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Objective. Shen-Ling-Bai-Zhu-San (SLBZS) is used for treating gastrointestinal disorders. However, the role of SLBZS in treating pneumonia in children is still unclear. Methods. In this study, children (≥2 and

Background: Actinomycosis and mucormycosis are very uncommon in clinical work, a combination of both two infection is much rarer in one host. Actinomycosis of the trachea is a chronic septic disease caused by an actinomycete infection with a very low incidence. It is easily misdiagnosed owing to the difficulty in obtaining microbiological evidence. Likewise, mucormycosis is a rare conditionally pathogenic invasive fungal infection, but with an abrupt start, quick progression, and extremely high mortality. It is frequently observed in individuals with immunosuppression-related disorders. The infection is rare in one host with both of the two above pathogens, and the site of infection involving only the main bronchi is even more uncommon, which is why we report the following case. Case description: The patient, a 58-year-old lady, has a long history of diabetes and has trouble controlling her blood sugar. A whitish mass in the main bronchus was discovered via fiberoptic bronchoscopy as a result of breathing difficulties. Then, the diagnosis of complex intratracheal actinomycosis with mucor infection was supported by a pathological biopsy. After an active combination treatment with bronchoscopic cryotherapy, Holmium Laser coupled with amphotericin B and penicillin, the patient was successfully discharged. Conclusions: Clinically, when imaging reveals intratracheal protuberant lesions, further fiberoptic bronchoscopy and an etiological investigation should be carried out as soon as feasible in order to prevent misdiagnosis and missed diagnosis.

Background HIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the ‘CDC-Public Security Bureau-NGO’. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions. Methods An 8-year consecutive cross-sectional survey, including a 4-year traditional intervention (2014-2017) and the 4-year ‘CDC-Public Security Bureau-NGO’ innovative intervention (2018-2021), was conducted to evaluate the effects of the new intervention. Compared to the traditional intervention, the ‘CDC-Public Security Bureau-NGO’ intervention achieved positive effects by decreasing risky behaviours. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018–2021; P and C values were used to evaluate the performance of the model. Results The most recent condom use rate among female sex workers and elderly clients has increased from 81.1% to 95.3% (P < 0.05), newly reported cases of HIV have decreased by 15.56% yearly and the HIV infection rate among middle-aged and elderly people has dropped by 19.91% yearly. The innovative intervention model has significantly reduced the HIV infection rates. Conclusions The ‘CDC-Public Security Bureau-NGO’ innovative intervention has achieved beneficial effects on HIV/AIDS prevention and control and provides a good reference for Guangxi, China.

Supplementary Data from HJM-561, a Potent, Selective, and Orally Bioavailable EGFR PROTAC that Overcomes Osimertinib-Resistant EGFR Triple Mutations

Supplementary Figure from HJM-561, a Potent, Selective, and Orally Bioavailable EGFR PROTAC that Overcomes Osimertinib-Resistant EGFR Triple Mutations

The EGFR C797S mutation is the most common on-target resistance mechanism to osimertinib in patients with advanced non–small cell lung cancer (NSCLC). Currently there are no effective treatment options for patients with NSCLC harboring EGFR C797S triple mutants (Del19/T790M/C797S and L858R/T790M/C797S). Herein, we report an orally bioavailable EGFR PROTAC, HJM-561, which selectively degrades the EGFR C797S-containing triple mutants. HJM-561 potently inhibits the proliferation of Del19/T790M/C797S and L858R/T790M/C797S Ba/F3 cells while sparing cells expressing wild-type EGFR. Oral administration of HJM-561 shows robust antitumor activity in EGFR Del19/T790M/C797S-driven Ba/F3 CDX and PDX models that were resistant to osimertinib treatment. Taken together, our results suggest that HJM-561 is a promising therapeutic option for overcoming EGFR triple mutation-mediated drug resistance in NSCLC.

Diabetes is a complex metabolic disease that has been associated with epigenetic changes. External factors such as dietary patterns can induce an imbalance in the pools of micronutrients and macronutrients in the body. Consequently, bioactive vitamins may influence epigenetic mechanisms via several pathways: involvement in the control of gene expression, and in protein synthesis, by acting as coenzymes and co-factors in the metabolism of methyl groups or methylation of DNA and histones. Herein, we present a perspective on the relevance of bioactive vitamins in the epigenetic modifications that occur in diabetes.

Background Cancer patients with financial toxicity experience psychological distress and often miss medical appointments and quit treatments early, which could be a barrier to the effective management of oral chemotherapy drugs at home. This study explores whether financial toxicity predicts symptoms and unplanned healthcare utilization among cancer patients taking oral chemotherapy at home, which will contribute to the safe management of oral chemotherapy. Methods Data in this study was from a prospective observational study, which was conducted between October 2018 and December 2019. 151 patients completed the Comprehensive Score for Financial Toxicity at discharge and completed the MD Anderson Symptom Inventory and unplanned healthcare utilization questionnaires after finishing one cycle of oral chemotherapy at home. Regression analyses were conducted to explore the associations of financial toxicity with symptoms and unplanned healthcare utilization. Results Among 151participants, 88.08% reported severe or moderate financial toxicity, 43.05% reported symptom interference, and 31.79% reported unplanned healthcare utilization while taking oral chemotherapy at home. Patients between the age of 45-60y (p = 0.042) have higher financial toxicity, while those living in urban areas (p = 0.016) have lower financial toxicity. Patients with worse financial toxicity suffered increased symptoms of fatigue, emotional distress, disturbed sleep, and lack of appetite. Consequently, their mood and personal relation with other significant suffered. However, no statistical differences in unplanned healthcare utilization were found among patients with different levels of financial toxicity. Conclusion Middle-aged adults and those living in suburban or rural areas experienced worse financial toxicity than other groups. Patients with worse financial toxicity experienced more severe psychological symptoms (e.g., fatigue, distress, disturbed sleep, and lack of appetite) and affective interference (e.g., mood and relations with others). Identifying at-risk patients is necessary to offer tailored support for psychological symptom management.

To address the unequal-area dynamic facility layout problem (UA-DFLP), an optimization method of dynamic facility layout under fixed-point movement strategy was proposed in this paper. Firstly, mathematical models of dynamic facility layout in several production planning period were constructed. Secondly, according to the logistics relationship between facilities, the fixed-point movement strategy was proposed to solve the problem of non-interference constraint processing in the unequal area dynamic facility layout. Then, a genetic simulated annealing algorithm (GSA) for static facility layout and a genetic algorithm (GA) for dynamic facility layout were designed to solve the UA-DFLP by two steps. The first step, the GSA was applied to solve the optimal layout in each phase with the objective of minimizing material handling cost (MHC), and the isomorphic layout corresponding to the optimal layout in each phase was evolved by mirroring and rotation operation; The second step, according to the optimal layout and feasible isomorphic layout of each phase, GA was applied to solve the dynamic layout scheme aiming at minimizing the sum of MHC and facility replacement cost. Finally, the case study shows that the proposed layout method was an effective method to solve the UA-DFLP by three groups of examples.

As a result of the trend toward economic globalization, the vigorous development of cross-border e-commerce has attracted many scholars to study this field, involving many related fields, such as consumer behavior, advertising, information systems, and supply chain management. Throughout the existing literature, it can be found that most of the research focuses on certain influencing factors of the development of cross-border e-commerce, and there is no systematic and macro- overview of the development trend of research in this field in recent years, nor the integration and analysis of keywords. Given that the research in the field of cross-border e-commerce is fragmented to a large extent, to effectively explore the research trend in this field, we must understand the current situation of cross-border e-commerce. Systematic bibliometric analysis can solve this problem by providing publishing trends and information on various topics. Therefore, based on the scientific database web, this study collected 198 references related to cross-border e-commerce from 2016 to 2021, briefly introduced the current situation and development trend of cross-border e-commerce, visually analyzed and refined the journals, authors, research institutions, countries, publication years, keywords, citations of academic publications in this field, and other key information, and summarized the development trend and path of CEBC in the existing research. It is helpful for researchers to solve the current research gap, understand the future research direction in this field, and help academia establish a strict knowledge system.

With aging, iron will accumulate in the brain, catalyzing oxidative radicals that damage brain neurons and induceAlzheimer's disease. In this experiment, we observed that in the brains of senile mice, the iron-exporting protein ferriportin was decreased. Further investigation indicated that H3K27 of the slc40a1 gene was methylated and that the methyltransferase Ezh2 was activated. To discharge the excessive iron in the brains of senile mice, we developed the YP peptide, and with it, we demethylated H3K27me of Slc40a1 by phosphorylation, activating the demethylase Kdm6a and inhibiting methyltransferase Ezh2. Consequently, the transcription of Slc40a1 was enhanced,and ferriportin was resumed. Thesenile brain reacquired the function of iron excretion, and as a result, the radicals in the brain weredecreased,and neuron damage was reduced, which finally restored the intelligence of dementia senile mice. Thus, YP could be a potential drug in the prevention of Alzheimer's disease

Acute myeloid leukemia (AML) is a hematological malignancy characterized by cytogenetic and genomic alterations. Up to now, combination chemotherapy remains the standard treatment for leukemia. However, many individuals diagnosed with AML develop chemotherapeutic resistance and relapse. Recently, it has been pointed out that leukemic stem cells (LSCs) are the fundamental cause of drug resistance and AML relapse. LSCs only account for a small subpopulation of all leukemic cells, but possess stem cell properties, including a self-renewal capacity and a multi-directional differentiation potential. LSCs reside in a mostly quiescent state and are insensitive to chemotherapeutic agents. When LSCs reside in a bone marrow microenvironment (BMM) favorable to their survival, they engage into a steady, continuous clonal evolution to better adapt to the action of chemotherapy. Most chemotherapeutic drugs can only eliminate LSC-derived clones, reducing the number of leukemic cells in the BM to a normal range in order to achieve complete remission (CR). LSCs hidden in the BM niche can hardly be targeted or eradicated, leading to drug resistance and AML relapse. Understanding the relationship between LSCs, the BMM, and the generation and evolution laws of LSCs can facilitate the development of effective therapeutic targets and increase the efficiency of LSCs elimination in AML.

Purpose Vessel segmentation from volumetric medical images is becoming an essential pre-step in aiding the diagnosis, guiding the therapy, and patient management for vascular-related diseases. Deep learning-based methods have drawn many attentions, but most of them did not fully utilize the multi-scale spatial information of vessels. To address this shortcoming, we propose a multi-scale network similar to the well-known multi-scale DeepMedic. It also includes a double-pathway architecture and a class-balanced loss at the voxel level (MDNet-Vb) to achieve both the computation efficiency and segmentation accuracy. Methods The proposed network consists two parallel pathways to learn the multi-scale vessel morphology. Specifically, the pathway with a normal resolution uses three-dimensional (3D) U-Net fed with small inputs to learn the local details with relatively small storage and time consumption. The pathway with a low-resolution employs 3D fully convolutional network (FCN) fed with downsampled large inputs to learn the overall spatial relationships between vessels and adjacent tissues, and the morphological information of large vessels. To cope with the class-imbalanced issue in vessel segmentation, we propose a class-balanced loss at the voxel level with uniform sampling strategy. The class-balanced loss at the voxel level re-balances the loss function with a coefficient that is inversely proportional to the normalized effective number at the voxel level of each class. The uniform sampling strategy extracts training data by sampling uniformly from two classes in every epoch. Results Our MDNet-Vb outperforms several state-of-the-art methods including ResNet, DenseNet, 3D U-Net, V-Net, and DeepMedic with the highest dice coefficients of 72.91% and 69.32% on cardiac computed tomography angiography (CTA) dataset and cerebral magnetic resonance angiography (MRA) dataset, respectively. Among four different double-pathway networks, our network (3D U-Net+3D FCN) not only has the fewest training parameters and shortest training time, but also gets competitive dice coefficients on both the CTA and MRA datasets. Compared with classical losses, our class-balanced focal loss (FL-Vb) and dice coefficient loss at the voxel level (Dsc-Vb) alleviates class imbalanced issue by improving both the sensitivity and dice coefficient on the CTA and MRA datasets. Moreover, simultaneously training on two datasets shows that our method has the highest dice coefficient of 73.06% and 65.40% on CTA and MRA datasets, respectively, outperforming the commonly used methods, such as U-Net and DeepMedic, which demonstrates the generalization potential of our network for segmenting different blood vessels. Conclusions Our MDNet-Vb method demonstrates its superiority over other state-of-the-art methods, on both cardiac CTA and cerebral MRA datasets. For the network architecture, the MDNet-Vb combined the 3D U-Net and 3D FCN, which dramatically reduces the network parameters yet maintains the segmentation accuracy. The class-balanced loss at the voxel level further improves accuracy by properly alleviating the class-imbalanced issue between different classes. In summary, MDNet-Vb is promising for vessel segmentation from various volumetric medical images.

Selective induction of tumor thrombus infarction is a promising antitumor strategy. Non-persistent embolism due to non-compacted thrombus and activated fibrinolytic system within the tumor large blood vessels and tumor margin recurrence are the main therapeutic bottlenecks. Herein, an erythrocyte membrane-coated invisible acoustic-sensitive nanoparticle (TXA+DOX/PFH/RBCM@cRGD) is described, which can induce tumor thrombus infarction by precisely damaging tumor vascular endothelium. It is revealed that TXA+DOX/PFH/RBCM@cRGD can effectively accumulate on the endothelial surface of tumor vessels with the help of the red blood cell membrane (RBCM) stealth coating and RGD cyclic peptide (cRGD), which can be delivered in a targeted manner as nanoparticle missiles. As a kind of phase-change material, perfluorohexane (PFH) nanodroplets possess excellent acoustic responsiveness. Acoustic-sensitive missiles can undergo an acoustic phase transition and intense cavitation with response to low-intensity focused ultrasound (LIFU), damaging the tumor vascular endothelium, rapidly initiating the coagulation cascade, and forming thromboembolism in the tumor vessels. The drugs loaded in the inner water phase are released explosively. Tranexamic acid (TXA) inhibits the fibrinolytic system, and doxorubicin (DOX) eliminates the margin survival. In summary, a stealthy and acoustically responsive multifunctional nanoparticle delivery platform is successfully developed for inducing thrombus infarction by precisely damaging tumor vascular endothelium.

Atrial fibrillation (AF) is a common atrial arrhythmia for which there is no specific therapeutic drug. Quercetin (Que) has been used to treat cardiovascular diseases such as arrhythmias. In this study, we explored the mechanism of action of Que in AF using network pharmacology and molecular docking. The chemical structure of Que was obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank, STITCH, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF and normal tissue by GEO database differentially expressed genes by GEO database. The top targets were IL6, VEGFA, JUN, MMP9 and EGFR, and Que for AF treatment might involve the role of AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking showed that Que binds strongly to key targets and is differentially expressed in AF. In vivo results showed that Que significantly reduced the duration of AF fibrillation and improved atrial remodeling, reduced p-MAPK protein expression, and inhibited the progression of AF. Combining network pharmacology and molecular docking approaches with in vivo studies advance our understanding of the intensive mechanisms of Quercetin, and provide the targeted basis for clinical Atrial fibrillation treatment.

Pemphigus is a rare autoimmune blistering disease, involving potentially life-threatening conditions often requiring immunosuppression. Currently, the COVID-19 pandemic caused by severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection has become a global public emergency. Vaccines are the most effective defense against COVID-19 infection. However, in clinic, there are cases of new onset or flare of pemphigus following COVID-19 vaccination, where vaccines have manifested significantly desirable risk-benefit profiles for patients. Although Rituximab, as first-line therapy, may impair humoral immunity, pemphigus may not predispose to develop COVID-19 infection compared to a healthy population. Conversely, delay or interruption of immunosuppressants probably results in unfavorable clinical outcomes for disease progression. Overall, clinicians should encourage their patients to undergo the vaccination after a comprehensive assessment. The definite association between COVID-19 vaccination and pemphigus remains to be further elucidated. Herein, we provide an overview of the published studies to date on COVID-19 and pemphigus as well as the exploration of their complicated interplay. In addition, we discuss the management strategies for pemphigus patients in this special period, in an effort to more effectively establish a standard treatment paradigm for this particular patient group.

Background: Since lung cancer (LC) has a poor prognosis worldwide, this study focuses on constructing the immune-related lncRNAs (IRlncRNAs) model for improving survivability among lung cancer patients.Methods: This work identified immune-related differentially expressed genes (IRDEGs) in cancer compared with healthy tissues based on The Cancer Genome Atlas (TCGA)-derived expression profiles. Prognostic genes were later screened by univariate Cox regression, thereafter, multivariate Cox regression was performed to establish a prognostic risk model. After evaluating risk scores of all cases, the risk model was used to perform a clinical correlation analysis.Results: This work established a 6 immune-related genes (IRGs)-based signature. It suggested the poor survival of high-risk patients, with the area under the receiver operating characteristic (ROC) curve (AUC) value being 0.776. Besides, high-risk IRGs like IPO5P1 and AC090559.1 were associated with significant malignant clinical manifestations. Further, IRlncRNAs were related to cell cycle and DNA damage repair through KEGG enrichment analysis.Conclusion: Our as-constructed signature might be the model to effectively predict LC survival. Moreover, tumor immunity analysis helped to develop efficient clinical treatments.

In the mathematical model of the optimal operation of a single pump unit with a fully adjustable blade in the Chinese South-to-North Water Diversion Project, the decision variable, namely, blade angle, was uniformly dispersed in its feasible region in a fixed step size in consideration of the requirements of the pumping head and matching motor power. 1D dynamic programming was applied to solve the original model. When the obtained blade for each time period was set as the middle reference value and the discrete region of the blade was reduced to two times of the step size in the previous time, the blade angle was correspondingly reduced and dispersed in this new discrete region, thus eliminating unnecessary optimization space. Then, 1D dynamic programming was applied again to optimize the blade angle of the single pump unit further. After a series of successive approximation discretization of the blade angle and corresponding solutions of the obtained mathematical model, the optimization process was considered completed when the given control precision met the requirement. A case study showed that under typical operating conditions, the total cost saving percentage of water pumping quantity reached 0.048%–0.463%, with an average saving rate of 0.192%. The actual total water pumping quantity of the single unit decreased by 2153 m3 on the average. The proposed discretization method exerted a better optimization effect and needed a smaller computational amount compared with traditional one-time uniform discretization in the original feasible region of the blade angle.

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

BackgroundPsoriasis is an immune-related skin disease notable for its chronic inflammation of the entire system. Alzheimer’s disease (AD) is more prevalent in psoriasis than in the general population. Immune-mediated pathophysiologic processes may link these two diseases, but the mechanism is still unclear. This article aimed to explore potential molecular mechanisms in psoriasis and AD.MethodsGene expression profiling data of psoriasis and AD were acquired in the Gene Expression Omnibus (GEO) database. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were first applied in two datasets. Differentially expressed genes (DEGs) of two diseases were identified, and common DEGs were selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to explore common biological pathways. Signature transcription factors (STFs) were identified and their diagnostic values was calculated by receiver operating characteristic (ROC) curve analysis in the exploration cohort and verified in the validation cohort. The expression levels of STFs were further investigated in the validation cohort and the GTEx Portal Database. Additionally, four kinds of interaction analysis were performed: correlation analysis among STFs, gene-gene, chemical-protein, and protein-ligand interaction analyses. In the end, we predicted the transcription factor that potentially regulates STFs.ResultsBiosynthesis and metabolic pathways were enriched in GSEA analysis. In ssGSEA analysis, most immunoreaction gene lists exhibited differential enrichment in psoriasis cases, whereas three receptor-related gene lists did in AD. The KEGG analysis of common DEGs redetermined inflammatory and metabolic pathways essential in both diseases. 5 STFs (PPARG, ZFPM2, ZNF415, HLX, and ANHX) were screened from common DEGs. The ROC analysis indicated that all STFs have diagnostic values in two diseases, especially ZFPM2. The correlation analysis, gene-gene, chemical-protein, and protein-ligand interaction analyses suggested that STFs interplay and involve inflammation and aberrant metabolism. Eventually, ZNF384 was the predicted transcription factor regulating PPARG, ZNF415, HLX, and ANHX.ConclusionsThe STFs (PPARG, ZFPM2, ZNF415, HLX, and ANHX) may increase the morbidity rate of AD in psoriasis by initiating a positive feedback loop of excessive inflammation and metabolic disorders. ZNF384 is a potential therapeutic target for psoriasis and AD by regulating PPARG, ZNF415, HLX, and ANHX.

It is well known that the difficulty of siRNA therapeutic application is the lack of safe and effective delivery vector. Virosome is a nano vesicle composed of lipid membrane and membrane protein. It retains fusion protein without virus genetic material, and therefore has the reduced immunogenicity compared with viral vector. Virosomes have the potential to deliver protein and nucleic acid drugs, but the traditional preparation method of virosomes is quite limited. In this study, we firstly proposed to synthesize influenza virus hemagglutinin HA2 virosomes by cell-free protein synthesis. In this study, liposomes provided the hydrophobic lipid bilayer environment for the formation of HA2 protein multimer, which inhibited the aggregation of hydrophobic HA2 and improved HA2 protein expression. Chitosan as a rigid core adsorbed siRNA and improved the encapsulation efficiency of siRNA. In conclusion, the cell-free protein synthesis was used to prepare HA2 virosomes, which paves the way for constructing a novel nano vector with high delivery efficiency and biosafety for the delivery of siRNA.

Background Lung carcinoma is a common geriatric disease. The development of genotype-targeted therapies greatly improved the management of lung carcinoma. However, the treatment for old patients can be more complex than that for young individuals. Results To investigate the benefits of genetic detection for older patients with lung carcinoma, we explored the genomic profiling of 258 patients with more than 55 years using a targeted next generation sequencing, and some of these patients were treated with targeted therapies based on the results of genomic detection. KRAS codon 61 mutations were found in 15.2% KRAS-mutated patients, which tend to be co-existing with other classical activating mutations other than codons 12/13. Acquired EGFR C797S mutations were identified in 2 cases and ERBB2 amplification was identified in 1 case. All these 3 cases developed resistance to EGFR tyrosine kinase inhibitors and showed expected results of their followed therapies. The median progression-free survival and median overall survival of patients treated with molecular targeted therapies were better than those of patients treated with chemoradiotherapy alone. Conclusions Our findings revealed the specific genomic profiles of patients older than 55 years with lung carcinoma and suggested that these old patients have been benefit from the genetic detection, which helped identify druggable mutations and distinguish resistance mechanisms.

PurposeAtrial fibrillation (AF) is a common atrial arrhythmia. Quercetin (Que) has some advantages in the treatment of cardiovascular disease arrhythmias, but its specific drug mechanism of action needs further investigation. To explore the mechanism of action of Que in AF, core target speculation and analysis were performed using network pharmacology and molecular docking methods.MethodsQue chemical structures were obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank , STITCH, Binding DB, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF from normal tissues by GEO database differentially expressed genes. Then, the intersecting genes were obtained by online Wayne mapping tool. The intersection genes were introduced into the top five targets selected for molecular docking via protein-protein interaction (PPI) network to verify the binding activity between Que and the target proteins. GO and KEGG enrichment analysis of the intersected genes using program R was performed to further screen for key genes and key pathways.ResultsThere were 65 effective targets for Que and AF. Through further screening, the top 5 targets were IL6, VEGFA, JUN, MMP9 and EGFR. Que treatment of AF may involve signaling pathways such as lipid and atherosclerosis pathway, AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking suggests that Que has strong binding to key targets.ConclusionThis study systematically elucidates the key targets of Que treatment for AF and the specific mechanisms through network pharmacology as well as molecular docking, providing a new direction for further basic experimental exploration and clinical treatment.

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.

Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.

In this work, a novel ratiometric electrochemical sensor based on dual-functional poly-dopamine (PDA) and nickel sulfide@hollow carbon spheres (NiS@HCS) was successfully developed for sunset yellow (SY) detection. The NiS@HCS nanocomposite possessing a large specific surface area, good catalytic activity and excellent electrical conductivity was employed for signal amplification. PDA films prepared by electropolymerization acted as an internal reference probe and enhanced the sensitivity of the proposed sensor through electrostatic attraction between SY and PDA. Under optimized conditions, the developed PDA/NiS@HCS/GCE sensor allowed SY quantification over wide linear range (0.01-100 μM), with a low limit of detection of 0.003 μM. SY recovery tests were carried out in rice vinegar and cooking wine with satisfactory recoveries (83.50-112.80 %). Meanwhile, the content of SY in two kinds of carbonated drinks was determined using the constructed sensor and a UV-Vis spectrometry method, with no significant difference found in the results.

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, and the WHO declared it a pandemic on March 11, 2020. Clinical characteristics and epidemiology features of patients infected with SARS-CoV-2 have been explored in the previous study. However, little is known about the combinative association of liver dysfunction and abnormal interleukins (ILs) in severe patients with COVID-19. This study was designed to estimate whether liver dysfunction and abnormal ILs could predict the severity of COVID-19. This study integrated liver function data and ILs data in patients with COVID-19 and found that liver injury and two ILs, interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6), were closely related to the prognosis of patients with COVID-19. This study may give more exact information to clinicians about the prognosis of patients with COVID-19. In addition, this correlational study between liver disorder and ILs may provide a new vision to diagnosis and treatment in patients.

The coronavirus disease 2019 (COVID-19) may cause cytokine storm and respiratory illness such as pneumonia and progressive respiratory failure. Tocilizumab (TCZ), a monoclonal antibody that targets the interleukin-6 (IL-6) receptor, was approved as an alternative treatment for severe COVID-19 patients despite limited real-world clinical data in China. In the present study, we will discuss and evaluate the treatment response of TCZ therapy in patients with COVID-19. The clinical characteristics, treatment, laboratory parameters of IL-6, C-reactive protein (CRP), lymphocyte counts before and after TCZ therapy, and clinical outcomes in the 13 patients with COVID-19 were retrospectively evaluated according to the related medical records. The results showed that 13 patients with COVID-19 were totally included in this study. One of them was moderately ill, 8 were seriously ill, and 4 were critically ill. Eleven patients received TCZ administration once, while the other 2 patients received it twice. The median level of IL-6 before TCZ administration was 27.91 (7.42–210.90) pg/mL. Serum IL-6 level tended to further spike firstly and then gradually decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL-6 was observed in 2 patients who were finally dead. The CRP levels of 76.92% (10/13) of the patients were above the normal range before the start of TCZ therapy and gradually declined after the TCZ treatment. No. 1 and No. 10 patients finally died accompanied by the corresponding lymphocyte counts persistently dropping. No. 13 patient became exacerbated possibly due to inducing severe bacterial infection after TCZ treatment, while the other 10 patients showed clinical improvement. In summary, the study revealed that TCZ may have a certain therapeutic effect on severe COVID-19 patients with a risk of the cytokine storm. It is necessary to further evaluate the efficacy and safety of TCZ by rigorous randomized controlled trial in the next step.

To explore whether medication non-adherence experience, readiness for hospital discharge, financial toxicity and symptoms predicted oral chemotherapy adherence at home for Chinese cancer patients.Oral chemotherapy adherence is critical to determine the treatment efficacy among cancer patients. Identifying predictors before discharge from hospital based on transition theory could assist healthcare providers to improve oral chemotherapy adherence at home.An observational prospective study.Between October 2018 and December 2019, self-reported questionnaires were used to collect data among 151 cancer patients with oral chemotherapy at home. At discharge, baseline data of patient-perceived readiness for hospital discharge, financial toxicity and non-adherence experience were collected, while symptoms and adherence of oral chemotherapy at home were collected after finishing one cycle of oral chemotherapy at home (21 days, the first 14 days received oral chemotherapy). Regression analyses were performed for the predictors' explorations. The STROBE guidelines were followed.Among 151 participants with oral chemotherapy at home, 30.46% of patients reported medication non-adherence experience at discharge and 82.12% of patients reported adherence to oral chemotherapy at home. Patients with non-adherence experience at discharge were 5.4 times more likely to being non-adhered to oral chemotherapy at home. Numbness were the most frequent and severe symptoms during at home, patients with numbness were 6.6 times more likely to being non-adhered to oral chemotherapy. Although patients reported high level of readiness for discharge and financial toxicity at discharge, which did not predicted oral chemotherapy adherence at home.Patients with medication non-adherence experience at discharge and symptom of numbness from oral chemotherapy suggested a higher risk of oral chemotherapy non-adherence at home.Preventive interventions should focus on patients with previous medication non-adherence experience at discharge and experiencing numbness to promote oral chemotherapy adherence.

BACKGROUND Both healthcare provider-patient communication and self-care efficacy affect psychological distress, which is prevalent among patients with gastrointestinal (GI) cancers. It is essential to explore the underlying mechanism among them to relieve psychological distress. OBJECTIVE The aim of this study was to examine whether self-care efficacy mediated the association between healthcare provider-patient communication and psychological distress among patients with GI cancers. METHODS A cross-sectional study was conducted between March 2018 and May 2019 in China. In total, 219 patients with GI cancers were recruited before discharge from chemotherapy. Healthcare provider-patient communication was assessed by the revised Physician-Patient Communication Scale; patient self-care efficacy was assessed by the Strategies Used by People to Promote Health; and psychological distress was assessed by the Distress Thermometer and the Hospital Anxiety and Depression Scale. Mediation analyses were conducted to examine the mediating effect of self-care efficacy on the association between healthcare provider-patient communication and psychological distress. RESULTS A total of 54.34% of patients experienced psychological distress. Patients reported a mean score of 89.93 (SD, 13.81) for healthcare provider-patient communication and 93.91 (SD, 23.39) for self-care efficacy. Self-care efficacy completely mediated the association between healthcare provider-patient communication and psychological distress, and communication outcome was the only domain that significantly influenced self-care efficacy. CONCLUSION Psychological distress is prevalent among patients with GI cancers. Healthcare provider-patient communication, especially communication outcome, promoted patients' self-care efficacy to reduce psychological distress. IMPLICATIONS FOR PRACTICE Healthcare providers should design interventions to improve communication outcomes and eventually increase self-care efficacy to relieve psychological distress among patients with GI cancers.

An electrochemical sensor based on stearyl trimethyl ammonium bromide - functionalized niobium carbide@multi-walled carbon nanotubes (Nb

Real-life data on guselkumab in psoriasis are limited and not available in China hitherto. This study aimed to evaluate the short-term effectiveness and safety of guselkumab in patients with psoriasis under Chinese real-life conditions and to explore the effect of guselkumab on CD4+ CD25+ Foxp3+ regulatory T cells (Tregs). A Chinese prospective and real-life study involving patients with psoriasis in Dermatology Hospital of Southern Medical University, Guangzhou, China from April to September 2020 was conducted. A total of 45 patients with psoriasis were finally enrolled in the study. Psoriasis Area Severity Index (PASI) 90 and 100 responses at week 16 were achieved by 88.6% and 45.5% of patients, respectively. The analysis of PASI response in different subgroups showed no statistically significant difference. Univariate logistic regression analysis revealed that at week 16, none of the variables were associated with decreasing PASI 90 response, whereas age at onset of disease was a predictor of PASI 100 response. Dynamic detection of CD4+ CD25+ Foxp3+ Tregs frequency from peripheral blood suggested a stable maintained trend in terms of guselkumab treatment duration. No severe adverse events occurred during the follow-up period. This study confirmed the short-term effectiveness and safety of guselkumab, as well as its good tolerance against psoriasis, in the Chinese population. Guselkumab treatment maintains levels of Tregs in patients with psoriasis.

At present, there is limited research on pregnancy body image and no valid tool to measure body image in pregnant Chinese women. The purpose of this study was to translate the Body Understanding Measure Pregnancy Scale into Chinese to determine its reliability and validity in measuring body image in pregnant women.The translation of the Body Understanding Measure Pregnancy Scale (BUMPs) was carried out with a standardized procedure. This study was conducted from July to December 2020 in the outpatient department of three tertiary hospitals in China. There were 1069 pregnant women completed the questionnaire and 1057 of those women were included in the analysis. Internal consistency, test-retest reliability, content validity, and construct validity of the translation version were examined.The final Chinese version of the BUMPs (BUMPs-C) had four dimensions with 16 items. Exploratory factor analysis obtained a three-factor solution, which explained 50.26% of the total variances. Confirmatory factor analysis showed that the model fit of the four-factor model was better than the three-factor model, and the four-factor model also reached a satisfactory model fit after modifying: Minimum Discrepancy was 2.82; Comparative Fit Index was 0.939, and Tucker-Lewis Index was 0.92; Root Mean Square Error of Approximation was 0.059. The content validity index of the scale was 1.0; the Cronbach's alpha (α) coefficient was 0.82 for the total scale, the McDonald's omega (ω) coefficient was 0.829; the test-retest reliability was 0.796.The BUMPs-C showed good reliability and validity among pregnant Chinese women, which can be used as a simple and valid measurement tool to assess the feelings of pregnant Chinese women on body changes during pregnancy.

Long non‐coding RNAs (lncRNAs) play critical roles in regulating immune‐associated diseases and chronic inflammatory disorders. Here, we found that lncRNAs involve in the pathogenesis of psoriasis through integrative analysis of RNA‐seq data sets from a psoriasis cohort. Then, lncRNA‐protein‐coding genes (PCGs) co‐expression network analysis demonstrated that lncRNAs extensively interact with IFN‐γ signalling pathway‐associated genes. Further, we validated 3 lncRNAs associate with IFN‐γ signalling pathway activation upon IFN‐γ stimulated in HaCaT cells, and loss of function experiments indicate their functional roles in the activation of inflammatory cytokine genes. Additionally, microRNA target screening analysis showed that lncRNAs may regulate JAK/STAT pathway activity through complete endogenous RNA (ceRNA) mechanism. Further experimental validation of PRKCQ‐AS1/STAT1/miR‐545‐5p regulatory circuitry showed that lncRNAs regulate the expression of JAK/STAT signalling pathway genes through competing for miR‐545‐5p. In summary, our results demonstrated that dysregulation of lncRNA‐JAK/STAT pathway axis promotes the inflammation level in psoriasis and thus provide potential therapeutic targets for psoriasis treatments.

Psoriasis is a chronic inflammatory skin disease. Although miRNAs are reported to be associated with the pathogenesis of psoriasis, the contribution of individual microRNAs toward psoriasis remains unclear. The miR-17-92 cluster regulates cell growth and immune functions that are associated with psoriasis. miR-17-3p is a member of miR-17-92 cluster; however, its role in dermatological diseases remains unclear. Our study aims at investigating the effects of miR-17-3p and its potential target gene on keratinocytes proliferation and secretion of pro-inflammatory cytokine and their involvement in psoriasis. Initially, we found that miR-17-3p was upregulated in psoriatic skin lesions, and bioinformatic analyses suggested that CTR9 is likely to be a target gene of miR-17-3p. Quantitative reverse-transcriptase PCR and immunohistochemical analysis revealed that CTR9 expression was downregulated in psoriatic lesions. Using dual-luciferase reporter assays, we identified CTR9 as a direct target of miR-17-3p. Further functional experiments demonstrated that miR-17-3p promoted the proliferation and pro-inflammatory cytokine secretion of keratinocytes, whereas CTR9 exerted the opposite effects. Gain-of-function studies confirmed that CTR9 suppression partially accounted for the effects of miR-17-3p in keratinocytes. Furthermore, Western blot revealed that miR-17-3p activates the downstream STAT3 signaling pathway while CTR9 inactivates the STAT3 signaling pathway. Together, these findings indicate that miR-17-3p regulates keratinocyte proliferation and pro-inflammatory cytokine secretion partially by targeting the CTR9, which inactivates the downstream STAT3 protein, implying that miR-17-3p might be a novel therapeutic target for psoriasis.

An 80-year-old women complained of painful erythema, papules, nodules on her right wrist for 9 months. Granuloma and inflammatory infiltrates with septate fungal hyphae were observed in pathological sections. Growth of demaciatious fungus on SDA was confirmed to be Exophiala spinifera by microscopic appearance and ITS rDNA sequencing. The diagnosis of phaeohyphomycosis due to E. spinifera was established. The patient had a poor response to oral itraconazole (200 mg/d) combining with terbinafine (250 mg/d) for 6 weeks. Then, following three courses of ALA-PDT, used as adjuvant therapy, skin lesions greatly improved and remained stable after 3 months follow-up. The case suggests that ALA-PDT is an effective adjuvant treatment option for patients with recalcitrant local subcutaneous fungal infection.

Graphene has some outstanding properties in the photoelectric field, especially ultra fast response and broad spectrum absorption, which have led to strong attraction on graphene photodetector. However, the photoresponsivity of pure graphene device is below 10 mA W−1. It would limit the application of graphene photodetector. Here, we design a metamaterial structure with a broadband high absorption spectrum. And by integrating it into the graphene photodetector, the high photoresponsivity of a pure graphene photodetector in a broadband range could be acquired. The photoresponsivity of photodetector can achieve nearly 200 mA W−1, which is two orders higher than the one of pure monolayer graphene photodetector. Besides, the photodetector also keeps the broadband photoresponse. The hot carriers can be generated by coupling of multiple resonances and effectively transported to graphene with the advantage of ultrathin metal film. Based on this work, more potential applications of graphene photodetector could be developed in some related fields.