The usage and costs of national drug price-negotiated anticancer medicines in a first-tier city in Northeast China: a study based on health insurance data.

BACKGROUND: The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China. METHODS: We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region. RESULTS: During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients' payment capability level, but an increasing trend (11.94%-18.42) under rural patients' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend. CONCLUSION: This study demonstrates that access to drugs for urban cancer patients has improved. However, patients' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation's health insurance funds.

Programmable DNA Hydrogel Assisting Microcrystal Formulations for Sustained Locoregional Drug Delivery in Surgical Residual Tumor Lesions and Lymph Node Metastasis.

Surgical residual tumor lesions (R1 resection of surgical procedures (e.g., liver cancer infiltrating the diaphragm, surgical residual breast cancer, postoperative residual ovarian cancer) or boundary residual after ablation) and lymph node metastasis that cannot be surgically resected (retroperitoneal lymph nodes) significantly affect postoperative survival of tumor patients. This clinical conundrum poses three challenges for local drug delivery systems: stable and continuous delivery, good biocompatibility, and the ability to package new targeted drugs that can synergize with other treatments. Here, a drug-laden hydrogel generated from pure DNA strands and highly programmable in adjusting its mesh size is reported. Meanwhile, the DNA hydrogel can assist the microcrystallization of novel radiosensitizing drugs, ataxia telangiectasia and rad3-related protein (ATR) inhibitor (Elimusertib), further facilitating its long-term release. When applied to the tumor site, the hydrogel system demonstrates significant antitumor activity, minimized systemic toxicity, and has a modulatory effect on the tumor-immune cell interface. This drug-loaded DNA-hydrogel platform represents a novel modality for adjuvant therapy in patients with surgical residual tumor lesions and lymph node metastasis.

A meta-analysis of treatment for early-stage cervical cancer: open versus minimally invasive radical trachelectomy.

BACKGROUND: In previous systematic reviews, meta-analysis was lacking, resulting in the statistical difference between the data of different surgeries being impossible to judge. This meta-analysis aims to contrast the fertility results and cancer outcomes between open and minimally invasive surgery. METHOD: We systematically searched databases including PubMed, Embase, Cochrane, and Scopus to collect studies that included open and minimally invasive radical trachelectomy. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. RESULT: Eight studies (1369 patients) were incorporated into our study. For fertility results, the Open group excels MIS group in pregnancies-Third trimester delivery [OR = 2.68; 95% CI (1.29, 5.59); P = 0.008]. Nevertheless, there is no statistical difference in clinical pregnancy, miscarriage, and second-trimester rate. Concerning cancer outcomes, no difference was detected in the overall survival [OR = 1.56; 95% CI (0.70, 3.45); P = 0.27] and recurrence [OR = 0.63; 95% CI (0.35, 1.12); P = 0.12]. Concerning surgery-related outcomes, the comprehensive effects revealed that the estimated blood loss of the Open group was higher than that of the MIS group[MD = 139.40; 95% CI (79.05, 199.75); P < 0.0001]. However, there was no difference between the postoperative complication rate in the two groups [OR = 1.52; 95% CI (0.89, 2.60); P = 0.12]. CONCLUSION: This meta-analysis suggested that the fertility result of the Open group may be better than the MIS group, while the MIS group has better surgery-related outcomes. Owing to the poor cases of our study, a more robust conclusion requires more relevant articles in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022352999.

Association between serum copper level and reproductive health of Women in the United States: a cross-sectional study.

Copper is an indispensable trace element in metabolism. This study aimed to investigate the relationship between copper and reproductive health, and possibly provide new insights for diagnosis and treatment. This study was based on data extracted from the NHANES database (2013-2014 and 2015-2016). The t-test, ANOVA, Chi-square test, multiple linear regression, and restricted cubic spline analysis were used. Serum copper levels were significantly higher in women with gestational diabetes than in those without gestational diabetes (P = 0.0150). Women with higher copper levels and smoking habits tended to deliver overweight babies (P = 0.028). Women with diabetes had higher serum copper and were prone to deliver overweight babies (P = 0.024). Serum copper levels showed a positive relationship with sex hormone-binding globulin (SHBG) levels (P < 0.0001). In this study, serum copper levels were found to be associated with reproductive health in women. Further studies are required to draw causal inferences.

Case Report: A case of hepatocellular carcinoma with aberrant right hepatic artery treated with transarterial chemoembolization and infusion chemotherapy separately to bilobar lesion combining with systemic therapies and sequential hepatectomy.

Background: Hepatocellular carcinoma (HCC) with a dismal prognosis is the second most deadly malignancy globally. Surgery is believed to be a curative approach. Nevertheless, there is still a considerable probability of postoperative recurrence. Most patients present in advanced stages with a surgically and oncologically unresectable disease. Systemic medicines are increasingly important to downstage the disease and further improve survival. Case summary: A 67-year-old Chinese man with uncontrolled hepatitis B was discovered to have liver masses with abnormal serum vitamin K absence or antagonist-II (PIVKA-II) level during checkup for upper abdominal discomfort. Abdominal multiphase computerized tomography (CT) and gadoxetate disodium-enhanced magnetic resonance imaging (MRI) showed the bulky bilobar HCCs of Barcelona Clinic Liver Cancer stage B and China Liver Cancer Staging stage IIa. Furthermore, the aberrant right hepatic artery (RHA) originates from the superior mesenteric artery. Due to the location being adjacent to important vasculatures and massive size of the right-sided lesion, curative resection appears to be challenging. To achieve a favorable surgical margin, repeated hepatic arterial infusion chemotherapy (HAIC) was adopted through the variant RHA, while transarterial chemoembolization (TACE) was delivered to the left lobe to arrest tumor growth. Furthermore, sintilimab plus lenvatinib served as the sequential systemic therapy. After 5 months of conversion treatment, the partial response with a decreased serum PIVKA-II level was attained. The R0 hepatectomy was then performed without postoperative complications. The immunohistochemistry and next-generation sequencing results suggested that the two-side HCCs existing tumor heterogeneity were not completely consistent. The patient continues to be without evidence of disease. Conclusion: Our case highlights a favorable outcome in a man with bilobar bulky HCC after undergoing the comprehensive therapeutic schedule that includes personalized intervention and systemic drug therapy. In terms of conversion therapy, our case provides a secure and practical reference for managing unresectable bilobar HCC coexisting with the aberrant hepatic artery.

Trophoblastic mitochondrial DNA induces endothelial dysfunction and NLRP3 inflammasome activation: Implications for preeclampsia.

AIMS: Preeclampsia (PE) is characterised by systemic vascular endothelium dysfunction. Circulating trophoblastic secretions contribute to endothelial dysfunction, resulting in PE; however, the underlying mechanisms remain unclear. Herein, we aimed to determine the potential correlation between the release of trophoblastic mitochondrial deoxyribonucleic acid (DNA) (mtDNA) and endothelium damage in PE. MATERIALS AND METHODS: Umbilical cord sera and tissues from patients with PE were investigated for inflammasome activation. Following this, trophoblastic mitochondria were isolated from HTR-8/SVneo trophoblasts under 21 % oxygen (O2) or hypoxic conditions (1 % O2 for 48 h) for subsequent treatments. Primary human umbilical veinendothelial cells (HUVECs) were isolated from the human umbilical cord and then exposed to a vehicle (phosphate-buffered saline [PBS]), mtDNA, hypo-mtDNA, or hypo-mtDNA with INF39 (nucleotide oligomerisation domain-like receptor family pyrin domain containing 3 [NLRP3]-specific inhibitor) for 12 h before flow cytometry and immunoblotting. The effects of trophoblastic mtDNA on the endothelium were further analysed in vivo using enzyme-linked immunosorbent assay (ELISA) and vascular reactivity assay. The effects of mtDNA on vascular phenotypes were also tested on NLRP3 knockout mice. RESULTS: Elevated interleukin (IL)-1ß in PE sera was accompanied by NLRP3 inflammasome activation in cord tissues. In vitro and in vivo experiments revealed that the release of trophoblastic mtDNA could damage the endothelium via NLRP3 activation, resulting in the overexpression of NLRP3, caspase-1 p20, IL-1ß p17, and gasdermin D (GSDMD); reduced endothelial nitric oxide synthase (eNOS) levels; and impaired vascular relaxation. Flow cytometric analysis confirmed that extensive cell death was induced by mtDNA, and simultaneously, a more pronounced pro-apoptotic effect was caused by hypoxia-treated trophoblastic mtDNA. The NLRP3 knockout or pharmacologic NLRP3 inhibition partially reversed tumour necrosis factor-α (TNF-α) and IL-1ß levels and endothelium-dependent vasodilation in mice. CONCLUSION: These findings demonstrate that trophoblastic mtDNA induced NLRP3/caspase-1/IL-1ß signalling activation, eNOS-related endothelial injury, and vasodilation dysfunction in PE.

PCSK9 Promotes Endothelial Dysfunction During Sepsis Via the TLR4/MyD88/NF-κB and NLRP3 Pathways.

Endothelial dysfunction often accompanies sepsis. We aimed to explore the role of PCSK9 in septic endothelial dysfunction. Sepsis was induced by lipopolysaccharide (LPS) treatment of human umbilical vein endothelial cells (HUVECs) in vitro and cecal ligation and puncture (CLP) surgery in mice in vivo. Evolocumab (EVC) and Pep 2-8, PCSK9 inhibitors, were subsequently used to determine the role of PCSK9 in sepsis-induced endothelial dysfunction in vitro and in vivo, respectively. In addition, the TLR4 agonist, Kdo2-Lipid A ammonium (KLA), was used to determine the related mechanism. Protein expression of eNOS, VE-cadherin, PCSK9, TLR4, MyD88, p-p65, p65, NLRP3, ASC, and caspase-1 p20 in mice aortas and HUVECs was measured by western blotting, while mRNA expression of TNFα, IL-1ß, and IL-18 was determined by qRT-PCR. The level of inflammatory cytokines of mouse aortas was visualized by immunohistochemistry. Vasodilation of the aorta was detected by vascular reactivity experiments. The 96-h survival rate after CLP was assessed. Our findings showed that the expression of eNOS and VE-cadherin decreased, and PCSK9 expression increased, in septic HUVECs or mice. Inhibition of PCSK9 increased eNOS and VE-cadherin expression. Activation of the TLR4/MyD88/NF-κB and NLRP3 pathways may be responsible for PCSK9-induced endothelial dysfunction in sepsis. Vascular reactivity tests and survival studies showed that inhibition of PCSK9 could prevent the decrease in endothelium-dependent vasodilation function and improve the survival rates of septic mice. In summary, our results suggested that increased PCSK9 expression during sepsis activated the TLR4/MyD88/NF-κB and NLRP3 pathways to induce inflammation, which resulted in vascular endothelial dysfunction and decreased survival rates. Thus, inhibition of PCSK9 may be a potential clinical therapeutic target to improve vascular endothelial function in sepsis.

Two-Dimensional Shear Wave Elastography Evaluation of Post-transplantation Complications in Pediatric Receipt: A Retrospective Cohort.

Background: The 20-year survival rate in pediatric patients after liver transplantation (LT) was no more than 70%. Hepatic fibrosis is one of the principal factors affecting the long-term prognosis. Imaging evaluation was the first-line examination for pediatric liver graft assessment. However, the sensitivity and specificity were insufficient. Thus, two-dimensional shear wave elastography (2D-SWE) was performed to evaluate liver graft stiffness and complication in post-transplant pediatric receipt. Materials and Methods: In this retrospective cohort, 343 pediatric recipients who underwent liver graft biopsy in our tertiary LT center were recruited between June 2018 and December 2020. The 2D-SWE evaluation, laboratory examination, routine post-transplant biopsy, and hepatic pathological assessment were performed. Results: Ninety-eight of the 343 pediatric patients were included according to the protocol. The Liver Stiffness Measurements (LSM) value of 2D-SWE was significantly elevated in post-transplant fibrosis (p < 0.0001). The LSM value of patients with post-transplant biliary complications (p < 0.0001) and biopsy-proven rejection (BPR, p = 0.0016) also rose compared to regular recovery patients. Concerning the sensitivity and specificity of 2D-SWE in diagnosing liver graft fibrosis, the area under the ROC curve (AUC) was 88%, and the optimal cutoff value was 10.3 kPa. Conclusion: Pediatric LSM by 2D-SWE was efficient. Routine 2D-SWE evaluation could be optimal to predict significant liver graft fibrosis.

Aggregation-Induced Emission (AIE) and Magnetic Resonance Imaging Characteristics for Targeted and Image-Guided siRNA Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains a global health challenge. Small interfering RNA (siRNA) is a promising therapeutic modality that blocks multiple disease-causing genes without impairing cell structures. However, siRNA therapeutics still have off-target proportion and lack effective quantitative analysis method in vivo. Thus, a novel theragnostic nanoparticle with dual-mode imaging is synthesized for targeted and image-guided siRNA therapy of HCC. Survivin siRNA is carried by Poly-ethylenimine (PEI) and interacted with T7-AIE/Gd NPs, which are self-assembled of DSPE-PEG-DTPA(Gd), DSPE-PEG-Mal, DSPE-PEG-PEI, and TPE. The resulting theragnostic nanoparticles exhibit lower toxicity and high therapeutic effect, and excellent T1-weighted magnetic resonance imaging (MRI) and aggregation-induced emission (AIE) imaging performance. Moreover, in vivo MRI and AIE imaging indicate that this kind of theragnostic nanoparticles rapidly accumulates in the tumor due to active targeting and enhanced permeability and retention (EPR) effects. Sur@T7-AIE-Gd suppresses HCC tumor growth by inducing autophagy and destabilizes DNA integrity in tumor cells. The results suggest that T7-AIE-Gd nanoparticles carrying Survivin siRNA with dual-mode imaging characteristics are promising for targeted and image-guided siRNA therapy of hepatocellular carcinoma.

ß2-Adrenergic Receptor Enhances the Alternatively Activated Macrophages and Promotes Biliary Injuries Caused by Helminth Infection.

The autonomic nervous system has been studied for its involvement in the control of macrophages; however, the mechanisms underlying the interaction between the adrenergic receptors and alternatively activated macrophages (M2) remain obscure. Using FVB wild-type and beta 2 adrenergic receptors knockout, we found that ß2-AR deficiency alleviates hepatobiliary damage in mice infected with C. sinensis. Moreover, ß2-AR-deficient mice decrease the activation and infiltration of M2 macrophages and decrease the production of type 2 cytokines, which are associated with a significant decrease in liver fibrosis in infected mice. Our in vitro results on bone marrow-derived macrophages revealed that macrophages from Adrb2-/- mice significantly decrease M2 markers and the phosphorylation of ERK/mTORC1 induced by IL-4 compared to that observed in M2 macrophages from Adrb2+/+ . This study provides a better understanding of the mechanisms by which the ß2-AR enhances type 2 immune response through the ERK/mTORC1 signaling pathway in macrophages and their role in liver fibrosis.

Congenital disorder of glycosylation caused by mutation of ATP6AP1 gene (c.1036G>A) in a Chinese infant: A case report.

BACKGROUND: The ATP6AP1 gene coding for the accessory protein Ac45 of the vacuolar-type adenosine triphosphatases (V-ATPase) is located on chromosome Xq28. Defects in certain subunits or accessory subunits of the V-ATPase can lead to congenital disorders of glycosylation (CDG). CDG is a group of metabolic disorders in which defective protein and lipid glycosylation processes affect multiple tissues and organs. Therefore, the clinical presentation of patients with ATP6AP1-CDG varies widely. In this report, we present a case of ATP6AP1-CDG in a Chinese infant, with clinical features and genotype. CASE SUMMARY: An 8-mo-old boy was admitted to our hospital because unexplained hepatosplenomegaly and elevated transaminases that had been noted while he was being treated for a cough at a local hospital. A post-admission examination at our hospital revealed abnormalities in the infant's liver, brain, and immune system. Trio-based whole exome gene analysis identified a hemizygous pathogenic mutation c.1036G>A (p.E346K) in exon 9 of the ATP6AP1 gene. This variant of the ATP6AP1 gene has not been reported in East Asian countries until now. CONCLUSION: Based on the infant's clinical manifestations and the results of genetic detection, he was clearly diagnosed with ATP6AP1-CDG. The clinical manifestations of children with CDG vary widely. Genetic testing analysis helps in the clinical diagnosis of children with CDG.

Neoadjuvant Programmed Cell Death 1 (PD-1) Inhibitor Treatment in Patients With Hepatocellular Carcinoma Before Liver Transplant: A Cohort Study and Literature Review.

Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.

A simple noninvasive model to predict significant fibrosis in children with chronic hepatitis B.

ABSTRACT: To develop a noninvasive model to predict significant fibrosis in children with chronic hepatitis B (CHB).A total of 116 CHB pediatric patients who underwent liver biopsy were included in the study. Liver histology, which is the gold standard for assessing fibrosis, was performed. Blood routine examination, coagulation function, liver biochemistry, viral serology, and viral load were analyzed. Receiver operating characteristic curve analysis was used to analyze the sensitivity and specificity of all possible cut-off values.Based on the correlation and difference analyses, 7 available clinical parameters (total bile acid, gamma-glutamyl transpeptidase [GGT], aspartate transaminase, direct bilirubin to total bilirubin ratio, alanine aminotransferase, prealbumin [PA], and cholinesterase) were included in the modeling analysis. A model to predict significant liver fibrosis was derived using the 2 best parameters (PA and GGT). The original model was . After the mathematical calculation, the G index=600 × GGT/PA2 predicted significant fibrosis, with an area under the receiving operating characteristics (AUROC) curve of 0.733, 95% confidence interval (0.643-0.811). The AUROC of the G index (0.733) was higher than that of aminotransferase to platelet ratio index (APRI) (0.680) and Fibrosis index based on 4 factors (FIB-4) (0.601) in predicting significant fibrosis in children with CHB. If the values of the G index were outside the range of 0.28 to 1.16, 52% of children with CHB could avoid liver biopsy, with an overall accuracy of 75%.The G index can predict and exclude significant fibrosis in children with CHB, and it may reduce the need for liver biopsy in children with CHB.

Chronic overload of concentration-dependent iron exerts different effects on ovarian function in C57BL/6J mice†.

Overloaded iron can deposit in the reproductive system and impair ovarian function. But few studies have identified the exact effect of overloaded iron on the endocrine function and fertility capacity in female mice. Here, we established iron-overloaded mouse models by intraperitoneal injection of iron dextran to adult female C57BL/6J mice at 0.1 g/kg (LF group), 0.5 g/kg (MF group), and 1.0 g/kg (HF group) concentrations once a week for eight consecutive weeks. We found that overloaded iron resulted in smaller ovaries, as well as accumulated oxidative damages. The endocrine function and follicle development were also impeded in the MF and HF groups. The 10-month breeding trial indicated that (1) Low concentration of iron (0.1 g/kg) wasn't detrimental to the ovary; (2) Middle concentration of iron (0.5 g/kg) impeded the childbearing process, though it could be recovered following the iron excretion; and (3) High concentration of iron (1.0 g/kg) damaged the fertility, even gave rise to sterility. Yet for those fertile mice, litter number and litter size were smaller and the ovarian reserve of their offspring was impaired. Transcriptome profiling results indicated that overloaded iron could compromise ovarian function by disrupting ovarian steroidogenesis, interfering with ovarian microenvironment, and inhibiting Wnt signaling. Taken together, we have demonstrated the effect that chronic concentration-dependent iron overload exerted on mouse ovarian function, which may act as a preliminary basis for further mechanism and intervention investigations.

Palmitoylation in Crohn's disease: Current status and future directions.

S-palmitoylation is one of the most common post-translational modifications in nature; however, its importance has been overlooked for decades. Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract. Bowel damage and subsequent disabilities caused by CD are a growing global health issue. Well-acknowledged risk factors for CD include genetic susceptibility, environmental factors, such as a westernized lifestyle, and altered gut microbiota. However, the pathophysiological mechanisms of this disorder are not yet comprehensively understood. With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD, as recently reported, there is a need to investigate the relationship between CD and S-palmitoylation. In this review, we summarize the concept, detection, and function of S-palmitoylation as well as its potential effects on CD, and provide novel insights into the pathogenesis and treatment of CD.

Design of bovine lactoferricin-derived peptide and its expression and activity in Pichia pastoris.

Bovine lactoferrin peptide has been shown to be a broad-spectrum antimicrobial peptide. Based on the relationship between the structure and function of antimicrobial peptides, the antimicrobial peptide databases and protein analysis software were used to optimize the design of bovine lactoferricin peptide (LfcinB). The designed bovine lactoferricin-derived peptide (LfcinBD) gene fragment was inserted into a pPIC9K-His plasmid to construct a recombinant expression vector. After linearization of the Recombinant plasmid, Pichia pastoris GS115 cells were transfected with linearized recombinant plasmid by using electroporation and LfcinBD gene expression was induced with methanol. After the fermentation, supernatant was separated by low-temperature high-speed centrifugation. Ultrafiltration and freeze drying of the fermentation supernatant were performed, purified. Experimental results showed that the LfcinBD had stronger bacteriostatic activity against Staphylococcus aureus than the natural bovine lactoferrin peptide (LfcinB) produced under the same fermentation conditions. The effective expression of the optimized bovine lactoferricin-derived peptide was detected using SDS-PAGE electrophoresis. This study lays the foundation for further exploration to improve the biological activities of antimicrobial peptides.

Adventitial Cell Atlas of wt (Wild Type) and ApoE (Apolipoprotein E)-Deficient Mice Defined by Single-Cell RNA Sequencing.

Objective- Vascular adventitia encompasses progenitors and is getting recognized as the major site of inflammation in early stage of atherosclerosis. However, the cellular atlas of the heterogeneous adventitial cells, the intercellular communication, the cellular response of adventitia to hyperlipidemia, and its contribution to atherosclerosis have been elusive. Approach and Results- Single-cell RNA sequencing was applied to wt (wild type) and ApoE (apolipoprotein E)-deficient aortic adventitia from 12-week-old C57BL/6J mice fed on normal laboratory diet with early stage of atherosclerosis. Unbiased clustering analysis revealed that the landscape of adventitial cells encompassed adventitial mesenchyme cells, immune cells (macrophages, T cells, and B cells), and some types of rare cells, for example, neuron, lymphatic endothelial cells, and innate lymphoid cells. Seurat clustering analysis singled out 6 nonimmune clusters with distinct transcriptomic profiles, in which there predominantly were stem/progenitor cell-like and proinflammatory population (Mesen II). In ApoE-deficient adventitia, resident macrophages were activated and related to increased myeloid cell infiltration in the adventitia. Cell communication analysis further elucidated enhanced interaction between a mesenchyme cluster and inflammatory macrophages in ApoE-deficient adventitia. In vitro transwell assay confirmed the proinflammatory role of SCA1+ (stem cell antigen 1 positive) Mesen II population with increased CCL2 (chemokine [C-C motif] ligand 2) secretion and thus increased capacity to attract immune cells in ApoE-deficient adventitia. Conclusions- Cell atlas defined by single-cell RNA sequencing depicted the heterogeneous cellular landscape of the adventitia and uncovered several types of cell populations. Furthermore, resident cell interaction with immune cells appears crucial at the early stage of atherosclerosis.

Primary thyroid Burkitt lymphoma in a 15-year-old boy.

In children, primary thyroid Burkitt lymphoma (PTBL) is an extremely rare pathologic entity of thyroid malignant tumor. Here we describe a case of PTBL in a 15-year-old boy, who developed a rapidly enlarging neck mass that showed signs of compression. The color Doppler ultrasound revealed diffuse swelling of the thyroid gland, with a solid and irregular mass from the left to the isthmus, which was about 8 × 7 × 5 cm in size. Computed tomography showed Irregular masses were seen in the left thyroid with a range of about 7.1 × 5.4 × 8.0 cm, and a beaded slightly enlarged lymph node with a maximum of 1.6 × 0.8 cm was discovered in the left neck. Postoperative pathologic examination also found the specific starry-sky phenomenon of Burkitt lymphoma. Moreover, immunohistochemistry also indicated that the related cellular immunophenotypic expression was also positive or negative. In particular, the proliferation rate by ki67 was almost 100% and C-MYC was also positive. After thyroidectomy, patient underwent four cycles of CHOP regimen chemotherapy. Unfortunately, the patient died as a result of the deterioration of his condition. This report provides an opportunity to review an uncommon type of PTBL in children.

Hepatic fibrosarcoma in a middle-aged man.

Hepatic fibrosarcoma (HF) is a rare sarcoma with a high malignancy and a poor prognosis. Moreover, it is hard to diagnose before completing a pathological examination, for HF has almost no features of clinical or imaging manifestations. Here we report a case of HF in a 42-year-old male who complained of pain in the right upper abdomen. Computed tomography (CT) and ultrasonography confirmed a large mass was occupying the right lobe of his liver. The patient was finally diagnosed with HF based on the morphology and immunohistochemistry of the tumor after resection. This case indicates that a diagnosis of HF should be considered, especially when the results of imaging examinations and tumor markers do not support the common hepatic diseases.

Comprehensive analysis of long non-coding RNA PVT1 gene interaction regulatory network in hepatocellular carcinoma using gene microarray and bioinformatics.

PVT1 has been reported to be involved in the tumorigenesis and development of different cancers. However, the role of PVT1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we applied gene microarray analysis to detect differentially expressed genes (DEGs) between PVT1 RNAi groups and controls. We initially investigated and confirmed PVT1 expression in HCC using The Cancer Genome Atlas (TCGA). The potential genes and pathways associated with PVT1 were also analyzed. We also performed bioinformatics analyses (Gene Ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) to explore the underlying pathways and networks of these potential genes. We selected DLC1 for further analysis. Based on the TCGA database, PVT1 was markedly up-regulated in HCC, whereas DLC1 was down-regulated. Moreover, PVT1 expression negatively correlated with DLC1 in HCC, an observation that has been further validated in different cohorts with Oncomine. High expression of PVT1 was positively associated with gender, race, vascular invasion and pathological grade in HCC. Additionally, the ROC curve indicated that both PVT1 and DLC1 have high diagnostic value in HCC. We speculated that PVT1 might play a significant role in HCC development and progression via regulation of various pathways and genes, especially DLC1 and the Hippo signaling pathway. However, this mechanism should be confirmed by functional experiments.