Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

BACKGROUND: Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood. METHODS: Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery. RESULTS: Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI. CONCLUSIONS: We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.

Anesthesia characteristic of an algorithm of bupivacaine dose based on height in caesarean section under spinal anesthesia: a retrospective cohort study.

BACKGROUND: An algorithm of bupivacaine dose based on height is applied to reduce maternal hypotension in caesarean section under spinal anesthesia. This study is designed to further verify whether the algorithm of bupivacaine dose based on height is suitable. METHODS: The parturients were grouped according to height. The comparison of anesthesia characteristic among subgroups was carried out. The univariate and multivariate binary logistic regressions were executed to reanalyze the interference factor for the anesthesia characteristic. RESULTS: When the dose of bupivacaine was adjusted by using the height based dosing algorithm, except for weight (P < 0.05), other general data did not present statistical changes with height (P > 0.05); the incidences of complications, characteristics of sensory or motor block, quality of anesthesia and neonatal outcome were of no statistical difference among parturients with different heights (P > 0.05); the height, weight and body mass index were not related with maternal hypotension (P > 0.05). When the dose of bupivacaine is constant, except for weight and body mass index (P > 0.05), the height was the independent risk factor for maternal hypotension (P < 0.05). CONCLUSIONS: Except for weight and body mass index, the height has an influence on the bupivacaine dose. It is reasonable that the bupivacaine dose is adjusted by using this dosing algorithm based on height. TRIAL REGISTRATION: This study was registered at http://clinicaltrials.gov (13/04/2018, NCT03497364).

Effects of dulaglutide combined with insulin degludec on glucose fluctuations and appetite in type 2 diabetes.

Introduction: The aim of this study was to describe appetite and glucose fluctuation in type 2 diabetes mellitus patients initiating treatment with dulaglutide combined with insulin degludec. Methods: This retrospective study of patients identified adults starting treatment with once-weekly (QW) dulaglutide combined with insulin degludec (experimental group) or insulin degludec alone (control group). Patients were followed for up to 6 months from treatment initiation. The clinical characteristics of patients, treatment patterns, CGM data, and appetite scores were obtained for the two groups. Results: A total of 236 patients were included in this study. SDBG, MAGE, LAGE, and PPGE of the experimental group were lower than the control group's (P < 0.05). The proportions of patients achieving a time in range (TIR) of ≥70% in the experimental group were higher than in the control group, with 43% and 10% on the second day, 88% and 47% on the fourth day, 95% and 47% on the seventh day, and 100% and 67% on the tenth day, respectively. Significant associations existed between TIR and the prevalence of islet function. At six months, 89.2% of patients in the experimental group were still using dulaglutide. Appetite decreased significantly at 1 week and increased at 3 months after treatment with dulaglutide. Conclusion: Dulaglutide combined with insulin degludec significantly reduces glucose fluctuations in patients with type 2 diabetes mellitus and improves the TIR rate. However, the treatment on appetite could decrease in the first three months.

Fingolimod (FTY720) Hinders Interferon-γ-Mediated Fibrotic Scar Formation and Facilitates Neurological Recovery After Spinal Cord Injury.

Following spinal cord injury (SCI), fibrotic scar inhibits axon regeneration and impairs neurological function recovery. It has been reported that T cell-derived interferon (IFN)-γ plays a pivotal role in promoting fibrotic scarring in neurodegenerative disease. However, the role of IFN-γ in fibrotic scar formation after SCI has not been declared. In this study, a spinal cord crush injury mouse was established. Western blot and immunofluorescence showed that IFN-γ was surrounded by fibroblasts at 3, 7, 14, and 28 days post-injury. Moreover, IFN-γ is mainly secreted by T cells after SCI. Further, in situ injection of IFN-γ into the normal spinal cord resulted in fibrotic scar formation and inflammation response at 7 days post-injection. After SCI, the intraperitoneal injection of fingolimod (FTY720), a sphingosine-1-phosphate receptor 1 (S1PR1) modulator and W146, an S1PR1 antagonist, significantly reduced T cell infiltration, attenuating fibrotic scarring via inhibiting IFN-γ/IFN-γR pathway, while in situ injection of IFN-γ diminished the effect of FTY720 on reducing fibrotic scarring. FTY720 treatment inhibited inflammation, decreased lesion size, and promoted neuroprotection and neurological recovery after SCI. These findings demonstrate that the inhibition of T cell-derived IFN-γ by FTY720 suppressed fibrotic scarring and contributed to neurological recovery after SCI.

Zearalenone regulates microRNA156 to affect the root development of Tetrastigma hemsleyanum.

Zearalenone (ZEN) is a secondary metabolite from Fusarium species. It is also present in plants and regulates the photochemical reaction in Photosystem II, the stress response and root growth. To investigate the mechanism by which ZEN regulates Tetrastigma hemsleyanum root growth, differentially expressed microRNAs (miRNAs) were identified and verified by high-throughput sequencing and Agrobacterium rhizogenes-mediated transformation of the roots of T. hemsleyanum seedlings treated with and without ZEN. The predicted functions of microRNA156b (miR156b) and microRNA156f (miR156f) were confirmed in transgenic hairy roots. (i) A total of 70 miRNAs showed significantly different expression levels under ZEN treatment, including seven highly conserved miRNAs. (ii) The number of lateral roots and total root length of the transgenic hairy roots overexpressing miR156b and miR156f was significantly higher than the wild-type hairy roots, and thus the overexpression of miR156b and miR156f in T. hemsleyanum promoted lateral root development. (iii) Bioinformatics analysis predicted that the target genes of miR156b and miR156f were SPL9/10. As compared with the wild-type hairy roots, the expression of SPL9 was significantly lower in the hairy roots overexpressing miR156b, and the expression of SPL10 was significantly lower in the hairy roots overexpressing miR156f. Therefore, SPL9 could be the target gene of miR156b, and SPL10 could be the target gene of miR156f. This study shows that ZEN could increase the expression of miR156b and miR156f in T. hemsleyanum roots, which negatively regulated the expression of their putative target genes SPL9 and SPL10, consequently promoting the growth and development of the lateral roots.

Idarubicin-loaded biodegradable microspheres enhance sensitivity to anti-PD1 immunotherapy in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary hepatocellular carcinoma (HCC). However, conventional TACE formulations such as epirubicin-lipiodol emulsion are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, we used biodegradable Idarubicin loaded microspheres (BILMs), which were prepared from gelatin and carrageenan and could be loaded with Idarubicin (IDA-MS). The morphology and the ability to load and release IDA of BILMs were characterized in vitro. We evaluated tumor changes and side effects after TACE treatment with IDA-MS in VX2 rabbit and C57BL/6 mice HCC models. In addition, the effect of IDA-MS on the tumor immune microenvironment of HCC tumors was elucidated via mass spectrometry and immunohistochemistry. Result showed that IDA-MS was developed as a new TACE formulation to overcome the poor delivery of drugs due to rapid elimination of the anticancer drug into the systemic circulation. We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment. STATEMENT OF SIGNIFICANCE: Conventional transarterial chemoembolization (TACE) formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in hepatocellular carcinoma (HCC). To overcome these limitations, we used biodegradable microspheres called BILMs, which could be loaded with Idarubicin (IDA-MS). We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment.

Antihypertension effect of astragaloside IV during cerebral ischemia reperfusion in rats.

Stroke is one of the leading causes of death from diseases. When the blood supply to the brain tissue is interrupted, neuronal core death occurs due to the lack of glucose and oxygen in min. Blood pressure lowering after ischemic stroke was proven to be an effective strategy to achieve neurovascular protection and reduce the risk of recurrent stroke. Astragaloside IV is a pure small molecular compound isolated from Radix Astragali, and it is well documented that astragaloside IV has neuroprotective effect on cerebral ischemia reperfusion (CIR) injury through many mechanisms, including antioxidant, anti­inflammatory and anti­apoptotic. The present study adopted mean arterial pressure (MAP) monitoring, neurological scoring, 2,3,5­triphenyltetrazolium chloride staining, enzyme­linked immuno­sorbent assay, western blotting and other experimental methods to investigate the effect of astragaloside IV on systemic blood pressure during CIR in a middle cerebral artery occlusion animal model. It was demonstrated that astragaloside IV pretreatment significantly alleviated CIR injury as previously reported. In addition, the elevation of MAP during CIR was significantly inhibited by astragaloside IV administration. Moreover, it was revealed that the expression of Na+­K+­2Cl­ cotransporter isoform 1 in the hypothalamus was inhibited and the subsequent synthesis of vasopressin was reduced by astragaloside IV pretreatment in the CIR animal model. In conclusion, astragaloside IV may alleviate CIR injury partially by lowering systemic blood pressure.

Characteristic analysis of skin keratinocytes in patients with type 2 diabetes based on the single-cell levels.

BACKGROUND: Keratinocytes play an important role in wound healing; however, less is known about skin keratinocytes in patients with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to search for the transcriptional characteristics of keratinocytes at the single-cell level from T2DM patients, and to provide experimental data for identifying the pathological mechanisms of keratinocytes under pathological conditions. METHODS: We performed single-cell RNA sequencing on the skin tissue from two T2DM patients and one patient without diabetes-induced trauma using the BD Rhapsody™ Single-Cell Analysis System. With the help of bioinformatics R-based single-cell analysis software, we analyzed the results of single-cell sequencing to identify the single-cell subsets and transcriptional characteristics of keratinocytes at the single-cell level, including Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyzes. RESULTS: In this study, we found specific highly expressed signature keratinocyte-related genes. We analyzed the transcriptome of keratinocytes from experimental and control groups and screened a total of 356 differential genes, which were subject to bioinformatics analysis. Enriched pathways included oxidative phosphorylation, antigen processing and presentation, prion and Huntingtons' diseases, bacterial invasion of epithelial cells, thermogenesis, vasopressin-regulated water reabsorption, and protein processing in the endoplasmic reticulum. CONCLUSIONS: This study revealed the characteristics of keratinocytes at the single-cell level and screened a group of differentially expressed genes related to T2DM-associated keratinocytes, oxidative phosphorylation, cytokine receptor interactions, prion diseases, and other signaling pathways.

Corrigendum: TAZ induces migration of microglia and promotes neurological recovery after spinal cord injury.

[This corrects the article DOI: 10.3389/fphar.2022.938416.].

Pachymic acid alleviates experimental pancreatic fibrosis through repressing NLRP3 inflammasome activation.

Pachymic acid (PA), a natural triterpenoid, possesses the capacity to repress inflammatory and profibrotic responses. However, the role of PA in pancreatic fibrosis remains unclear. Here the effect of PA on anti-fibrogenic response was investigated using in vivo and in vitro pancreatitis models. We demonstrated that PA treatment repressed TGF-ß-induced pancreatic stellate cells (PSCs) activation in vitro, as evidenced by decreased expression of Collagen I, α-smooth muscle actin, and fibronectin. PA decreased Cerulein-induced acinar injury and pancreatic fibrosis in an experimental pancreatitis model. Mechanistically, PA repressed Cerulein or (TGF-ß)-induced activation of nuclear factor (NF)-κB signaling and thus decreased NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome activation in PSCs. Pharmacological inhibition of NLRP3 repressed TGF-ß-induced activation of PSCs. More important, NLRP3 activator partially attenuated the effect of PA on inhibiting PSCs activation. Collectively, these data demonstrate that PA represses PSCs activation and pancreatic fibrosis through repressing NF-κB/NLRP3 signaling.

TAZ Induces Migration of Microglia and Promotes Neurological Recovery After Spinal Cord Injury.

Following spinal cord injury (SCI), microglia gradually migrate to the edge of the lesion, interweaving around the border of the lesion to form the microglial scar, which performs inflammatory limiting and neuroprotective functions. Recent reports showed that Yes-associated protein (YAP) was expressed in astrocytes and promoted the formation of astrocytic scars, while YAP was not expressed in microglia after SCI. YAP and its paralogue transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, which have a similar functional role as both are negatively regulated by the Hippo signalling pathway. However, the expression and function of TAZ after SCI are unclear. Our research group previously found that Fascin-1 was highly expressed in microglia and promoted migration of microglia after SCI, and that, there was a close regulatory relationship between Fascin-1 and YAP/TAZ. In this study, we demonstrated that TAZ was significantly upregulated and mainly expressed in microglia after SCI, and accumulated in the nuclei of microglia in the spinal cord at 14 days post-SCI. Moreover, TAZ was upregulated and accumulated in the nuclei of anti-inflammatory M2-like (M2-L) polarized or myelin-treated microglia. Additionally, XMU-MP-1 (an inhibitor of the Hippo kinase MST1/2 to active TAZ) promoted the aggregation of microglia around the lesion core, resulting in the formation of microglial scars and the functional recovery of mice after SCI. Our findings also indicated that TAZ promoted microglial migration in vitro. Mechanistically, Fascin-1 interacted with TAZ, which upregulated TAZ expression and induced TAZ nuclear accumulation in microglia to promote microglial migration. These findings revealed that TAZ mediated microglial migration to the edge of the lesion core, promoting the formation of microglial scars and functional recovery after SCI. Moreover, TAZ was downstream of Fascin-1, which positively regulated microglial migration after SCI.

Transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2: A systematic review and meta-analysis of secondary attack rate and asymptomatic infection.

BACKGROUND: Understanding the transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for control policies, but evidence remains limited. METHODS: We presented a systematic and meta-analytic summary concerning the transmissibility and pathogenicity of COVID-19. RESULTS: A total of 105 studies were identified, with 35042 infected cases and 897912 close contacts. 48.6% (51/105) of studies on secondary transmissions were from China. We estimated a total SIR of 7.8% (95% confidence interval [CI], 6.8%-8.8%), SAR of 6.6% (95% CI, 5.7%-7.5%), and symptomatic infection ratio of 86.9% (95%CI, 83.9%-89.9%) with a disease series interval of 5.84 (95%CI, 4.92-6.94) days. Household contacts had a higher risk of both symptomatic and asymptomatic infection, and transmission was driven between index cases and second-generation cases, with little transmission occurring in second-to-later-generation cases (SIR, 12.4% vs. 3.6%). The symptomatic infection ratio was not significantly different in terms of infection time, generation, type of contact, and index cases. CONCLUSIONS: Our results suggest a higher risk of infection among household contacts. Transmissibility decreased with generations during the intervention. Pathogenicity of SARS-CoV-2 varied among territories, but didn't change over time. Strict isolation and medical observation measures should be implemented.

Immunoproteomic analysis of the sporozoite antigens of Eimeria necatrix.

Eimeria necatrix, an apicomplexan protozoa of the genus Eimeria, causes intestinal coccidiosis that can reduce growth performance of poultry and result in high mortality in older chickens. In this report, the whole sporozoite proteins of E.necatrix were studied by two-dimensional electrophoresis (2-DE) and Western blotting using hyper-immune chicken serum containing E.necatrix-specific antibodies. Approximately 680 protein spots for E.necatrix sporozoite were detected by 2-DE with silver staining, where 98 spots were cross-reacted with the E. necatrix-specific immune sera. Out of the 56 spots that were selected for MALDI-TOF-MS/MS analysis, 50 unique proteins were identified using the MASCOT software, 8 proteins were identified as known E.necatrix proteins and the rest were all putative proteins. These proteins have a wide range of known or predicted structures, cellular locations and functions, including proteins in category nuclear location & function, multifunctional- or multifunctional motifs-containing proteins, cellular transport and structure-related proteins, proteins of enzymatic activities, motor proteins-related, cell surface and organelle-related proteins. These new findings will enhance our understandings of parasite immunogenicity and immune evasion mechanisms of E. necatrix and facilitate the discovery phase of highly effective vaccine candidates.

Delays in routine childhood vaccinations and their relationship with parental vaccine hesitancy: a cross-sectional study in Wuxi, China.

OBJECTIVES: This study aimed to examine childhood vaccination delay, explore the association between vaccination delay and parental vaccine hesitancy, and assess childhood vaccination delays during the coronavirus disease (COVID)-19 pandemic in China. METHODS: This cross-sectional survey was conducted in Wuxi City. Participants were recruited from local vaccination clinics. Questionnaires were used to collect information about socio-demographics, vaccine hesitancy, and immunization clinic evaluations. Vaccination records were obtained from the Jiangsu Information Management System of Vaccination Cases. RESULTS: Overall, 2728 participants were included. The coverage for seven category A vaccines (Expanded Program on Immunization (EPI)) was more than 95% at 24 months. The proportion of children vaccinated in a timely manner was the highest for the first dose of the hepatitis B vaccine (91.6%) and the lowest for the Bacillus-Calmette-Guerin vaccine (44.6%). More than 50% of the planned vaccinations were delayed in February and March 2020. The Vaccine Hesitancy Scale scores were not associated with vaccination delay (P = 0.842). Children's vaccination delays were negatively associated with parents who reported convenient access to clinics and satisfaction with immunization services (P = 0.020, P = 0.045). CONCLUSIONS: EPI is highly successful in China. Despite vaccination delays due to the COVID-19 pandemic, coverage was recovered after lockdown restrictions were eased.

Screening rate and influential factors of lung cancer with low-dose computed tomography in Asian population: a systematic review and meta-analysis.

BACKGROUND: There are currently no studies synthesizing the screening rate and influential factors of low-dose computed tomography (LDCT)-screened lung cancer in Asian population. METHODS: A systematic review was conducted, using both English and Chinese language databases on March, 2019. The pooled screening rate and estimated odds ratios (ORs) of influential factors were analyzed using random effects models. Subgroup and meta-regression analyses were also employed to explore the heterogeneity. RESULTS: The pooled LDCT lung cancer screening rate was 1.12% (95% confidence interval (CI): 0.94%, 1.32%), and increased with age. Adenocarcinoma and stage I lung cancer had higher screening rates. Analysis of influential factors in the general population showed that female and elder age (≥50 years) were significantly influencing LDCT lung cancer screening rate (for female, OR = 1.32, 95% CI: 1.15-1.52; for adults ≥ 50 years, OR = 1.94, 95% CI: 1.52-2.49). Meta-regression analysis indicated that the heterogeneity maybe significantly correlated with the sample size, risk population and source of population. CONCLUSIONS: Unlike European and American populations, female and adults > 50 years rather than smoking adults were positively associated with screening rate in Asian populations. It is important to further study the benefits of lung cancer screening with LDCT in Asian populations.

Influence of contest on Chinese college students' health literacy based on repeated cross-sectional studies.

Objective: Chinese college students' level of health literacy is low, so, we explored the effect of knowledge contests on health literacy (HL) among Chinese college students. Participants: Students from universities in Jiangsu, China. Methods: Two repeated cross-sectional studies were used to compare the effects of the college students' contests. Chi-square tests and variance analysis were used to compare the HL levels and scores, respectively; logistic regression was used for multivariate analysis. Results: The levels of HL after each contest were significantly higher than those in the baseline survey (p < .05). There were statistically significant score differences (p = .023 and p = .001) after the contests in the two studies. Multivariable analysis of HL contest showed that school, grade, profession, completion time, and contest history were statistically significant. Conclusions: HL among Chinese college students was low and it is helpful to regularly hold health knowledge contests to improve these levels, especially for most non-medical students.

Influencing factors of lung cancer in nonsmoking women: systematic review and meta-analysis.

BACKGROUND: Epidemiological studies have shown that some factors other than smoking may affect the risk of lung cancer in women, but the results are controversial. We conducted a meta-analysis to summarize the influencing factors of lung cancer in nonsmoking women. METHODS: Both English and Chinese databases were searched for publications from 1990 to 2020. All included studies were assessed according to the Newcastle-Ottawa Scale (NOS). The pooled odds ratios (ORs) and 95% confidence interval (CI) of influential factors were analyzed using the meta-analysis method, and the publication bias and sensitivity were analyzed. RESULTS: Among the five categories, the pooled OR of cooking factors category was the highest. Among 42 influencing factors, there were frequent fried food (OR = 2.42, 95% CI: 1.73-3.38) and long menstrual cycle (0.54, 95% CI: 0.39-0.75). A positive association of history of lung diseases/family lung/all cancer with lung cancer among Asian nonsmoking women (1.82, 95% CI: 1.60-2.07). Unlike other regions, cooking factors were the main risk factor for lung cancer in Asian. CONCLUSION: The meta-analysis suggests that cooking habits, diet, passive smoking, history of cancer and lung disease, and female reproduction are related to lung cancer in nonsmoking women. However, additional studies are warranted to extend this finding.

Reporting and Performance of Hepatocellular Carcinoma Risk Prediction Models: Based on TRIPOD Statement and Meta-Analysis.

Background: The performance of risk prediction models for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) was uncertain. The aim of the study was to critically evaluate the reports of transparent and external validation performances of these prediction models based on system review and meta-analysis. Methods: A systematic search of the Web of Science and PubMed was performed for studies published until October 17, 2020. The transparent reporting of a multivariable prediction model for the individual prognosis or diagnosis (TRIPOD) tool was used to critically evaluate the quality of external validation reports for six models (CU-HCC, GAG-HCC, PAGE-B, mPAGE-B, REACH-B, and mREACH-B). The area under the receiver operator characteristic curve (AUC) values was to estimate the pooled external validating performance based on meta-analysis. Subgroup analysis and metaregression were also performed to explore heterogeneity. Results: Our meta-analysis included 22 studies published between 2011 and 2020. The compliance of the included studies to TRIPOD ranged from 59% to 90% (median, 74%; interquartile range (IQR), 70%, 79%). The AUC values of the six models ranged from 0.715 to 0.778. In the antiviral therapy subgroups, the AUC values of mREACH-B, GAG-HCC, and mPAGE-B were 0.785, 0.760, and 0.778, respectively. In the cirrhosis subgroup, all models had poor discrimination performance (AUC < 0.7). Conclusions: A full report of calibration and handling of missing values would contribute to a greater improvement in the quality of external validation reports for CHB-related HCC risk prediction. It was necessary to develop a specific HCC risk prediction model for patients with cirrhosis.

The transcriptional characteristics of mast cells derived from skin tissue in type 2 diabetes patients at the single-cell level.

OBJECTIVES: The mechanisms underlying the role of mast cells in wound healing have not been thoroughly studied, and even fewer data are available on studies related to mast cells in the skin of patients with type 2 diabetes mellitus (T2DM). Therefore, this study aims to explore the transcriptional characteristics of mast cells at the single-cell level in patients with T2DM and provide experimental data for studying mast cell behaviors under abnormal glucose metabolism. METHODS: Two patients with T2DM and one trauma patient without diabetes were enrolled. Samples were derived from skin tissue resected at the time of surgery and were isolated by single cell capture technology on BD platform to prepare single cell cDNA library. Seurat was used to process raw reads and analyze data downstream of single-cell RNA sequencing, including removal of low-quality cells, identification of cell clusters at the single-cell level, and screening for differential genes with fold change > 1.5 and p < 0.05 by two-sided t-test. We performed single-cell RNA sequencing on skin tissues of T2DM patients and non-diabetics and identified the cell cluster of skin, single-cell subsets, and transcriptional characteristics of mast cells at a single-cell level. Meanwhile, gene set enrichment(GSEA) analysis was performed on the differentially expressed genes. RESULTS: A total of 8888 cells were obtained from skin tissue. Clustering analysis revealed eight-cell clusters, identified as smooth muscle cells, dendritic cells, mast cells, and T cells, respectively. Cluster 6 was identified as mast cells with the marker genes TPSAB1, CPA3, TPSB2, MS4A2,KIT, etc., which accounting for 2.7% of the total cell number.Compared with the control group, the genes highly expressed in MCs from T2DM patients, include ADH1C, PAXIP1, HAS1, ARG1, etc., and the low expression genes include PHACTR2, GGA1, RASSF2, etc. GSEA analysis suggested that the signal pathways of MCS in T2DM patients included VEGF signaling pathway, Fc gamma R-mediated phagocytosis, the B cell receptor signaling pathway, natural killer cell-mediated cytotoxicity. CONCLUSIONS: The characteristic genes of MCs in the skin tissues of T2DM patients were described at the single-cell level. These genes and enriched signaling pathways provide a theoretical basis and data support for further researches on dermatopathy in patients with diabetes mellitus.

Economic evaluation of varicella vaccination strategies in Jiangsu province, China: a decision-tree Markov model.

This study evaluated different varicella vaccination strategies in Jiangsu province, China. A decision-tree Markov model was used to evaluate the cost effectiveness of various varicella vaccination strategies for children, including direct and selective vaccination (serotesting pre-vaccination). A cohort of one-year-old children was followed through 60 one-year Markov cycles. The parameter estimation was based on field work, the literature, and statistical yearbooks. We calculated the incremental cost-utility ratio (ICUR) using the saved quality-adjusted life year (QALY). One-way and probability sensitivity analyses were performed to assess uncertainty. Among 100,000 cohort members, one-dose and two-dose direct vaccination averted 8061 and 10,701 varicella cases, respectively, compared with no vaccination. Furthermore, compared with no vaccination, one-dose and two-dose direct vaccination saved one QALY at the ICUR of USD 21,401.33 and USD 35,420.81, respectively, at less than three times the per capita gross domestic product (USD 47,626.86) of Jiangsu. The ICURs of the one-dose and two-dose selective strategies versus no vaccination were USD 42,623.62 and USD 51,406.35 per QALY gained, respectively. The cost effectiveness results were most sensitive to the QALY loss of outpatients and vaccine prices. Thus, in Jiangsu, one-dose and two-dose direct varicella vaccination in children could be cost effective at the willingness to pay threshold of three times provincial GDP per capita from a societal perspective. The findings were sensitive to the vaccine price and health utility of varicella cases.