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Objective To investigate the efficacy and safety of Sonidegib for basal cell carcinoma. Methods Clinical data and skin histology were analyzed in a patient with ulcerated brown plaque on the nasal dorsum. After the diagnosis of basal cell carcinoma, patient was orally given a Hedgehog pathway inhibitor, Sonidegib. Results The patient was diagnosed with basal cell carcinoma. After the treatment with Sonidegib, the skin lesions became flat and ulcers were healed, without the development of new ulcers. Prior to the treatment, patient's liver and muscle enzymes were normal. Following one-week treatment with Sonidegib, the patient experienced muscle weakness, loss of appetite, vomiting, fatigue, and drowsiness, with an EGOG level of 3. After 4 weeks of treatment, the liver enzymes and serum CK were 2.5 times over normal levels. Sonidegib was discontinued at week 6 due to his intolerance of side effects. Then the patient was given the Mohs surgery and skin grafting. Conclusions Sonidegib can induce liver damage and musculoskeletal reactions. Adverse reactions should be dynamically monitored in clinical use of this drug. If the tumor is large or direct surgical removal may cause severe trauma, neoadjuvant therapy can be beneficial. In clinic, drugs can be intermittently administered according to patients' tolerance to improve tolerance and adherence.

Objective To investigate the target of indirubin in psoriasis, and to elucidate the possible effect of indirubin on psoriasis through MAPK14. Methods The GSE30999 and GSE78097 psoriasis datasets downloaded from the Gene Expression Omnibus (GEO) database were used as training and validation sets, respectively. The differentially expressed genes were screened, and their biological functions and pathways were analyzed. Intersections with indirubin target genes were used to obtain differentially expressed indirubin target genes. Meanwhile gene correlation was analyzed and differential gene expression was verified. LASSO and Cox regression model were used to screen the best target genes for indirubin. Molecular docking of indirubin was performed to analyze the structural relationship. Results A total of 8 indirubin target genes were found in the GSE30999 dataset, which were differentially expressed compared with the control group. Seven genes had high diagnostic value (AUC>0.8), and one gene had low diagnostic value (AUC>0.6). GO and KEGG enrichment analyses showed that the eight indirubin target genes were mainly related to cell aging, chemical carcinogenic receptor activation, lipid and atherosclerosis, acute myeloid leukemia, and AGE-RAGE signaling pathways in diabetic complications. The best target gene of indirubin, MAPK14 gene, was screened by LASSO and Cox regression model. Molecular docking suggested that indirubin was tightly bound to MAPK14. Conclusion Indirubin may be involved in the regulation of the pathogenesis and treatment of psoriasis through MAPK14.

Objective To evaluate the efficacy and safety of Spesolimab in the treatment of generalized pustular psoriasis(GPP). Methods A 30 years old female with GPP was intravenously given 900 mg of Spesolimab once. The safety and the changes in modified generalized pustular psoriasis area severity index (GPPASI) and generalized pustular psoriasis physician global assessment (GPPGA) were evaluated. Results After 1 week of the treatment, the GPPGA reached 2. After 2 months of the treatment, pustules almost completely subsided and both GPPASI and GPPGA reached 1. During the treatment, the patient developed anaphylactic adverse reactions, which were improved following the injection of betamethasone, antihistamine and symptomatic therapy. Conclusion Spesolimab is an effective and safe agent for the treatment of generalized pustular psoriasis.

Objective To investigate the expression and regulatory mechanism of PTPN2 in psoriasis, and to analyze the effects of PTPN2 on psoriasis related immunity in order to determine whether PTPN2 can be used as a potential therapeutic target for psoriasis. Methods R language (3.6.3 version) was used to determine the difference in expression levels of PTPN2 between psoriatic patients and controls, and the receiver operating characteristic (ROC) curve of PTPN2. The Gene Enrichment Analysis software (GSEA) and the Protein Interaction Analysis Database (STRING) were used to determine enrichment pathway of PTPN2 in the psoriasis dataset, and the interaction network of PTPN2 co-expressed genes. The distribution and expression of immune cells in psoriasis datasets were analyzed with CIBERSORT software. The differential expression of immune response pathways and immune response gene sets in psoriasis and their correlation with PTPN2 were analyzed using R language (version 3.6.3). Results PTPN2 mRNA was highly expressed in psoriatic lesions. Immune infiltrating cells, immune response pathways, and immune response gene sets were abnormal in psoriatic lesions. PTPN2 was associated with some immune infiltrating cells, immune response pathways, and immune response gene sets in psoriasis. Conclusions PTPN2 mRNA is highly expressed in psoriatic lesions, and may participate in the occurrence and development of psoriasis by regulating the immune microenvironment.

Objectives Childhood cancer survivors may experience complex health issues during transition and long-term follow-up (LTFU); therefore, high-quality healthcare is warranted. Care coordination is one of the essential concepts in advanced healthcare. Care coordination models vary among childhood cancer survivors in transition and LTFU. This study aimed to identify care coordination models for childhood cancer survivors in transition and LTFU and synthesise essential components of the models.Design This scoping review was guided by the methodological framework from Arksey and O’Malley and was reported with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A systematic literature search was conducted on six databases using possible combinations of terms relevant to childhood cancer survivors, transition/LTFU and care coordination model. Data were analysed by descriptive and content analysis.Data sources The literature search was first conducted in May 2023 and updated in May 2024. Six databases including Medline, PubMed, Embase, Web of Science, CINAHL and Cochrane Library were searched; meanwhile, a hand search was also conducted.Eligibility criteria for selecting studies Studies relevant to describing any models, interventions or strategies about care coordination of transition or LTFU healthcare services among childhood cancer survivors were included.Data extraction and synthesis Two reviewers independently screened and included studies. Basic information as well as care coordination model-related data in the included studies were extracted. Descriptive summary and content analysis were used for data analysis.Results In the 20 545 citations generated by the search strategy, seven studies were identified. The critical determinants of the models in the included studies were the collaboration of the multidisciplinary team, integration of the navigator role and the provision of patient-centred, family-involved, needs-oriented clinical services. The main functions of the models included risk screening and management, primary care-based services, psychosocial support, health education and counselling, and financial assistance. Models of care coordination were evaluated at patient and clinical levels. Based on this review, core concepts of successful care coordination models for childhood cancer survivors in transition or LTFU were synthesised and proposed as the ‘3 I’ framework: individualisation, interaction and integration.Conclusion This scoping review summarised core elements of care coordination models for childhood cancer survivors’ transition and LTFU. A proposed conceptual framework to support and guide the development of care coordination strategies for childhood cancer survivors’ transition and LTFU care was developed. Future research is needed to test the proposed model and develop appropriate care coordination strategies for providing high-quality healthcare for childhood cancer survivors’ transition and LTFU.

Objective To report a case of hemophagocytic lymphohistiocytosis syndrome (HLH) secondary to systemic hydroa vacciniforme lymphoproliferative disorder (systemic HVLPD) and review relevant literature, in order to improve understanding of the disease. Methods Clinical data of the case, laboratory examination, histopathology, immunohistochemistry, TCR gene rearrangement, and whole exon gene sequencing were collected for analyses. Results A 19 years old man was admitted to the hospital due to generalized papules, blisters, necrotic scabs and fever for 7 months. The clinical manifestations included hydroa vacciniforme-like rashes, lymphadenopathy, splenomegaly, pancytopenia, hypertriglyceridemia, decreased NK cell activity, high levels of sIL-2r, positive for VCA-IgA and EA-IgA, and elevated EBV DNA load. The whole exon sequencing did not show pathogenic gene mutations. Histopathological changes in the skin lesions included liquefaction degeneration of epidermal and follicular basal cells, pigmentary incontinence, lymphocytic infiltrates of the epidermis and follicular epithelium, perivascular and perifollicular infiltrates of lymphocytes and eosinophils in the dermis, extravasation of erythrocytes, as well as focal infiltrates of atypical lymphoid cells around appendages and small blood vessels. Pathologic mitosis was visible. Immunohistochemistry showed CD3 (+), CD5 (+), CD20 (individual+), CD30 (small patch+), CD79a (individual+), CD4 (+), CD7 (+), CD8 (+), TIA-1 (+), CD56 (scattered lymphocyte+), ≈50% of Ki-67(+), and in situ hybridization EBER (+). TCRβ gene monoclonal rearrangements were detected. According to the results of clinical and auxiliary examination, patient was diagnosed with HLH secondary to systemic HVLPD. After 8 months of follow-up, the patient passed away while waiting for transplantation of allogeneic hematopoietic stem cells. Conclusions Systemic HVLPD is rare and requires vigilance for the development of secondary hemophagocytic syndrome. The awareness of hemophagocytic syndrome should be improved to avoid possible misdiagnosis and delayed treatment.

Objective To report a case of hereditary skin disease mainly characterized by burning pain of the lower legs and feet, accompanied by flush and elevated skin temperature, and to identify the pathogenic genes and mutation sites in order to explore effective treatment methods. Methods The clinical data of the case were collected and peripheral blood was taken from the patient and relatives to extract genomic DNA. Next-generation sequencing of hereditary skin disease genes was performed, and suspected pathogenic mutations were verified with Sanger sequencing. The patient was treated with aspirin for anti-inflammation, rizatriptan benzoate tablet, mexiletine hydrochloride, carbamazepine, local injection of botulinum toxin analgesia, topical compound polymyxin B ointment and cooling therapy. Results A heterozygous mutation of SCN9A:NM_002977.3:c.688+142G>A or SCN9A:ENST00000375387.4:c.626G>A was detected in the patient's peripheral blood genomic DNA. The same mutation was found in the patient's sister, an uncle and a cousin. Based on the pathogenic gene and clinical manifestations, the patient was diagnosed with primary erythromelalgia (PEM). After the treatment, the pain was significantly alleviated. Conclusions The intron mutation of NM_002977.3:c.688+142G>A or missense mutation c.626G>A(p.Gly209Asp) of the SCN9A gene is the cause of PEM in this case. Combination therapy of aspirin, rizatriptan benzoate, mexiletine hydrochloride, carbamazepine and local treatment can effectively control the symptoms of PEM, reduce the frequency of acute attacks and improve the prognosis.

Abstract Acute myeloid leukemia (AML), a prevalent form of leukemia in adults, is often characterized by low response rates to chemotherapy, high recurrence rates, and unfavorable prognosis. A critical barrier in managing refractory or recurrent AML is the resistance to chemotherapy. Increasing evidence indicates that tumor cell metabolism plays a crucial role in AML progression, survival, metastasis, and treatment resistance. Autophagy, an essential regulator of cellular energy metabolism, is increasingly recognized for its role in the metabolic reprogramming of AML. Autophagy sustains leukemia cells during chemotherapy by not only providing energy but also facilitating rapid proliferation through the supply of essential components such as amino acids and nucleotides. Conversely, the metabolic state of AML cells can influence the activity of autophagy. Their mutual coordination helps maintain intrinsic cellular homeostasis, which is a significant contributor to chemotherapy resistance in leukemia cells. This review explores the recent advancements in understanding the interaction between autophagy and metabolism in AML cells, emphasizing their roles in cell survival and drug resistance. A comprehensive understanding of the interplay between autophagy and leukemia cell metabolism can shed light on leukemia cell survival strategies, particularly under adverse conditions such as chemotherapy. This insight may also pave the way for innovative targeted treatment strategies.

Synthetic aperture LiDAR can generate point cloud data, which is widely used in 3-D scene reconstruction. However, existing point cloud object recognition methods are vulnerable to adversarial attacks, and such attacks are difficult to transfer to the physical world. Even if adversarial perturbations are added to physical objects, they are easily detectable by other sensors. Our proposed method includes two modules, R-D and D-R, which generate more concealed adversarial point cloud samples by modifying digital and physical features. The R-D module maps real-world entities to point cloud data in the digital world and generates adversarial samples by modifying signal amplitude values. The D-R module constructs adversarial objects by modifying the surface diffuse reflectance of the target object based on ray tracing and correspondences between digital and physical features. Our method is evaluated through experiments on attack effectiveness, robustness after subsampling and transferability, demonstrating its effectiveness, and achieving new state-of-the-art performance.

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Background: Anterior gradient 2 (AGR2) is highly enriched in several malignant tumors and can boost tumor metastasis. Whereas, AGR2 role in colorectal cancer (CRC) is not clear. Methods: AGR2 expression in the GEPIA database was studied, and the results were confirmed by Western blot in CRC cell lines (SW480, SW620, and HT-29). The impact of AGR2 on the multiplication, migration, invasion and EMT of CRC cells were studied by CCK-8 assay, as well as clone formation, wound healing and transwell assays. The protein concent related to the AKT/β-catenin signaling pathway were accessed via Western blot. Results: AGR2 concent in CRC tissues was notablely boosted versus normal colorectal tissues. Exogenous AGR2 boosted the multiplication of CRC cells. In addition, exogenous AGR2 induced EMT, which demonstrated that ZEB1, N-cadherin, Vimentin, Slug, Snail protein concent boosted and E-cadherin protein abated in CRC cells. In terms of mechanism, exogenous AGR2 upgulated p-AKT/AKT, p-GSK3β/GSK3β and β-catenin concent. Exogenous AGR2 combined with AKT agonist IGF- Ⅰ can further enhance the multiplication, migration and invasion of CRC cells. Conclusion: Exogenous AGR2 enhances the multiplication of CRC cells and induces EMT process, the mechanism of which is related to AKT/β-catenin signal pathway.

Objective To investigate the mechanisms of nicotinamide phosphoribosyl transferase (NAMPT) in the pathogenesis of psoriasis and to elucidate the effect of NAMPT on the nicotinamide adenine dinucleotide (NAD+) metabolic pathway in psoriasis. Methods Mitophagy gene and psoriasis microarray datasets were downloaded from the human autophagy gene database and GEO database to screen differentially expressed genes (DEGs) of mitophagy. Validation and assessment were performed by differential expression and receiver operating characteristic (ROC) curve analysis. LASSO and COX regression models were used to screen signature genes. Gene correlation and functional analysis were performed using Pearson and gene enrichment analysis (GSEA). Results A total of 16 differentially expressed mitophagy genes were identified in psoriasis, which all were highly expressed in psoriasis with high diagnostic value. The DEGs of mitophagy were mainly associated with NOD-like receptor signaling pathway, autophagy-animal, influenza A, chemo carcinogenic-receptor activation and lipid/atherosclerotic pathways. NAMPT was identified as a signature gene of psoriasis, mainly associated with the proteasome, pyrimidine metabolism, ubiquitin-mediated proteolysis, DNA replication, antigen processing and presentation, aminoacyl tRNA biosynthesis, cytoplasmic DNA sensing pathway, oocyte meiosis, homologous recombination and TOLL-like receptor signaling pathway. In psoriasis, NAD metabolic pathways were activated and positively correlated with NAMPT. In the NAD+ metabolic pathway, expression levels of BST1 were low and negatively correlated with NAMPT. In contrast, expression levels of PARP9 and PNP were high and positively correlated with NAMPT. Conclusions In psoriasis, NAMPT is highly expressed and NAD+ metabolic pathway is activated. Expression levels of NAMPT are positively correlated with the activity of NAD+ metabolic pathway. NAMPT may be involved in the pathogenesis of psoriasis through BST1, PARP9 and PNP in the NAD+ metabolic pathway.

Most toughening methods for epoxy resins are usually used at the expense of other properties. Some polyhedral oligomeric silsesquioxanes (POSSs) with both a rigid Si-O-Si structure and flexible organic chain segments could be expected to be effective toughening agents. In this study, three reactive polyhedral oligomeric silsesquioxanes with a thiol group (OMPPS), a carboxyl group (OCOPS), and an epoxy group (OGCPS) were synthesized and characterized. They were utilized as modifiers to toughen 3-(oxiran-2-ylmethoxy)-N,N-bis(oxiran-2-ylmethyl)aniline (AFG-90MH)/4,4′-methylenebis(2-ethylaniline) (MOEA) (epoxy resin) with different molar ratios to obtain hybrid resins named OMPPS-EP-i, OCOPS-EP-j, and OGCPS-EP-k. The effects of the amount of modifier added and the length of the organic chain on the cage structure on various properties of the hybrid resins were investigated. The results show that all three modifiers show good compatibility with the epoxy resin. The hybrid resins have a low viscosity at 45~85 °C and can be cured at a low temperature (110 °C). The cured hybrid resins display improved toughness. Typically, the critical stress intensity factor (KIC) and impact strength of OGCPS-EP-0.6-C are 2.54 MPa∙m−1/2 and 19.33 kJ∙m−2, respectively, which increased by 58.75% and 22.48% compared with the pristine epoxy resin, respectively. In addition, the glass transition temperature and flexural strength of the hybrid resins are basically unchanged.

Abstract Purpose Malignant melanoma is a tumor generated from the basal melanocytes of human epidermis. Primary malignant melanoma of the cervix (PMMC) is derived from cervical melanocytes. It is an uncommon disease, mostly occurring in perimenopausal women. PMMC has a bad prognosis and lacks a defined protocol or treatment standards. The aim of this study was to analyze the impact of different surgical procedures and different adjuvant treatment modalities on their prognosis and to find risk factors for their prognosis by integrating published case report data based on the Chinese population. Methods and Results This study included 165 patients with PMMC in the Chinese population. We used the Kaplan‐Meier method to build the survival curve, and the log‐rank test to examine the variations among the subgroups. Prognostic factors were examined utilizing the Cox proportional hazards regression model. We found that patients who underwent radical hysterectomy‐based surgery, those who underwent lymphadenectomy, and those who underwent other treatments in addition to surgery had significantly better survival rates. The overall analysis, showed that age, and FIGO Stage II, III, and IV, increased the risk of death. Moreover, radical hysterectomy (RH), total hysterectomy (TAH), lymphadenectomy, and adjuvant therapy were correlated with a decreased mortality risk. Conclusion After summarizing the current data, we recommend radical hysterectomy, and lymphadenectomy treatment for patients with PMMC. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis; therefore patient‐specific treatment options need to be further discussed.

With the increasing construction of undersea tunnels in seismic-prone areas, accurately assessing their response to seismic conditions is crucial. To grasp the dynamic response of undersea tunnel structures to seismic waves, the shaking table test of water–sea–sea submarine tunnel is designed and carried out based on the methods of orthogonal design and fuzzy method. A comprehensive time-domain model is developed to capture the nonlinear dynamic interaction of ocean engineering structures, taking into account seismic waves, seawater, and saturated soil. The research results show that as the burial depth at each measurement point of the submarine tunnel increases, the acceleration response decreases and the horizontal displacement relative to the seabed surface increases. Comparing test and finite element simulation results reveals that under seismic loading, the strain distribution pattern of the tunnel section is mainly in the arch shoulder, waist, and foot with larger strain peaks, whereas the strain peaks at the arch top and the superelevation arch are smaller. Simultaneously, doubling the water pressure induces a slight increase in the overall strain response peak of the tunnel, with an indistinct relative displacement change rule. When a vertically polarized shear wave (SV wave) is vertically incident, different dynamic response indices will have different trends with the change in water level. This study may provide a reference for shaking table tests for saturated soil–submarine tunnels at complex sites.

We report a case of eosinophilic fasciitis. A 58-year-old man complained of muscle weakness and stiffness, and joint pain of the limbs for 11 months. Dermatological examination revealed groove sign, which became more prominent when raising the arm. The skin of the forearms and calves was waxy appearance and tight. Muscle weakness and pain were apparent. The laboratory examination showed the absolute eosinophil count was 1.51×109/L in December, 2020, and 0.45 ×109/L in June, 2021. The erythrocyte sedimentation rate was 104 mm/h. Other test results were immunoglobulin G (IgG) 32.7 g/L, C3 0.881 g/L, gamma globulin 36.5%, and the anti-Scl-70 antibody (negative). The histopathology of the lesion on the right forearm was manifested by epidermal atrophy, collagen thickening in the fascia, hyaline degeneration, perivascular infiltration of plasma cells, lymphocytes, and eosinophils, remarkable reduction in elastic fibers in the fascia, and alcian blue stain(+). Patient was diagnosed with eosinophilic fasciitis. The patient refused the treatment with baricitinib and was without follow up.

Abstract The internal tandem duplication of the juxtamembrane domain of the FMS-like tyrosine kinase 3 (FLT3-ITD) is the most common genetic change in acute myeloid leukemia (AML), and about 30% of all AMLs harbor a FLT3-ITD mutation. Even though FLT3 inhibitors have displayed encouraging effects in FLT3-ITD-mutated AML, the extent of the clinical response to these compounds is cut short due to the rapid development of drug resistance. Evidence has shown that FLT3-ITD triggered activation of oxidative stress signaling may exert a pivotal role in drug resistance. The downstream pathways of FLT3-ITD, including STAT5, PI3K/AKT, and RAS/MAPK, are considered to be major oxidative stress signaling pathways. These downstream pathways can inhibit apoptosis and promote proliferation and survival by regulating apoptosis-related genes and promoting the generation of reactive oxygen species (ROS) through NADPH oxidase (NOX) or other mechanisms. Appropriate levels of ROS may promote proliferation, but high levels of ROS can lead to oxidative damage to the DNA and increase genomic instability. In addition, post-translational modifications of FLT3-ITD and changes in its subcellular localization can affect downstream signaling which may also be one of the mechanisms leading to drug resistance. In this review, we summarized the research progress on NOX mediated oxidative stress signaling and its relationship with drug resistance in FLT3-ITD AML, and discuss the possible new targets in FLT3-ITD signal blocking to reverse drug resistance in FLT3-ITD-mutated AML.

Objective Using bioinformatic technique to identify key genes and pathways involved in the pathogenesis of pemphigus foliaceus (PF), in order to elucidate the pathogenesis of PF. Methods Gene microarray dataset GSE53873 of peripheral blood CD4+ T cells from PF patients was obtained from Gene Expression Omnibus database, and various bioinformatics methods such as Limma difference analysis, gene function and pathway enrichment analysis, and protein-protein interaction network analysis were integrated to determine the key genes and pathways associated with PF. Results A total of 121 significantly upregulated genes and 48 significantly downregulated genes were identified in PF patients compared with healthy controls. The differentially expressed genes in PF patients were involved in multiple functions such as T cell differentiation, T cell activation, leukocyte differentiation and metabolism. CXCL10 and OAS1 were identified as key genes in the pathogenesis of PF. Receiver operating characteristic (ROC) results suggested that CXCL10 (AUC=0.86) and OAS1 (AUC=0.86) had high diagnostic efficacy for PF. Gene function and pathway enrichment analysis indicated that CXCL10 was mainly associated with TOLL-like receptor signaling pathway, COVID-19 infection, and cytokine interaction, while OSA1 was mainly associated with viral infection and type I interferon signaling pathway. Conclusions CXCL10 and OAS1 are the key genes associated with PF. The pathogenesis of pemphigus is associated with pathways such as T cell differentiation and activation, leukocyte differentiation and metabolism.

The human gut microbiota refers to the collective assembly of microorganisms inhabiting and colonizing the gastrointestinal tract, including bacteria, archaea, and eukarya.1 This intricate microbial ecosystem exists in a symbiotic relationship with the host, with trillions of microorganisms playing key roles in maintaining human health.2 Firmicutes and Bacteroidetes represent the predominant bacterial phyla that form the intestinal microbiome.2 The gut microbiota has developed adaptive mechanisms to promote its survival within the gastrointestinal tract. Development of the intestinal microbiome has been depicted and seems to be influenced by a variety of factors, e.g., mode of delivery, diet during infancy and adulthood, illnesses, and antibiotic treatment causing variation in the composition of the microbiota.3 Before the age of three, children’s intestinal microbiome already resembles the gut microbiota of adult individuals in terms of functional capabilities, diversity, and composition.4 The gut microbiota offers numerous benefits to the host as its metabolic activity is responsible for the generation of short-chain fatty acids which are a source of energy for the host, and for the fermentation of carbohydrates leading to the synthesis of oxalates, reducing the risk of oxalate stones in the kidney.5 In addition, the microbiota promotes lipid metabolism, vitamin synthesis, polyphenol breakdown, drug metabolism, immunomodulation, which offers immune-protection, and maintains the structural integrity of the gastrointestinal tract.3 Therefore, the gut microbiota represents an intricate microbial ecosystem that plays a critical role in maintaining human health. Continue...

Geographical differences are conspicuous in lung cancer, and the distinct molecular features of lung tumor between Western patients and Asian patients have been demonstrated. However, the etiology of non-small-cell lung cancer (NSCLC) and the distribution of associated molecular aberrations in China have not been fully elucidated. The mutational profiles of 12 lung cancer-related genes were investigated in 85 patients from eastern China and 88 patients from southern China who had been histologically confirmed NSCLC. Overall, 93.6% (162/173) of tumor samples harbored at least one somatic alteration. The most frequently mutated genes were TP53 (56.1%), EGFR (50.3%), and KRAS (14.5%). We found that EGFR mutated much more frequently (60.0% vs 40.9%, P = 0.012) and TP53 mutations had significantly lower incidence (47.1% vs 64.8%, P = 0.019) in eastern cohort than that in southern cohort. Mutational signature analysis revealed a region-related mutagenesis mechanism characterized by a high prevalence of C to T transitions mainly occurring at CpG dinucleotides in southern patients. This study reveals the difference in the mutational features between NSCLC patients in eastern and southern China. The distinct patterns of gene mutation could provide clues for the mechanism of carcinogenesis of lung cancer, offering opportunities to stratify patients into optimal treatment plans based on genomic profiles.

Objective To investigate the roles of cytokines, IL-36γ and IL-38, in the inflammatory response in psoriasis vulgaris. Methods Both serum and peripheral blood mononuclear cells (PBMC) were collected from 29 patients with psoriasis vulgaris (PV) and 19 healthy controls. PV group was divided into mild to moderate group (n=14) and severe group (n=15) according to psoriasis area and severity index (PASI). In addition, serum and PBMC were collected from 12 PV patients before and after the treatment with IL-17A monoclonal antibody (IL-17A mAb). Serum levels of IL-36γ and IL-38 were measured using ELISA, and the relative expression levels of IL-36γ and IL-38 mRNA in PBMC were determined using RT-quantitative real-time PCR (RT-qPCR). Moreover, human immortalized keratinocytes (HaCaT) cocultured with IL-17A were sampled at different time points to measure expression levels of IL-36γ and IL-38 mRNA. Results Serum IL-36γ levels were significantly higher in patients with either mild to moderate or severe psoriasis than in healthy controls (t=12.27 and 16.45, respectively, P

Abstract 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.

The Pharmaceutics Editorial Office retracts the article, “A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy” [...]

Context The effects of Rhodiola rosea L. (Crassulaceae) polysaccharides (RRPs) on haematopoiesis are poorly understood.Objective To determine the effects of RRPs on haematopoiesis in mice with aplastic anaemia.Materials and methods Aplastic anaemia was induced in Kunming mice by 60Coγ (2.0 Gy) irradiation and cyclophosphamide administration (50 mg/kg/day for 3 consecutive days; intraperitoneal injection). The in vivo effects of RRPs (10, 20, and 40 mg/kg; intraperitoneal injection) on haematopoiesis were analyzed using peripheral blood tests, histopathological examination of haematopoietic tissues, culture of haematopoietic progenitors and bone marrow stromal cells (BMSCs), and Western blotting of Fas and Fas ligand (FasL). The in vitro effects of RRPs on bone-marrow haematopoietic progenitors and BMSCs were also evaluated.Results Compared to anaemic controls, high-dose RRPs (40 mg/kg) significantly increased red blood cells (8.21 ± 0.57835 versus 6.13 ± 1.34623 × 1012/L), white blood cells (5.11 ± 1.6141 versus l.54 ± 1.1539 × 109/L), and BMSCs (10.33 ± 1.5542 versus 5.87 ± 3.1567 × 1012/L) in mice with aplastic anaemia (all p

Objective To detect the expression and localization of Sprouty 2, E-cadherin (E-cad) and Ki-67 in skin tissue of squamous cell carcinoma (CSCC), and to analyze the correlation of Sprouty 2 with E-cad and Ki-67. Methods From March 2018 to July 2018, cancerous tissues (squamous cell carcinoma group), paracancerous tissues (paracancer group), normal skin tissues (case control group) were collected from 15 patients with cephalic and facial CSCC and 10 cases of control normal skin specimens (healthy control group) at Dermatology Hospital of Southern Medical University. Expression and localization of Sprouty 2, E-cad and Ki-67 were detected by qRT-PCR, Western blot and immunohistochemical staining. Results Immunohistochemistry showed that Sprouty 2 was expressed in the keratinocytes and cytoplasm of the whole epidermal layer in all groups. E-cad was expressed in the cell membrane of keratinocytes of all epidermal layers in all groups. Ki-67 was localized in keratinocytes of the basal layer and lower spinous layer in all groups. qRT-PCR and Western blot showed that the mRNA and protein expression in squamous cell carcinoma group were lower than that in paracancer group, case control group and healthy control group (mRNA 0.03±0.03 vs. 0.28±0.36,0.92±0.60, 1.12±0.56; protein 0.68±0.47 vs 1.40±0.72, 1.59±0.86, 1.71±1.28, all P

Abstract 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.

We report a case of skin damage due to overdose methotrexate poisoning. A 74-year-old woman presented with erythema and desquamation of trunk and limbs accompanied with pain for 8 days. Before admission, MTX 5 mg/d was taken orally for 10 days, and the accumulative dose was 50 mg. On the third day of taking the medicine, erythema and desquamation appeared all over the body. Dermatology examination revealed that oral mucosal erosion and skin of trunk and limbs with erythema diffuse distributed, and erosion oozing on the surface of skin desquamated and some areas. Laboratory examinations revealed that the decreased number of leukocyte and platelets and elevated transaminase. The case was diagnosed with methotrexate poisoning. The patient was treated with Leucovorin, methylprednisolone, hydration, alkalized urine, recombinant human granulocyte stimulating factor, recombinant human thrombopoietin, topical medicine, and other symptomatic and supportive treatments. After 2-week treatments, the patient recovered.

The increasing evidence showed that psoriasis and inflammatory bowel disease are now considered as chronic systemic inflammatory diseases, and they are comorbidities for each other. Due to multiply overlapping pathophysiological mechanisms, drugs targeting to their common pathways have become hot spots in the current treatment of these two comorbidities. This review summarizes the common pathways involved in psoriasis and inflammatory bowel disease, including extracellular tumor necrosis factor, IL-23, IL-17 signaling pathways, as well as intracellular JAK-STAT pathway, cAMP signaling pathway, and ROR-γT/Th17 axis. Additional, this paper also briefly summarizes the drugs targeting to these common pathways. Altogether, the paper can provide some ideas for clinical treatment of these two comorbidities.

Background: It is necessary to determine the diabetes knowledge level among non-endocrinology nurses in primary care hospitals to develop continuing education strategies. Method: A questionnaire survey was conducted among 6819 non-endocrinology nurses in 70 primary hospitals in the Guangxi Zhuang Autonomous Region to assess their diabetes knowledge level and training needs. Factors affecting knowledge level were analyzed using multiple linear regression models. Results: Diabetes knowledge was low, particularly for diabetes monitoring. Knowledge was higher in nurses who had in-service education and training in diabetes; most believed that training was necessary and hoped to improve their ability to care for diabetic patients. The most suitable training method was considered to be each nurse was taught by an assigned person after centralized specialized education and training. Conclusion: Non-endocrinology nurses in primary care hospitals lack knowledge of diabetes and have a strong need for training. Systematic training is required to ensure that patients receive high-quality and comprehensive care.

Abstract 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.

BackgroundIn secondary spinal cord injury (SCI), the immune microenvironment of the injured spinal cord plays an important role in spinal regeneration. Among the immune microenvironment components, macrophages/microglia play a dual role of pro-inflammation and anti-inflammation in the subacute stage of SCI. Therefore, discovering the immune hub genes and targeted therapeutic drugs of macrophages/microglia after SCI has crucial implications in neuroregeneration. This study aimed to identify immune hub genes and targeted therapeutic drugs for the subacute phase of SCI.MethodsBulk RNA sequencing (bulk-RNA seq) datasets (GSE5296 and GSE47681) and single-cell RNA sequencing (scRNA-seq) dataset (GSE189070) were obtained from the Gene Expression Omnibus database. In the bulk RNA-seq, the R package ‘limma,’ ‘WGCNA,’ and ‘CIBERSORT’ were used to jointly screen key immune genes. Subsequently, the R package ‘Seurat’ and the R package ‘celldex’ were used to divide and annotate the cell clusters, respectively. After using the Autodock software to dock immune hub genes and drugs that may be combined, the effectiveness of the drug was verified using an in vivo experiment with the T9 SCI mouse model.ResultsIn the bulk-RNA seq, B2m, Itgb5, and Vav1 were identified as immune hub genes. Ten cell clusters were identified in scRNA-seq, and B2m and Itgb5 were mainly located in the microglia, while Vav1 was mainly located in macrophages. Molecular docking results showed that the proteins corresponding to these immune genes could accurately bind to decitabine. In decitabine-treated mice, the pro-inflammatory factor (TNF-α, IL-1β) levels were decreased while anti-inflammatory factor (IL-4, IL-10) levels were increased at 2 weeks post-SCI, and macrophages/microglia transformed from M1 to M2. At 6 weeks post-SCI, the neurological function score and electromyography of the decitabine treatment group were also improved.ConclusionIn the subacute phase of SCI, B2m, Itgb5, and Vav1 in macrophages/microglia may be key therapeutic targets to promote nerve regeneration. In addition, low-dose decitabine may promote spinal cord regeneration by regulating the polarization state of macrophages/microglia.

Abstract 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.

Objective To explore the function and mechanism of lncRNA on the cell cycles in psoriasis. Methods We first identified the differentially expressed genes through integrative analysis of RNA-seq datasets from a psoriasis cohort. Then KEGG analysis was performed to identify the key signaling pathways in psoriasis. WGCNA was used to construct the lncRNA-protein coding genes (PCGs) co-expression network. A specific siRNA was used to knockdown LINC01206 in HaCaT keratinocytes and the cell cycle progression was detected by flow cytometry. Results Integrative analysis of RNA-seq datasets from the psoriasis cohort demonstrated a dysregulation of the cell cycle pathway in psoriasis. Moreover, lncRNA-protein coding gene (PCGs) co-expression analysis showed that LINC01206, LINC01269, LINC01215and LINC02159 interacted with the key factors CCNA2, CCNB1 and CCNE1, in cell cycle pathway to regulate the progress of psoriasis. Flow cytometry analysis showed that knockdown of LINC01206 induced cell cycle arrest at the G2/M phase. Conclusions Our results demonstrate the functional mechanism of lncRNAs in the cell cycle. LncRNA may be a therapeutic target for psoriasis.

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.

Polycationic vectors are a promising class of gene delivery systems. To improve delivery efficiency and reduce cytotoxicity, hydrophobic modification has been proposed as an effective way. Herein, we synthesized a class of terpolymer vectors with various hydrophobicities as well as multiple biodegradable disulfide bonds and cationic side chains. The chemical structure and hydrophobic modification ratio of polymers were characterized. The amphiphilic vectors were able to condense pDNA to form flexible and uniform nanoparticles with a size of 60–85 nm. The shielding effect of hydrophobic side chains led to a lower zeta potential and reduced cytotoxicity. The endocytosis efficiency of amphiphilic vectors was significantly increased and the endocytosis pathway shifted from mainly via the clathrin pathway to clathrin/caveolae/lipid raft co-mediated endocytosis. The amphiphilic vectors demonstrated significantly higher transfection efficiency. In addition, the hydrophobic structural domain of polymers could improve serum stability, alleviating the serum inhibition commonly seen in cationic polymers. Then, we tested the tumor-suppressor gene wtp53 delivered by the amphiphilic vectors in triple-negative breast cancer models both in vitro and in vivo. Tumor cell cycle arrest and apoptosis were triggered through the regulation of downstream cell cycle proteins and apoptosis proteins, inhibiting tumor growth with an excellent safety profile.

A case of epidermolytic palmoplantar keratosis caused by KRT9 mutation is reported. A 32-year-old Chinese man presented with a 30-year history of palmoplantar hyperkeratotic plaques. Dermatological examination showed the hyperkeratotic plaques on bilateral palms and soles, and rough thickened skin in gray-yellow color. The histopathology revealed markedly epidermolytic hyperkeratosis, acanthosis and vacuolar changes of the stratum granulosum. Whole-exome sequencing showed a exon mutation of KRT9 gene [c. 487C>T (p. Arg163Trp) ]. The patient was diagnosed as epidermolytic palmoplantar keratosis.

Objective: To investigate the effect of indirubin on the expression of proinflammatory cytokines in HaCaT cells, and to elucidate the mechanisms of Diqing ointment in the treatment of psoriasis. Methods: The human immortalized keratinocyte cell line, HaCaT cells, were used to observe the changes in the expression levels of IL-1β, IL-6, and TNF-α in HaCaT cells after treatment with different concentrations of indirubin. HaCaT cells were divided into 4 groups. The secretion levels of IL-1β, IL-6, and TNF-α in the culture supernatants were detected by enzyme-linked immunosorbent assay ELISA, and the expression levels of IL-1β, IL-6, and TNF-α mRNA were detected by real-time PCR (RT-qPCR). Results: Expression levels of both mRNA and protein of IL-1β, IL-6, and TNF-α were significantly and dose-dependently decreased after treatment with indirubin. Conclusion: Indirubin, the main component of Qingdai ointment, can lower expression levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in keratinocytes, leading to the improvements of psoriasis.

Objective: To explore the effect of YangxueJiedu decoction on IL-36 expression in a mouse model of imiquimod-induced psoriasis-like lesions. Methods: Eighteen mice were randomly divided into the control, model and experimental groups, with 6 mice per group. The psoriasis severity was assessed by PASI score. The expression levels of mRNA for IL-36α, IL-36β, IL-36γ, and IL-36Ra were measured by RT-qPCR. Expression levels of IL-36β protein were evaluated by both Western blot and immunohistochemistry. Results: PASI scores were significantly lower in experimental group than in the model group (1.17±0.37 vs 7.83±0.69, t=19.07, P

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.

In this paper, a sensitive biomimetic enzyme-linked immunoassay (BELISA) method based on an Au@Pt@Au composite nanozyme label was developed for histamine (HA) detection. A molecular imprinted polymer prepared directly on the 96-well plate served as a biomimetic antibody. A BELISA method was developed for HA standard solutions at concentrations ranging from 0.01 to 100.00 mg/L. Under optimal conditions, the novel BELISA method had a low limit of detection (0.069 mg/L) and high sensitivity (7.20 mg/L). The HA spiked in yellow rice wine and liqueur samples were detected by this BELISA method with the recoveries ranging from 84.28% to 108.82%. There was no significant difference of the results between the BELISA method and HPLC for the detection of HA in the red and white grape wine samples.

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.

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.

Abstract Background Shen-ling-bai-zhu-san (SLBZS) regulates inflammation and gut microbiota which are associated with Streptococcus pneumoniae (Spn)-induced pneumonia. So, we studied the therapeutic effect of SLBZS and evaluated whether gut microbiota is associated with the effects of SLBZS in improving Spn-induced pneumonia. Methods Spn-induced pneumonia NIH mice were treated by SLBZS and cefixime. A CT scan was performed and Myeloperoxidase (MPO) activity in lung homogenates was determined using the MPO Colorimetric Assay Kit. Inflammation levels in lung homogenates were measured using ELISA. Bacterial load was coated on a TSAII sheep blood agar. Intestinal gut microbiota information was analyzed according to sequencing libraries. Results SLBZS decreased bacterial load, reduced wet/dry weight ratio, inhibited myeloperoxidase activity, reduced the neutrophils count, and ameliorated lung injury. Furthermore, SLBZS inhibited interleukin (IL)-1β, IL-6, tumor necrosis factor-α, IL-2, IL-8, IL-12, and interferon-γ secretion and enhanced IL-10 secretion. These results suggest that SLBZS ameliorates lung injury in mice with Spn-induced pneumonia. Moreover, SLBZS reduced inflammatory cytokine levels in a concentration-dependent manner and increased gut microbiota abundance and diversity. After SLBZS treatment, bacteria such as Epsilonbacteraeota, Bacteroidetes, Actinobacteria, Proteobacteria, and Patescibacteria were significantly reduced, while Tenericutes and Firmicutes were significantly increased. Conclusion SLBZS ameliorates inflammation, lung injury, and gut microbiota in mice with S. pneumoniae-induced pneumonia.

Abstract Background Local recurrence is the main cause of death among patients with oral squamous cell carcinoma (OSCC). This study assessed near-infrared fluorescence (NIF) imaging and spectroscopy to monitor surgical margins intraoperatively for OSCC. Methods Cytological and animal experiments were first performed to confirm the feasibility of monitoring surgical margins with NIF imaging and spectroscopy. Then, 20 patients with OSCC were included in the clinical trials. At 6–8 h after 0.75 mg/kg indocyanine green (ICG) injection, all patients underwent surgery with NIF imaging. During the surgery, both NIF images and quantified fluorescence intensity were acquired to monitor the surgical margins. Results In cytological and animal experiments, the results showed it was feasible to monitor surgical margins with NIF imaging and spectroscopy. Fluorescence was detected in primary tumors in all patients. The fluorescence intensities of the tumor, peritumoral, and normal tissues were 398.863 ± 151.47, 278.52 ± 84.89, and 274.5 ± 100.93 arbitrary units (AUs), respectively (P < 0.05). The SBR of tumor to peritumoral tissue and normal tissues was computed to be 1.45 ± 0.36 and 1.56 ± 0.41, respectively. After primary tumor excision, the wounds showed abnormal fluorescence in four patients (4/20), and residual cancer cells were confirmed by pathological examination in two patients (2/20). Conclusion These findings confirmed the complementary value of NIF imaging during radical tumor resection of OSCC. Before tumor resection, we could utilize the fluorescence margin produced by ICG NIF imaging to determine the surgical margin. Moreover, after tumor blocks were removed, the status of surgical margin could also be evaluated rapidly by ICG NIF imaging of tumor bed and in vitro specimens.

This study reports a fluorescence ratio immunosensor method for detecting dibutyl phthalate (DBP) sensitively and specifically using dual-emission carbon quantum dots labelled with amino-modified nucleic acid aptamers. Under optimal experimental conditions, the linearity range of the method for detecting DBP was from 12.5 to 1500 μg/L, with a limit of detection of 5.0 μg/L. Compared with detection results for two structural analogues, this method showed good specificity for DBP. Liquor samples spiked with DBP measured by this method exhibited a standard recovery of 93.2% to 112.4% with a relative standard deviation of 1.59% to 4.54%. The method was used to determine the DBP content in edible oil samples, providing results not significantly different from those obtained by gas chromatography. Compared with the single wavelength emission method, this method had a stronger anti-interference ability and provided more accurate results, so can be used for highly sensitive detection of DBP in food samples.

Abstract Background Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer associated with a high mortality. Long non-coding RNAs (lncRNAs) have recently emerged as regulators in the development and progression of several cancers, and therefore represent an opportunity to uncover new targets for therapy. In the present study, we aimed to investigate the potential effect of lncRNA BZRAP1-AS1 on the angiogenesis of HCC. Methods Microarray-based data analysis was initially employed to screen genes and lncRNAs that are differentially expressed in HCC and the candidate BZRAP1-AS1 was identified as a hit. The expression of BZRAP1-AS1 and thrombospondin-1 (THBS1) in HCC tissues and cells were then determined using RT-qPCR. The gene methylation level was measured by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) assays. Next, the interactions between BZRAP1-AS1, DNA methyltransferase 3B (DNMT3b), and THBS1 were assessed by RIP, RNA pull-down and ChIP assays. Finally, the roles of BZRAP1-AS1, DNMT3b and THBS1 in angiogenesis in vitro as well as tumorigenesis in vivo were evaluated by a battery of the gain- and loss-of function experiments. Results BZRAP1-AS1 was identified as a highly expressed lncRNA in HCC tissues and cells. Down-regulation of BZRAP1-AS1 in HCC cells inhibited HUVEC proliferation, migration and angiogenesis. By interacting with DNMT3b, BZRAP1-AS1 induced methylation of the THBS1 promoter and inhibited the transcription of THBS1, resulting in promoted angiogenesis of HUVECs. Moreover, silencing of BZRAP1-AS1 repressed the angiogenesis as well as the tumor growth of HCC in vivo via up-regulating THBS1. Conclusion This study provides evidence that angiogenesis in HCC is hindered by silencing of BZRAP1-AS1. Thus, BZRAP1-AS1 may be a promising marker for the treatment of HCC.

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.

Psoriasis is a multifactorial immune-mediated disease. The highly effective and eligible treatment for psoriasis is limited, for its specific pathogenesis is incompletely elucidated. Skin microbiota is a research hotspot in the pathogenesis of immune-mediated inflammatory skin diseases nowadays, and it may have significant involvement in the provocation or exacerbation of psoriasis with broadly applicable prospects. It is postulated that skin microbiota alternation may interplay with innate immunity such as antimicrobial peptides and Toll-like receptors to stimulate T-cell populations, resulting in immune cascade responses and ultimately psoriasis. Achieving a thorough understanding of its underlying pathogenesis is crucial. Herein, we discuss the potential immunopathogenesis of psoriasis from the aspect of skin microbiota in an attempt to yield insights for novel therapeutic and preventive modalities for psoriasis.

In this paper, a novel biomimetic enzyme-linked immunoassay method (BELISA) was successfully established for the detection of histamine and tryptamine, based on catalytically active cupric oxide@gold nanoparticles (CuO@Au NPs) as a marker and a molecularly imprinted polymer (MIP) as the biomimetic antibody. Under optimized conditions, the detection limitations of the BELISA method for histamine and tryptamine were 0.04 mg L−1 and 0.14 mg L−1, respectively. For liquor spiked with histamine and tryptamine, the BELISA method delivered satisfactory recoveries ranging from 89.90% to 115.00%. Furthermore, the levels of histamine and tryptamine in fish, soy sauce, and rice vinegar samples were detected by the BELISA method and a high performance liquid chromatography method, with no significant difference between the two methods being found. Although the catalytic activity of nanozymes is still lower than that of natural enzymes, the BELISA method could still sensitively determine the histamine and tryptamine levels in food samples.

The mathematical model of optimal water quantity allocation for a single main canal in a large-scale irrigation area was constructed that took the minimal sum of the squared deviation of water shortage for water receiving areas controlled by the single main canal in one given irrigation period as the study target, and the total irrigation quantity of the single main canal as a constraint condition. Taking the optimal allocation of water quantity of each branch canal as decision variables, and several branch canals under the irrigation sequence of the main canal as a state variable, this model was solved by the one-dimensional dynamic programming (DP) method, by which the minimal water shortage and corresponding optimal water quantity allocation of each branch canal was calculated. The proposed method could provide a decision-making reference for optimal water resources allocation of single main canal irrigation areas, and also provide the theoretical basis for optimal water quantity allocation of a main canal with rotation irrigation by strips or with segmented rotation irrigation mode in China’s large-scale irrigation areas. Taking Hengliu Main Canal of Zhouqiao Irrigation Area in Jiangsu Province as a study case, optimization results showed that in a medium drought year (p = 75%) and a special drought year (p = 95%), minimal water shortage for water receiving areas controlled by Hengliu Main Canal was respectively 2.57 × 104 m3 and 23.31 × 104 m3 during the ponding period of rice. The corresponding water quantity allocation for each branch canal has reflected a compellent model solution precision and efficiency.