Cationic amphiphilic molecules as novel sclerosants for venous malformation treatment: A study on tranexamic acid-derived low-molecular-weight gels.

Venous malformation (VM) is a prevalent congenital vascular anomaly characterized by abnormal blood vessel growth, leading to disfigurement and dysfunction. Sclerotherapy, a minimally invasive approach, has become a primary therapeutic modality for VM, but its efficacy is hampered by the rapid dilution and potential adverse effects. In this study, we introduced a series of cationic amphiphilic molecules, fatty alcohol esters (TA6, TA8, and TA9) of tranexamic acid (TA), which self-assembled into low-molecular-weight gels (LMWGs) in water. The TA9, in particular, is released slowly when hydrogel is injected into the vein locally. Then, it damages the venous wall by destroying cell membranes and precipitating proteins, causing inflammation and thrombosis, thickening of the venous wall, effectively inducing irreversible vein fibrosis. Additionally, TA9 can be rapidly degraded into TA in plasma to reduce toxicity caused by diffusion. Overall, this study suggests that the cationic amphiphilic molecule TA9 is a promising sclerosant for VM treatment, offering a novel, effective, and safe therapeutic option with potential for clinical translation.

PTPN2 inhibits the proliferation of psoriatic keratinocytes by dephosphorylation of STAT3.

Psoriasis is a recurrent and protracted disease that severely impacts the patient's physical and mental health. Thus, there is an urgent need to explore its pathogenesis to identify therapeutic targets. The expression level of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) was analyzed by immunohistochemistry techniques in psoriatic tissues and imiquimod-induced psoriatic mouse models. PTPN2 and signal transducer and activator of transcription 3 (STAT3) were overexpressed or silenced in human keratinocytes or an interleukin (IL)-6-induced psoriasis HaCaT cell model using overexpression plasmid transfection or small interfering RNA technology in vitro, and the effects of PTPN2 on STAT3, HaCaT cell function, and autophagy levels were investigated using reverse transcription-quantitative polymerase chain reaction, Western blot, Cell Counting Kit 8, 5-ethynyl-20-deoxyuridine, flow cytometry, and transmission electron microscopy. PTPN2 expression was found to be significantly downregulated in psoriatic tissues. Then, the in vitro antipsoriatic properties of PTPN2 were investigated in an IL-6-induced psoriasis-like cell model, and the results demonstrated that inhibition of keratinocyte proliferation by PTPN2 may be associated with elevated STAT3 dephosphorylation and autophagy levels. These findings provide novel insights into the mechanisms of autophagy in psoriatic keratinocytes and may be essential for developing new therapeutic strategies to improve inflammatory homeostasis in psoriatic patients.

Application of 'CDC- Public Security Bureau-NGO' Joint Prevention and Control Mechanism Allied AIDS prevention and control in Guigang, Guangxi.

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: The research design of this study incorporates both a serial cross-sectional study and time-series analysis from 2014 to 2021, 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. 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. Mann-Kendall test and descriptive methods were used to analyzed the trend of traditional and innovative interventions models on HIV positive detection rate in FSWs and elderly clients. RESULTS: The condom usage rates during the last commercial sexual encounter for FSWs and elderly clients improved from 74.9% and 9.1%, respectively, to 96.9% and 28.1%. (P < 0.05), newly reported cases of HIV have decreased by 15.56% yearly and the HIV positive detection rate among middle-aged and elderly people has dropped by 14.47%. 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.

Treatment of Netherton Syndrome in Pediatrics with Upadacitinib.

Background: Netherton syndrome, a rare autosomal recessive genetic disease, lacks effective treatment options. This article presents a novel case of successful Upadacitinib therapy in a 14-year-old boy with Netherton syndrome. Case Presentation: A 14-year-old male with a lifelong history of dry skin, erythema, scaling, itching, and notable body odor was evaluated. These symptoms, accompanied by irregular hair growth and delayed development, prompted an initial diagnosis of atopic dermatitis at a local hospital. Treatment with antihistamines, moisturizers, and topical corticosteroids failed to alleviate systemic manifestations of red patches and persistent itching. Seeking further evaluation, the patient was presented to our center. Upon examination, the characteristics of "bamboo hair" and "golf tee sign" were observed microscopically in the patient's hair. Whole exome sequencing identified a paternally inherited mutation in the SPINK5 gene, confirming Netherton syndrome. No mutations were found in the mother. Despite initial positive responses to Secukinumab and Dupilumab, therapeutic efficacy waned over time. Results and Conclusions: Initiation of Upadacitinib at a daily dose of 15 mg yielded significant therapeutic benefits within a short timeframe. This study marks the first documented use of Upadacitinib in pediatric Netherton syndrome treatment. This case highlights the efficacy of Upadacitinib in treating Netherton syndrome, particularly in pediatric patients. Further studies are warranted to elucidate its long-term effects and optimal dosing regimens.

Tofu wastewater as a carbon source flowing into municipal wastewater treatment plants for reductions of costs and greenhouse gas emissions.

Wastewater treatment processes significantly contribute to greenhouse gas (GHG) emissions. Municipal wastewater treatment also faces challenges related to low strength and a low carbon-to-nitrogen (C/N) ratio. This study investigates the high-carbon tofu wastewater flowing into municipal sewers for co-treatment at a wastewater treatment plant (WWTP) directly, with the goal of enhancing nitrogen removal and reduce GHG emissions. Within the framework of a circular economy for wastewater treatment, tofu wastewater serves as an external carbon source for sustainable solutions. The concentrated tofu wastewater had an average chemical oxygen demand (CODCr) of 21,894 ± 11,485 mg/L, total nitrogen (TN) of 591.8 ± 238.2 mg/L, and a C/N ratio of 36.9 ± 7.4. The denitrification rate reached 3.05 mg NO3--N/(g MLVSS·h). Therefore, tofu wastewater is a suitable alternative carbon source. A full-scale WWTP with a capacity of 20,000 m³/day was monitored from 2017 to 2022 to evaluate the co-treatment effects of municipal wastewater and tofu wastewater. The results showed an increase in 53.3% in the average CODCr concentration of the influent wastewater, while the total nitrogen and total phosphorus removal efficiencies were enhanced to 75.8% and 95.2%, respectively. In addition, the study quantified GHG emissions from tofu wastewater and municipal wastewater treatment. Compared to separate treatment processes, the co-treatment reduced GHG emissions by 337.9 t CO2-eq., approximately 15.8% of the total emissions of WWTP, and achieved a cost saving of 7-10% of the total operational costs. These findings demonstrate the environmental and economic advantages of integrating high-carbon industrial wastewater treatment directly into wastewater treatment plants.

Study of vascular sclerosing agent based on the dual mechanism of vascular endothelial cell damage-plasmin system inhibition.

Venous malformations are a vascular disorder. Currently, the use of chemical sclerosing agents is a common clinical approach for the treatment of venous malformations. However, the effectiveness of existing sclerosing agents is unsatisfactory and often accompanied by severe side effects. In this study, we have developed a novel cationic surfactant-based sclerosing agent (POL-TA) by conjugating the plasmin inhibitor tranexamic acid (TA) with a nonionic surfactant polidocanol (POL) through an ester bond. POL-TA induces endothelial cell damage, triggering the coagulation cascade and thrombus formation. Moreover, it releases TA in vivo, which inhibits plasmin activity and the activation of matrix metalloproteinase (MMPs), thereby stabilizing the fibrin network of the thrombus and promoting vascular fibrosis. We have established a cell model using venous malformation endothelial cells and assessed the cellular damage and underlying mechanisms of POL-TA. The inhibitory effects of POL-TA on the plasmin-MMPs system were evaluated using MMP-9 activity assay kit. Additionally, the mice tail vein model was employed to investigate the vascular sclerosing effects and mechanisms of POL-TA.

Associations of financial toxicity with symptoms and unplanned healthcare utilization among cancer patients taking oral chemotherapy at home: a prospective observational study.

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.

Lamina Abrasion Caused by High-Speed Drill in Unilateral Door Cervical Laminoplasty: A Clinical Investigation.

BACKGROUND The association of laminar opening extent (LOE) with sagittal canal diameter (SCD) and the cross-sectional area (CSA) in unilateral door cervical laminoplasty (UDCL) was previously analyzed. However, the lamina abrasion has been neglected, which could lead to unreliable results. The present study aims to develop the concept of effective laminar opening extent (ELOE) with consideration of the lamina abrasion and to analyze the relationships between ELOE and SCD as well as the CSA of the spinal canal. MATERIAL AND METHODS A total of 138 patients treated by UDCL were included. Pre- and postoperative SCDs and CSAs and cervical Japanese Orthopaedic Association (JOA) scores were compared to verify the effectiveness of the surgery. Linear and curvilinear regression models were used to assess the association between postoperative SCD/CSA increases and ELOE. RESULTS All surgeries were successfully performed. A total of 602 mini-plates were used, and 12-mm mini-plates was the most often used (n=402, 66.78%), while 16-mm were used the least (n=25, 4.15%). The SCDs, CSAs, and JOA scores were increased significantly after surgery (P0.939, P0.938, P.

Associations of readiness for hospital discharge with symptoms and non-routine utilization of post-discharge services among cancer patients receiving oral chemotherapy at home: A prospective study.

BACKGROUND: Readiness for hospital discharge is associated with patients' health outcomes after they return home. However, little is known about this association among cancer patients receiving oral chemotherapy at home. This study aimed to examine whether patients' reported readiness for hospital discharge was associated with symptoms and non-routine utilization of post-discharge services among cancer patients receiving oral chemotherapy at home. METHODS: A prospective study was conducted, and 151 cancer patients receiving oral chemotherapy were recruited from a provincial level hospital in South China between October 2018 and December 2019. The primary outcome was readiness for hospital discharge assessed by the Readiness for Hospital Discharge Scale-Short Form on the day of discharge. The secondary endpoints were symptoms assessed by MD Anderson Symptom Inventory and non-routine utilization of post-discharge services within one cycle of chemotherapy at home (21 days). RESULTS: Among these 151 participants, 74.2% of them reported as ready for discharge. Patients who were employed, lived in suburban area or villages, had a higher Eastern Cooperative Oncology Group score, took Tegafur as oral chemotherapy, and took oral chemotherapy for the first time reported lower readiness for hospital discharge. These five factors explained 28.1% of variance in readiness for hospital discharge. Patients who were not ready for discharge were prone to report higher symptom severity (p = 0.038). No differences in non-routine utilization of post-discharge services were found between the readiness versus non-readiness for discharge groups (p = 0.891). CONCLUSIONS: Most cancer patients receiving oral chemotherapy at home were ready for discharge, which was influenced by employment status, residence status, Eastern Cooperative Oncology Group score, type of oral chemotherapy drug, and the experience of taking oral chemotherapy at home. Patients with lower readiness reported worse symptom severity at home. Routine assessment was suggested to recognize unready patients, and more extensive preparations for discharge were recommended to help them manage symptoms at home.

Investigating the genomic alteration improved the clinical outcome of aged patients with lung carcinoma.

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.

Erythrocyte Membrane-Coated Invisible Acoustic-Sensitive Nanoparticle for Inducing Tumor Thrombotic Infarction by Precisely Damaging Tumor Vascular Endothelium.

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.

Predictors of oral chemotherapy adherence at home among Chinese cancer patients: An observational prospective study.

AIMS AND OBJECTIVES: 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. BACKGROUND: 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. DESIGN: An observational prospective study. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. RELEVANCE TO CLINICAL PRACTICE: Preventive interventions should focus on patients with previous medication non-adherence experience at discharge and experiencing numbness to promote oral chemotherapy adherence.

A Capillary Electrophoresis Method Based on Molecularly Imprinted Solid-Phase Extraction for Selective and Sensitive Detection of Histamine in Foods.

In this study, a sensitive capillary electrophoresis (CE) method based on molecularly imprinted solid-phase extraction (MISPE) was proposed to determine histamine in foods. A molecularly imprinted polymer (MIP) synthesized by bulk polymerization was used as the MISPE adsorbent for the selective extraction of histamine. Under the optimal conditions, the MISPE-CE method possessed good linearity for histamine detection in the concentration range of 0.1-100.0 µg/L. The limit of detection and limit of quantification of the method were calculated to be 0.087 µg/L and 0.29 µg/L, respectively. The histamine in spiked rice vinegar and liquor samples were detected by the developed method with recoveries of 92.63-111.00%. The histamine contents in fish, prawn, pork, chicken breast and soy sauce samples were determined using the developed method and a high-performance liquid chromatography method, with no significant difference found between the two methods.

Rhodiola rosea polysaccharides promote the proliferation of bone marrow haematopoietic progenitor cells and stromal cells in mice with aplastic anaemia.

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 < 0.01). High-dose RRPs significantly increased the formation of colony-forming unit-granulocyte macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E; p < 0.01). Fas and FasL protein expression in BMSCs decreased after RRPs administration. Especially at the high dose, RRPs (150 µg/mL) significantly promoted in vitro CFUs-E, BFUs-E, and CFUs-GM formation. RRPs (150-300 µg/mL) also promoted BMSC proliferation. DISCUSSION AND CONCLUSIONS: RRPs helped to promote haematopoietic recovery in mice with aplastic anaemia, facilitating haematopoietic tissue recovery. This study indicated some mechanisms of the haematopoietic regulatory effects of RRPs. Our findings provide a laboratory basis for clinical research on RRPs.

Tocilizumab, an Exploratory Treatment for Severe COVID-19 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.

Transcriptome wide analysis of long non-coding RNA-associated ceRNA regulatory circuits in psoriasis.

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.

Evaluation of short-term (16-week) effectiveness and safety of guselkumab in patients with psoriasis: A prospective real-life study on the Chinese population.

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.

Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12-dimethylbenz[a]anthracene-induced hamster oral cancer via the down-regulation of PI3K/AKT/mTOR signaling pathways.

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.

Identification of potential key mRNAs and LncRNAs for psoriasis by bioinformatic analysis using weighted gene co-expression network analysis.

Psoriasis is a common chronic autoimmune inflammatory skin disease that involves genetic and environmental factors. To date, psoriasis is still incurable. Thus, detection of its underlying molecular mechanisms is urgent. Weighted gene co-expression network analysis (WGCNA) was performed on the basis of the RNA-Seq data of psoriatic and normal (NN) skin tissues to detect the key mRNAs and long non-coding RNAs (LncRNAs) implicated in psoriasis and to identify psoriasis-related gene modules. Subsequently, 23 independent modules were obtained, and the pink module that contained differentially expressed 212 mRNAs and 100 LncRNAs was the most remarkable. Differentially expressed genes (DEGs) between psoriasis and healthy control in other RNA-Seq and microarray datasets were integrated to identify convinced psoriasis-associated genes. A total of 312 genes in the pink module and 613 DEGs were scanned. Eleven overlapped key mRNAs were identified, including two known genes (e.g., KRT15 and CCL27) and nine novel ones (e.g., ARSF, CLDN1, DACH1, LONRF1, PAMR1, RORC, SLC26A2, STS, UNC93A). A total of 11 key mRNAs were selected to construct a co-expression network to investigate potential candidate LncRNAs. Seventy-six pairs of LncRNA-mRNA co-expression relationships were found. To validate the findings, CCL27 and LncRNA-AL162231.4 expressions were detected in psoriatic and NN skin tissues. Result of RT-qPCR showed that CCL27 and LncRNA-AL162231.4 decreased in psoriatic lesions with statistical significance (P ≤ 0.05). Our study provides a new direction for elucidating the pathogenesis of psoriasis, but further experiments are still required.

KIT-related piebaldism in a Chinese girl.

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.