of AAD patients.MethodsRetrospective analysis was carried out on 2,179 patients admitted for AAD from March 5, 1999 to April 20, 2018 in Wuhan Union Hospital, China. The risk factors were investigated with univariate and multivariable logistic regression analysis.ResultsThe patients were divided into two groups: Group A, 953patients (43.7%) with type A AAD; Group B, 1,226 patients (56.3%) with type B AAD. The overall in-hospital mortality rate was 20.3% (194/953) and 4% (50/1,226) in Group A and B respectively. The multivariable analysis included the variables that were statistically significant predictors of in-hospital death (P

IntroductionA superficial cervical vaginal myofibroblastoma is a rare mesenchymal tumor, originating from the superficial stroma of the vagina and cervix. This study reports a patient, who was diagnosed with endometrioid carcinoma and a concomitant benign superficial cervicovaginal myofibroblastoma.Case presentationA 53-year-old female with endometrial carcinoma was admitted to the Department of Gynecology of our hospital. She had a history of breast cancer on May 23, 2010, and took toremifene citrate for 41 months. Radical resection of the endometrial carcinoma was performed at our hospital. Based on the pathological findings, she was postoperatively diagnosed with endometrial adenocarcinoma with superficial cervical vaginal myofibroblastoma. The patient continued receiving postoperative breast cancer treatment. She underwent follow-up for 23 months. No recurrence or metastasis of the endometrial cancer or superficial cervical vaginal myofibroblastoma was observed.ConclusionThere were similarities between superficial cervical vaginal myofibroblastoma and other mesenchymal tumors of the female genital tract. Superficial cervical vaginal myofibroblastomas have a good prognosis, and the combination of tissue morphology and immunohistochemistry helped establish a definitive diagnosis.

SignificanceCardiovascular diseases are seen to be a primary cause of death, and their prevalence has significantly increased across the globe in the past few years. Several studies have shown that cell death is closely linked to the pathogenesis of cardiovascular diseases. Furthermore, many molecular and cellular mechanisms are involved in the pathogenesis of the cardiac cell death mechanism. One of the factors that played a vital role in the pathogenesis of cardiac cell death mechanisms included the early growth response-1 (Egr-1) factor.Recent AdvancesStudies have shown that abnormal Egr-1 expression is linked to different animal and human disorders like heart failure and myocardial infarction. The biosynthesis of Egr-1 regulates its activity. Egr-1 can be triggered by many factors such as serum, cytokines, hormones, growth factors, endotoxins, mechanical injury, hypoxia, and shear stress. It also displays a pro-apoptotic effect on cardiac cells, under varying stress conditions. EGR1 mediates a broad range of biological responses to oxidative stress and cell death by combining the acute changes occurring in the cellular environment with sustained changes in gene expression.Future DirectionsThe primary regulatory role played by the Egr-1-targeting DNAzymes, microRNAs, and oligonucleotide decoy strategies in cardiovascular diseases were identified to provide a reference to identify novel therapeutic targets for cardiovascular diseases.

Introduction: Aiming at the problem of structural damage of top beam and column in the actual bearing process of top coal caving hydraulic support caused by uneven roof pressure in the process of fully mechanized caving mining in thick coal seam coal mine, this paper analyzes the dynamic bearing performance of ZF20000/26/48 top coal caving hydraulic support based on the working conditions given by the 101 working face of Shaanxi Zheng-tong Coal Mine.Methods: Genetic algorithm was used to optimize the top beam of hydraulic support.Results: Under the same loading conditions, the maximum stress of the optimized support is reduced by 22.28MPa, and the stress of the top beam is more uniform, and the maximum stress is reduced by 24.53MPa.Discussion: The purpose of optimization design is achieved, and the bearing performance of hydraulic support is improved,A new method using genetic algorithm to optimize the top beam of hydraulic support is developed.

BackgroundAn inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor with a prevalence ranging from 0.04% to 0.7% worldwide, in which the lung is the most common predilection site, accounting for 33% of cases, followed by the abdomen, pelvis, mesentery, and uterus. Approximately 50% of uterine IMTs present as anaplastic lymphoma kinase (ALK) positive along with ALK gene fusion, which lays a solid foundation for the development of ALK-based target therapy to optimize treatment strategies.Case presentationHerein we describe a 57-year-old woman who presented with a slow-growing mass in the uterus for over 10 years and then received surgical resection because of significant progressive enlargement of the mass during follow-up. She was diagnosed with uterine leiomyosarcoma (LMS) with no further interventions until recurrence. We revised the diagnosis to uterine IMT based on diffuse ALK expression, ALK-IGFBP5 gene fusion, and the morphologic features of the tumors by pathology consultation. Based on these, we recommended an ALK tyrosine kinase inhibitor (TKI) treatment, crizotinib (250 mg bid), and she achieved a complete response (CR) with at least 18 months of progression-free survival (PFS). We monitored the dynamics of target lesions and peripheral blood cells at regular intervals through CT scans and routine blood tests during the treatment process. We present patient responses to ALK inhibitor-based targeted therapy with uterine IMT harboring ALK-IGFBP5 fusion, and the neutrophil-to-lymphocyte ratio (NLR) may be an effective indicator to predict prognosis.

BackgroundEmerging evidence indicates that air pollutants contribute to the development and progression of gastrointestinal diseases. However, there is scarce evidence of an association with appendicitis in mainland China.MethodsIn this study, Linfen city, one of the most polluted cities in mainland China, was selected as the study site to explore whether air pollutants could affect appendicitis admissions and to identify susceptible populations. Daily data on appendicitis admissions and three principal air pollutants, including inhalable particulate matter (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were collected in Linfen, China. The impacts of air pollutants on appendicitis were studied by using a generalized additive model (GAM) combined with the quasi-Poisson function. Stratified analyses were also performed by sex, age, and season.ResultsWe observed a positive association between air pollution and appendicitis admissions. For a 10 μg/m3 increase in pollutants at lag01, the corresponding relative risks (RRs) and 95% confidence intervals (95% CIs) were 1.0179 (1.0129–1.0230) for PM10, 1.0236 (1.0184–1.0288) for SO2, and 1.0979 (1.0704–1.1262) for NO2. Males and people aged 21–39 years were more susceptible to air pollutants. Regarding seasons, the effects seemed to be stronger during the cold season, but there was no statistically significant difference between the seasonal groups.ConclusionsOur findings indicated that short-term air pollution exposure was significantly correlated with appendicitis admissions, and active air pollution interventions should be implemented to reduce appendicitis hospitalizations, especially for males and people aged 21–39 years.

To examine the development of visual aesthetic sensitivity in students in China, 2,387 students from age 9 to age 22 (excluding ages 16–17) were tested by the Visual aesthetic Sensitivity Test-Revised. The development of visual aesthetic sensitivity across ages and genders, and the effect of artistic training on students’ visual aesthetic sensitivity were examined. The data of primary school and junior middle school students were collected by paper tests completed collectively in class, while the data of university students were collected by distributing and collecting online. Result suggests that students’ visual aesthetic sensitivity is relatively stable from age 9 to age 12 and increases at age 13. The visual aesthetic sensitivity of girls is significantly better than that of boys at age 15, 19, and 20 years of age. This study also found that artistic training improves students’ visual aesthetic sensitivity.

Introduction: In this study, Poly (trimethylene carbonate)/Doxycycline hydrochloride (PTMC/DH) films were introduced to repair the Achilles tendon defects for the first time.Methods: (PTMC/DH) films with different DH content of 10, 20, and 30% (w/w) were prepared by solvent casting. The in vitro and in vivo drug release of the prepared PTMC/DH films was investigated.Results: The results of drug release experiments showed that the PTMC/DH films released effective concentrations of doxycycline for more than 7 and 28 days in vitro and in vivo, respectively. The results of antibacterial activity experiments showed diameters of 25.00 ± 1.00 mm, 29.33 ± 1.15 mm, and 34.67 ± 1.53 mm, respectively, for the inhibition zones produced by the release solutions of PTMC/DH films with 10, 20 and 30% (w/w) DH at 2 h, indicating that the drug-loaded films could inhibit Staphylococcus aureus well. After treatment, the Achilles tendon defects have recovered well, as indicated by the more robust biomechanical properties and the lower fibroblast density of the repaired Achilles tendons. Pathology revealed that the pro-inflammatory cytokine, IL-1β, and the anti-inflammatory factor, TGF-β1, peaked in the first three days and gradually decreased as the drug was released more slowly.Discussion: These results demonstrated that the PTMC/DH films have great potential for regenerating Achilles tendon defects.

PurposeUbiquitin-conjugating enzymes E2S (UBE2S) and E2C (UBE2C), which mediate the biological process of ubiquitination, have been widely reported in various cancers. Numb, the cell fate determinant and tumor suppressor, was also involved in ubiquitination and proteasomal degradation. However, the interaction between UBE2S/UBE2C and Numb and their roles in the clinical outcome of breast cancer (BC) are not widely elucidated.MethodsOncomine, Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) database, qRT-PCR, and Western blot analyses were utilized to analyze UBE2S/UBE2C and Numb expression in various cancer types and their respective normal controls, breast cancer tissues, and breast cancer cell lines. The expression of UBE2S, UBE2C, and Numb in BC patients with different ER, PR, and HER2 status, grades, stages, and survival status was compared. By Kaplan–Meier plotter, we further evaluated the prognostic value of UBE2S, UBE2C, and Numb in BC patients. We also explored the potential regulatory mechanisms underlying UBE2S/UBE2C and Numb through overexpression and knockdown experiments in BC cell lines and performed growth and colony formation assays to assess cell malignancy.ResultsIn this study, we showed that UBE2S and UBE2C were overexpressed while Numb was downregulated in BC, and in BC of higher grade, stage, and poor survival. Compared to hormone receptor negative (HR−) BC cell lines or tissues, HR+ BC demonstrated lower UBE2S/UBE2C and higher Numb, corresponding to better survival. We also showed that increased UBE2S/UBE2C and reduced Numb predicted poor prognosis in BC patients, as well as in ER+ BC patients. In BC cell lines, UBE2S/UBE2C overexpression decreased the level of Numb and enhanced cell malignancy, while knocking down UBE2S/UBE2C demonstrated the opposite effects.ConclusionUBE2S and UBE2C downregulated Numb and enhanced BC malignancy. The combination of UBE2S/UBE2C and Numb could potentially serve as novel biomarkers for BC.

BackgroundPolycystic ovary syndrome (PCOS) not only increases fertility challenges for women of reproductive age, but also leads to increased complications during pregnancy and even affects the birth weight of newborns. Also, hyperandrogenemia is associated with lower pregnancy rates and lower live birth rates and may even play a role in preterm delivery and pre-eclampsia in patients with PCOS. However, it is still controversial whether PCOS patients are treated with androgen-lowering therapy before pregnancy.ObjectiveTo assess the effect of anti-androgen therapy prior to ovulation induction on maternal and infant pregnancy outcomes in patients with PCOS.MethodsProspective cohort study.ResultsA total of 296 patients with PCOS were enrolled in the study. The prevalence of adverse pregnancy outcomes, and neonatal complications was lower in DRSP(with drospirenone ethinyl estradiol tablets (II) pretreatment) group than in NO-DRSP(without drospirenone ethinyl estradiol tablets (II) pretreatment) groups (DRSP vs. NO-DRSP: adverse pregnancy outcomes, 12.16% vs. 27.03%, P=0.001; neonatal complications, 17.16% vs. 36.67%, P0.05).ConclusionOur findings suggest that preconception androgen-lowering therapy in patients with PCOS improves pregnancy outcomes and reduces neonatal complications.

BackgroundIatrogenic tracheoesophageal fistula (TEF) is a rare but life-threatening condition. No consensus has been reached regarding TEF treatment, though, stenting has been gaining popularity for less invasiveness than thoracic surgery. The airway management during stent placement for TEF could be challenging.Case presentationsWe report a patient who suffered from TEF after cardiac surgery with symptoms of persistent coughing and aspiration. He who was admitted for stent placement but ended up in failure and referred to our institution for further treatment. We successfully took advantage of the supraglottic jet oxygenation and ventilation (SJOV) during stent placement.ConclusionThis is the first case so far describing SJOV in complicated stenting treatment. This demonstrates that SJOV can be applied for stent placement in TEF patients with restricted airways.

Preeclampsia (PE) is a severe placenta-related pregnancy disease that has been associated with maternal systemic inflammation and immune system disorders. However, the distribution and functional changes in immune cells of the maternal–placental interface have not been well characterized. Herein, cytometry by time-of-flight mass spectrometry (CyTOF) was used to investigate the immune atlas at the decidua, which was obtained from four PE patients and four healthy controls. Six superclusters were identified, namely, T cells, B cells, natural killer (NK) cells, monocytes, granulocytes, and others. B cells were significantly decreased in the PE group, among which the reduction in CD27+CD38+ regulatory B cell (Breg)-like cells may stimulate immune activation in PE. The significantly increased migration of B cells could be linked to the significantly overexpressed chemokine C-X-C receptor 5 (CXCR5) in the PE group, which may result in the production of excessive autoantibodies and the pathogenesis of PE. A subset of T cells, CD11c+CD8+ T cells, was significantly decreased in PE and might lead to sustained immune activation in PE patients. NK cells were ultimately separated into four subsets. The significant reduction in a novel subset of NK cells (CD56-CD49a-CD38+) in PE might have led to the failure to suppress inflammation at the maternal–fetal interface during PE progression. Moreover, the expression levels of functional markers were significantly altered in the PE group, which also inferred that shifts in the decidual immune state contributed to the development of PE and might serve as potential treatment targets. This is a worthy attempt to elaborate the differences in the phenotype and function of CD45+ immune cells in the decidua between PE and healthy pregnancies by CyTOF, which contributes to understand the pathogenesis of PE, and the altered cell subsets and markers may inspire the immune modulatory therapy for PE.

Objective: To investigate the effect of exposure to multiple ambient air pollutants during pregnancy on the risk of children being born small for gestational age (SGA).Methods: An Air Pollution Score (APS) was constructed to assess the effects of being exposed to six air pollutants simultaneously, PM2.5, PM10, SO2, NO2, CO, and O3 (referred to as joint exposure). A logistic regression model was applied to estimate the associations of APS and SGA.Results: The adjusted odds ratios (ORs) of SGA per 10 ug/m3 increased in APS during the first and second trimesters and the entire pregnancy were 1.003 [95% confidence intervals (CIs): 1.000, 1.007], 1.018 (1.012, 1.025), and 1.020 (1.009, 1.031), respectively. The ORs of SGA for each 10 μg/m3 elevated in APS during the whole pregnancy were 1.025 (1.005, 1.046) for mothers aged over 35 years old vs. 1.018 (1.005, 1.031) for mothers aged under 35 years old. Women who were pregnant for the first time were more vulnerable to joint ambient air pollution.Conclusion: In summary, the results of the present study suggested that joint exposure to ambient air pollutants was associated with the increment in the risks of SGA.

BackgroundLung cancer is a lethal malignant tumor that is common worldwide and is associated with a high incidence of malnutrition. Phase angle (PA) is a simple, objective, and non-invasive indicator of body composition that has increasingly attracted attention as an indicator of the nutritional status and prognosis of patients with malignant tumors. This study aimed to investigate the association between the PA and overall survival in patients with lung cancer.MethodsThis study prospectively analyzed 804 lung cancer patients in the Investigation on Nutrition Status and its Clinical Outcome of Common Cancers (INSCOC) project from 40 hospitals in China. We used a restricted cubic spline to analyze the sex-specific association between PA and mortality in men and women with lung cancer. Cox regression analysis was used to evaluate the independent association between PA and mortality in men and women. Sensitivity analysis was performed. The Kaplan–Meier method was used to evaluate the survival of patients with high and low PA values.ResultsThere was an L-shaped association between PA and survival in both men and women with lung cancer (p = 0.019 and p = 0.121, respectively). Kaplan–Meier survival analysis suggested that patients with a high PA showed a better survival than patients with a low PA (p = 0.007 for men and p < 0.001 for women). Multivariate-adjusted Cox regression analysis showed that PA was an independent risk factor for mortality in men (HR = 0.79, 95% CI = 0.65–0.95, p = 0.015), but not in women (HR = 0.83, 95% CI = 0.67–1.04, p = 0.105).ConclusionPhase angle is an independent risk factor for the mortality of male lung cancer patients. However, its role in predicting the mortality of female lung cancer patients seems to be limited.

BackgroundRapid serial visual presentation (RSVP) has become a popular target detection method by decoding electroencephalography (EEG) signals, owing to its sensitivity and effectiveness. Most current research on EEG-based RSVP tasks focused on feature extraction algorithms developed to deal with the non-stationarity and low signal-to-noise ratio (SNR) of EEG signals. However, these algorithms cannot handle the problem of no event-related potentials (ERP) component or miniature ERP components caused by the attention lapses of human vision in abnormal conditions. The fusion of human-computer vision can obtain complementary information, making it a promising way to become an efficient and general way to detect objects, especially in attention lapses.MethodsDynamic probability integration (DPI) was proposed in this study to fuse human vision and computer vision. A novel basic probability assignment (BPA) method was included, which can fully consider the classification capabilities of different heterogeneous information sources for targets and non-targets and constructs the detection performance model for the weight generation based on classification capabilities. Furthermore, a spatial-temporal hybrid common spatial pattern-principal component analysis (STHCP) algorithm was designed to decode EEG signals in the RSVP task. It is a simple and effective method of distinguishing target and non-target using spatial-temporal features.ResultsA nighttime vehicle detection based on the RSVP task was performed to evaluate the performance of DPI and STHCP, which is one of the conditions of attention lapses because of its decrease in visual information. The average AUC of DPI was 0.912 ± 0.041 and increased by 11.5, 5.2, 3.4, and 1.7% compared with human vision, computer vision, naive Bayesian fusion, and dynamic belief fusion (DBF), respectively. A higher average balanced accuracy of 0.845 ± 0.052 was also achieved using DPI, representing that DPI has the balanced detection capacity of target and non-target. Moreover, STHCP obtained the highest AUC of 0.818 ± 0.06 compared with the other two baseline methods and increased by 15.4 and 23.4%.ConclusionExperimental results indicated that the average AUC and balanced accuracy of the proposed fusion method were higher than individual detection methods used for fusion, as well as two excellent fusion methods. It is a promising way to improve detection performance in RSVP tasks, even in abnormal conditions.

Gastrointestinal (GI) disorders are very common among children with cerebral palsy. Gut microbiota has been confirmed to maintain normal GI physiological function and further contributed to cerebral palsy through the gut-brain axis. Our study was to investigate the effect of dietary fiber combined with probiotics on functional constipated children with cerebral palsy. In total, 35 patient children were enrolled and divided into general diet group (n = 14) and liquid diet group (n = 21). All the participants received Compound Dietary Fiber (CDF) for 1 month and lactic acid-producing and butyric acid-producing probiotics for 6 months. After a 1-month intervention, the frequency of spontaneous and manual defecation, and Bristol score were all significantly improved (P < 0.001). The α-diversity of the gut microbiota was significantly increased after a 1-month intervention (P < 0.05), with a higher abundance of butyric acid-producing bacteria and a lower abundance of opportunistic pathogens (P < 0.05, FDR < 0.05). However, the impersistent effect of the 6-month intervention suggested the insufficient impact of intaking probiotics alone and the short duration of CDF intervention. Moreover, although the intervention had affected the constipation symptoms equally in cerebral palsy children with a general diet and liquid diet, the general diet group showed a greater and more durable change in gut microbiota and clinical phenotypes after intervention than the liquid diet group, which indicated that longer intervention time should be considered for liquid diet children. This study not only illustrated that supplementation of dietary fiber combined with probiotics can improve functional constipation in children with cerebral palsy, but also provides guidance for optimal intervention strategy for future studies, which will further benefit cerebral palsy children.Clinical trial registration:http://www.chictr.org.cn/showproj.aspx?proj=46902, identifier: ChiCTR1900028257.

BackgroundPerivascular epithelioid cell tumors have characteristic histological and immunohistochemical profiles. Epithelioid angiomyolipomas in the liver have particularly rare characteristics. These tumors are relatively small and lack clinical and imaging specificity. Thus, they can be easily misdiagnosed as other primary or metastatic tumors prior to surgery. Due to the significant epithelioid morphology and atypia of hepatic epithelioid angiomyolipoma (HEAML), intraoperative frozen section pathologic diagnosis might be challenging.Case presentationA 33-year-old woman was admitted to our hospital for elevated alpha-fetoprotein (AFP) levels after a regular checkup following breast cancer surgery. Initially, liver cancer was suspected based on enhanced magnetic resonance imaging and color Doppler ultrasonography. Her serum AFP levels were 23.05 ng/ml. The patient underwent laparoscopic right hepatic tumor resection. Based on intraoperative cryopathology, hepatocellular carcinoma was considered a likely diagnosis. However, postoperative pathology confirmed a right HEAML. The patient underwent regular checkups for 23 months without exhibiting recurrence or distant metastasis.ConclusionHEAML can be easily misdiagnosed on preoperative imaging and intraoperative cryopathology. Medical professionals must be aware of this possibility and proceed with caution. Postoperative pathological examination with assessment of IHC markers was helpful in diagnosing HEAML. HEAML has low malignant potential. Surgical resection is the mainstay of treatment, and most patients have a good prognosis.

Background: Immune checkpoint inhibitor (ICI) therapies have revolutionized the treatment of metastatic cutaneous melanoma, but have only benefitted a subset of them. Gene mutations were reported to impact the ICI therapy outcomes in metastatic melanoma but have not been fully investigated. Hence, we systematically analyzed the impact of cancer-related gene mutations on the clinical outcome in metastatic melanoma patients who underwent ICI therapies.Methods: Publicly available discovery and validation cohorts (312 patients and 110 patients respectively, all the patients received ICI therapies) were included in this study. Cox proportional hazards regression analysis was used to assess the association of 468 cancer-related gene mutations with overall survival (OS) in the discovery cohort, and the polygenic hazard score (PHS) was constructed subsequently, and validated in the validation cohort. The Tumor Immune Estimation Resource (TIMER) online tools, which are based on The Cancer Genome Atlas database, were used to analyze the impact of gene mutations on tumor-infiltrated immune cells in melanoma samples.Results: We found eight gene mutations that were significantly associated with the overall survival (BAP1, CARD11, IGF1R, KMT2D, PTPRD, PTPRT, ROS1, and TERT, p < 0.05, mutation frequency >0.05). The PHS, which was based on these genes, was found to effectively discriminate the subset which benefited most from ICI therapies (HR = 1·54, 95%CI, 1.25–1.95; p < 0.001). After adjusting with age, sex, ICI regimes, and tumor mutation burden (TMB), we found that PHS was an independent predictor for the outcome of ICI therapies (adjusted HR = 1.84, 95%CI, 1.22–2.79; p = 0.004). The PHS was validated in the validation cohort (log-Rank p = 0.038). Further research found that CARD11 and PTPRD mutations were significantly associated with more tumor-infiltrated immune cells in melanoma samples.Conclusion: For the first time, we have shown that PHS can independently and effectively predict the ICI therapy outcome in metastatic melanoma, which once validated by larger research, may help the decision-making process in melanoma.

BackgroundThis study discusses the developmental trends and research hotspots in bronchoscopy anesthesia in the past six decades.MethodsThe original and review articles published from 1975 to June 2021 related to bronchoscopy anesthesia were retrieved from the Web of Science Core Collection (WoSCC). Three different scientometric tools (CiteSpace, VOSviewer, and Bibliometrix) were used for this comprehensive analysis.ResultsThere was a substantial increase in the research on bronchoscopy anesthesia in recent years. A total of 1,270 publications were retrieved up to June 25, 2021. Original research articles were 1,152, and reviews were 118, including 182 randomized controlled trials (RCTs). These publications were cited a total of 25,504 times, with a mean of 20.08 citations per publication. The US had the largest number of publications (27.6%) and the highest H-index of 44. The sum of publications from China ranked second (11.5%), with an H-index of 17. Keyword co-occurrence and references co-citation visual analysis showed that the use of sedatives such as dexmedetomidine in the process of bronchoscopy diagnosis and treatment was gradually increasing, indicating that bronchoscopy anesthesia was further progressing toward safety and comfort.ConclusionBased on a bibliometric analysis of the publications over the past decades, a comprehensive analysis indicated that the research of bronchoscopy anesthesia is in a period of rapid development and demonstrated the improvement of medical instruments and surgical options that have significantly contributed to the field of bronchoscopy anesthesia. The data would provide future directions for clinicians and researchers in relation to bronchoscopy anesthesia.

The Zika virus (ZIKV) epidemic poses a substantial threat to the public, and the development of safe and effective vaccines is a demanding challenge. In this study, we constructed a kind of self-assembling nanovaccine which confers complete protection against ZIKV infection. The ZIKV envelop protein domain III (zEDIII) was presented on recombinant human heavy chain ferritin (rHF) to form the zEDIII-rHF nanoparticle. Immunization of mice with zEDIII-rHF nanoparticle in the absence of an adjuvant induced robust humoral and cellular immune responses. zEDIII-rHF vaccination conferred complete protection against lethal infection with ZIKV and eliminated pathological symptoms in the brain. Importantly, the zEDIII-rHF nanovaccine induced immune response did not cross-react with dengue virus-2, overcoming the antibody-dependent enhancement (ADE) problem that is a safety concern for ZIKV vaccine development. Our constructed zEDIII-rHF nanovaccine, with superior protective performance and avoidance of ADE, provides an effective and safe vaccine candidate against ZIKV.

ObjectivesModern breast cancer techniques, such as the deep inspiration breath-hold (DIBH) technique has been applied for left-sided breast cancer. Whether the DIBH regimen is the optimal solution for left-sided breast cancer remains unclear. This meta-analysis aims to elucidate the differences of DIBH and free-breathing (FB) for patients receiving radiotherapy for left-sided breast cancer and provide a practical reference for clinical practice.MethodsRelevant research available on PubMed, Embase, Cochrane Library, and the Web of Science published before November 30, 2021 was independently and systematically examined by two investigators. Data were extracted from eligible studies for assessing their qualities and calculating the standardized mean difference (SMD) and 95% confidence intervals (CIs) using Review Manager software 5.4 (RevMan 5.4).ResultsForty-one studies with a total of 3599 left-sided breast cancer patients were included in the meta-analysis. Compared with FB, DIBH reduced heart dose (Dmean, Dmax, V30, V10, V5), left anterior descending branch (LAD) dose (Dmean, Dmax), ipsilateral lung dose (Dmean, V20, V10, V5), and heart volume significantly. Lung volume increased greatly, and a statistically significant difference. For contralateral breast mean dose, DIBH has no obvious advantage over FB. The funnel plot suggested this study has no significant publication bias.ConclusionsAlthough DIBH has no obvious advantage over FB in contralateral breast mean dose, it can significantly reduce heart dose, LAD dose, ipsilateral lung dose, and heart volume. Conversely, it can remarkably increase the ipsilateral lung volume. This study suggests that soon DIBH could be more widely utilized in clinical practice because of its excellent dosimetric performance.

Candida albicans is the most frequent fungal species responsible for vulvovaginal candidiasis (VVC), which exhibits distinct genetic diversity that is linked with the clinical phenotype. This study aimed to assess the genotypes and clinical characteristics of different C. albicans isolates from VVC patients. Based on multilocus sequence typing (MLST), clade 1 was identified as the largest C. albicans group, which appeared most frequently in recurrent VVC and treatment failure cases. Further study of antifungal susceptibility demonstrated that MLST clade 1 strains presented significantly higher drug resistance ability than non-clade 1 strains, which result from the overexpression of MDR1. The mRNA and protein expression levels of virulence-related genes were also significantly higher in clade 1 isolates than in non-clade 1 isolates. Proteomic analysis indicated that the protein stabilization pathway was significantly enriched in clade 1 strains and that RPS4 was a central regulator of proteins involved in stress resistance, adherence, and DNA repair, which all contribute to the resistance and virulence of MLST clade 1 strains. This study was the first attempt to compare the correlation mechanisms between C. albicans MLST clade 1 and non-clade 1 strains and the clinical phenotype, which is of great significance for VVC classification and treatment.

BackgroundThis study aimed to explore the value of combining the modified geriatric nutrition risk index (mGNRI) and handgrip strength (HGS) in the prognosis assessment of cancer.MethodsThis multicenter, prospective cohort study, enrolled 5,607 cancer patients from 27 medical centers across 17 provinces in China between June 2012 and December 2019. The primary outcome was overall survival. Secondary outcomes included the Karnofsky Performance Scale (KPS) score, Patient-Generated Subjective Global Assessment (PG-SGA) score, cachexia, and admission 90-day outcome. A composite prognostic score (mGNRI-HGS score) was developed based on the mGNRI and HGS. The Kaplan–Meier method was used to draw the survival curve, and log-rank analysis was used to estimate the survival rate. The Cox proportional hazards model was used to investigate the associations of the mGNRI, HGS or mGNRI-HGS score with risk of mortality among the cancer patients, adjusted for potential confounders.ResultsA low mGNRI (HR = 0.99, 95%CI = 0.98–0.99, p < 0.001) and low HGS (HR = 0.99, 95%CI = 0.98–0.99, p = 0.001) were associated with an increased risk of mortality. A severe mGNRI-HGS score was independently associated with reduced survival. Compared with patients with normal scores, the risk of mortality among the patients with moderate and severe mGNRI-HGS scores was 28.8 and 13.3% higher, respectively. Even within the same pathological stage, it presented significant gradient prognostic stratification. Additionally, a low mGNRI-HGS score was also independently associated with a higher risk of low KPS (p < 0.001), high PGSGA (p < 0.001), cachexia (p < 0.001), and adverse admission 90-day outcome (p < 0.001).ConclusionsThe mGNRI and HGS may be useful predictors of long-term prognosis in cancer patients. The combination of the two methods provides effective prognostic stratification for cancer patients and could predict physical frailty, malnutrition, and cachexia.

Pore and pore network evolution of shale is critical for the evaluation the pore system in shale gas reservoirs. Thermal maturation effect acts as an indispensable role in porosity evolution. In this paper, high-temperature and high-pressure in-situ thermal simulation experiments were conducted to investigate the process and controlling factors of pore evolution in marine-continental transitional shale. Multiple methods, including scanning electron microscopy (SEM), X-ray diffraction, helium porosimetry and low-pressure N2 and CO2 adsorption were used to investigate the evolution of mineral composition and pore structure at different stages of thermal maturity. The results showed that type III organic matter (OM) generated petroleum with the thermal maturity increasing. The total organic carbon (TOC) decreased by 13.3% when temperature reached 607°C. At the same time, it produced numerous organic and mineral pores during hydrocarbon generation. Besides, some changes in mineral composition have occurred, especially in illite (from 11% to 31%) and kaolinite (from 89% to 69%). In general, it can divide into 3 stages (maturity, high maturity and over maturity) for shale pore system evolution with the thermal maturity increasing. In the low maturity period, large amounts of pyrolytic bitumen and oil generated to fill the pores, causing the pore system to diminish; in the high maturity period, a large number of pores were generated when oil is cracked into gas, resulting in a rapid expansion of the pore system; in the over-maturity period, the cracking of pyrolysis and hydrocarbon slowed down, allowing the pore system to stabilize. Shale pore evolution is primarily controlled by the thermal evolution of OM, and the conversion of inorganic minerals contributes less to pore evolution compared to organic matter. The high maturity period (1.2% < Ro < 2.0%) was the period when extensive pyrolysis and hydrocarbon generated in the Shanxi Formation shale, which contributed mostly for the pores generation and accumulation of shale gas.

BackgroundHemangioblastoma-like clear cell stromal tumor (HLCCST) is a recently reported neoplasm of the lung. Only 13 cases have been reported in four recent studies. Because HLCCST is very rare, it has not been included in the 2021 WHO classification of lung tumors.Case PresentationWe report a case of HLCCST of the left lower lung in a 40-year-old female who was admitted to our hospital after pulmonary nodules were discovered. A plain chest CT scan showed a nodular high-density shadow measuring approximately 8 mm in diameter in the left lower lung. The lesion had clear borders, uneven internal density, and a low-density central vacuolar area. The left lower lung was partially resected by video-assisted thoracic surgery. Post-operative histopathologic diagnosis “hemangioblastoma-like clear cell stromal tumor” of the left lower lung.ConclusionThe HLCCST is an extremely rare tumor and needs long-term follow-up after operation. Clinically, it may be easily confused with other benign and malignant tumors of the lung, and diagnosis is solely determined by histopathologic examination. This case suggests that immunohistochemical CD34 can be a strong positive marker.

BackgroundFor cancer of unknown primary (CUP), non-selective empiric chemotherapy is usually used. However, patients suffering from CUP are generally assumed to have a dismal prognosis with median overall survival of less than 1 year. Therefore, clinicians eagerly await the establishment of effective strategies for diagnosis and treatment. In recent years, the remarkable advances in next-generation sequencing (NGS) technology have enabled the wide usage of DNA/RNA sequencing to comprehensively analyze the molecular information of individual tumors and identify potential targets for patients’ diagnosis and treatment. Here, we describe a patient of CUP who was successfully diagnosed and treated with targeted therapy directed by comprehensive molecular profiling.Case PresentationA 61-year-old Asian woman with a painless, slow-growing mass lesion in the mesosternum underwent fluorodeoxyglucose-positron emission tomography/computed tomography and was found to have malignant metastatic tumors in the mesosternum. Conventional pathological examination of metastatic lesions could not conclude the primary origin of the tumors. The patient was diagnosed with CUP at first. Then, comprehensive molecular profiling was employed to identify the tumor origin and genetic alterations. A gene expression-based tissue origin assay was performed using a tissue biopsy sample. The test result suggested that the lesion tumors might be breast cancer metastasis. Furthermore, liquid biopsy-based circulating tumor DNA profiling detected an ERBB2 copy number amplification. Subsequent surgery and additional postoperative pathology analysis confirmed that the primary tumor site was indeed located in the right outer upper quadrant of the breast. After local surgical resection, the patient received 8 cycles of Docetaxel + Carboplatin + Trastuzumab + Pertuzumab (TCbHP) chemotherapy with subsequent human epidermal growth factor receptor 2 (HER2)-targeted maintenance therapy. Currently, the patient is on regular follow-up and has achieved disease control for up to 6 months.ConclusionOur findings suggest that molecular identification of the tumor origin and the detection of actionable molecular alterations may offer promise for improved diagnostic accuracy and important therapeutic implications for patients with the CUP syndrome.

IntroductionThe diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. In this study, a novel echocardiography index based on three-dimensional and tissue Doppler echocardiography for diagnosing and estimating prognosis in HFpEF.Materials and MethodsPatients with symptoms and/or signs of heart failure and normal left ventricular ejection fraction (LVEF ≥50%) who underwent right heart catheterization were screened. Patients were divided based on pulmonary capillary wedge pressure (PCWP) of ≥15 mmHg and PCWP

BackgroundPulmonary metastasis of benign uterine leiomyoma and uterine endometriosis has been reported; however, pulmonary benign metastasizing uterine adenomyoma has not been reported. Herein, we report the first case of pulmonary benign metastasizing uterine adenomyoma. It is very important to differentiate from pulmonary primary synovial sarcoma; histopathology and immunohistochemistry are very helpful, molecular pathology can be used if necessary.Case PresentationA female patient was admitted to the hospital because of pulmonary nodules. Lung computed tomography (CT) showed a nodular high density shadow in the upper lobe of the right lung, with a clear boundary and a diameter of approximately 1.2 cm. A contrast CT scan showed obvious enhancement, and no obvious lobulation or burr was found. Video-assisted thoracoscopic resection of the tumor was performed. The upper lobe nodules were completely removed. Postoperative pathological report confirmed the lesion as metastatic benign adenomyoma of the right upper lung.ConclusionThe lung is the most common organ for malignant tumor metastasis, and a few benign tumors can also develop pulmonary metastasis. Pulmonary benign metastasizing adenomyoma is extremely rare, and the prognosis is very good after surgical resection. When pulmonary CT shows a solid high-density shadow, we should consider the possibility of a metastatic benign tumor.

Preeclampsia (PE) is a serious disease during pregnancy that affects approximately eight million mothers and infants worldwide each year and is closely related to abnormal trophoblast function. However, research on placental trophoblast functional abnormalities is insufficient, and the etiology of PE is unclear. Here, we report that the expression of transgelin-2 (TAGLN2) was downregulated in the placenta of patients with PE. In addition, a lack of TAGLN2 significantly reduced the ability of trophoblasts to migrate, invade and fuse. A co-immunoprecipitation (Co-IP) and microscale thermophoresis analysis showed that TAGLN2 bound directly to E-cadherin. A decrease in TAGLN2 expression led to a reduction in cleavage of the E-cadherin extracellular domain, thereby regulating the function of trophoblasts. In addition, we found that a reduction in soluble E-cadherin may also have an effect on blood vessel formation in the placenta, which is necessary for normal placental development. What’s more, the in vivo mouse model provided additional evidence of TAGLN2 involvement in the development of PE. By injecting pregnant mice with Ad-TAGLN2, we successfully generated a human PE-like syndrome that resulted in high blood pressure and some adverse pregnancy outcomes. Overall, the association between TAGLN2 and PE gives a new insight into PE diagnosis and treatment.

Osteoporosis is alarming problem due to aggravation of global aging, especially in China. Osteoporotic fracture (OF) is one of the most severe consequents of osteoporosis. Many previous studies found that environmental factors had adverse effects on human health. Cold temperature was associated with OF and bone metabolism in prior observational and experimental researches. However, few studies had been conducted on the acute effect of low temperature and OF. Data on daily meteorological factors and hospitalizations for OF were collected from Wuhan, China, between January 1, 2017 to December 24, 2019. Apparent temperature (AT), comprehensively considered a variety of environmental factors, was calculated by ambient temperature, relative humidity and wind speed. A generalized linear regression model combined with distributed lag non-linear regression model (DLNM) with quasi-Poisson link was used to explore the association between AT and the number of hospitalizations for OF. Subgroup analyses stratified by gender, age and the history of fracture were applied for detecting susceptible people. The exposure-response curve of AT and OF were generally U-shaped with lowest point at 25.8°C. The significant relationship of AT-OF existed only in cold effect (−2.0 vs. 25.8°C) while not in warm effect (37.0 vs. 25.8°C). Statistically significant risks of OF for cold effects were only found in females [RR = 1.12 (95%CI: 1.02, 1.24) at lag 2 day], aged