Reversing Metabolic Dysfunction-Associated Steatotic Liver Disease Promotes Healthy Pediatric Cardiovascular Structures: The PROC Study.

INTRODUCTION: We investigated the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on cardiovascular structure development in children. METHODS: We followed 1,356 children with the mean age of 6.6 years for 4.5 years in Beijing, China. We assessed the association of MASLD with cardiovascular structure (carotid intima-media thickness and left ventricular mass) outcomes at baseline and follow-up. RESULTS: Over follow-up, 59 children had persistent MASLD, 109 had incident MASLD (progression), and 35 had normalization of liver health. Children with MASLD normalization showed a significantly lower mean development in carotid intima-media thickness (0.161 vs 0.188 mm) and left ventricular mass (4.5 vs 12.4 g) than children with persistent MASLD. DISCUSSION: The control of MASLD was associated with improved cardiovascular structure development.

EMP3 as a prognostic biomarker correlates with EMT in GBM.

BACKGROUND: Glioblastoma (GBM) is the most aggressive malignant central nervous system tumor with a poor prognosis.The malignant transformation of glioma cells via epithelial-mesenchymal transition (EMT) has been observed as a main obstacle for glioblastoma treatment. Epithelial membrane protein 3 (EMP3) is significantly associated with the malignancy of GBM and the prognosis of patients. Therefore, exploring the possible mechanisms by which EMP3 promotes the growth of GBM has important implications for the treatment of GBM. METHODS: We performed enrichment and correlation analysis in 5 single-cell RNA sequencing datasets. Differential expression of EMP3 in gliomas, Kaplan-Meier survival curves, diagnostic accuracy and prognostic prediction were analyzed by bioinformatics in the China Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) database. EMP3-silenced U87 and U251 cell lines were obtained by transient transfection with siRNA. The effect of EMP3 on glioblastoma proliferation was examined using the CCK-8 assay. Transwell migration assay and wound healing assay were used to assess the effect of EMP3 on glioblastoma migration. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to detect the mRNA and protein expression levels of EMT-related transcription factors and mesenchymal markers. RESULTS: EMP3 is a EMT associated gene in multiple types of malignant cancer and in high-grade glioblastoma. EMP3 is enriched in high-grade gliomas and isocitrate dehydrogenase (IDH) wild-type gliomas.EMP3 can be used as a specific biomarker for diagnosing glioma patients. It is also an independent prognostic factor for glioma patients' overall survival (OS). In addition, silencing EMP3 reduces the proliferation and migration of glioblastoma cells. Mechanistically, EMP3 enhances the malignant potential of tumor cells by promoting EMT. CONCLUSION: EMP3 promotes the proliferation and migration of GBM cells, and the mechanism may be related to EMP3 promoting the EMT process in GBM; EMP3 may be an independent prognostic factor in GBM.

Size-Controlled Silver Nanoparticles Supported by Pyrolytic Carbon from Microcrystalline Cellulose.

A facile method was developed for preparing size-controlled silver nanoparticles supported by pyrolytic carbon from microcrystalline cellulose (MCC). The pyrolysis of cellulose-AgNO3 mixture caused the oxidation of cellulose, resulting in carboxyl groups to which silver ions can bind firmly and act as nuclei for the deposition of silver nanoparticles. The structure and properties of the obtained nanocomposite were characterized by using a scanning electron microscope (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). The results suggest that silver nanoparticles were integrated successfully and dispersed uniformly in the pyrolytic carbon matrix. The average particle size varied between 20 nm and 100 nm in correlation to the dose of silver nitrate and temperature of pyrolysis. The products showed high electric conductivity and strong antimicrobial activity against Escherichia coli (E. coli).

COVID-19 Clinical Presentation Among HIV-Infected Persons in China: A Systematic Review.

PURPOSE OF REVIEW: The impact of HIV infection on the natural history of COVID-19 is unknown, given the recency of the human spread of SARS-CoV-2 (CoV). We reviewed published case series/reports of CoV-HIV coinfections to clarify epidemiologic and clinical features in China, the first nation with pandemic experience. RECENT FINDINGS: Assuming that HIV-infected persons were at average risk of CoV infection in Wuhan, we estimated HIV-CoV coinfected persons to number 412 (95%CI: 381-442); our review encompassed an estimated 16.7% (69/412) of Wuhan. Men (many of whom reported sex with other men) accounted for 71.1% (54/76) of the cases reported in China. The median age was 48.0 years old (range 24-77, interquartile:37-57). The median CD4+ cell count at the last clinical visit was 421 cells/µL; 83.0% had an undetectable viral load. Among 31 patients with clinical details reported, fatigue (41.9%), respiratory distress (41.9%), and gastrointestinal symptoms (26.7%) were most common. Among the 52 cases reporting COVID-19 clinical severity, 46.2% were severe, 44.2% mild, and 9.6% asymptomatic COVID-19. Late antiretroviral therapy (ART) was reported by 30.4% (7/23) among whom 57.1% (4/7) were confirmed as severe COVID-19. The case fatality rate was 9.1% (3/33). Severe disease and death were less common among persons who took ART prior to the COVID-19 diagnosis. Of 16 reported IL-6 results, 68.7% were within the normal range. Earlier use of ART was associated with a better COVID-19 prognosis with CoV-HIV co-infection reported from China through early 2021, but small sample sizes limit definitive conclusions.

Landscape of associations between long non-coding RNAs and infiltrating immune cells in liver hepatocellular carcinoma.

Liver hepatocellular carcinoma (LIHC) can be detected by the immune system; however, it acquires features for evasion of immune surveillance during its origin and development. Long non-coding RNAs (lncRNAs) are critical as immune regulators in cancers; nevertheless, the biological functions and mechanisms of lncRNAs in evasion of immune system by LIHC remain unclear. In this study, an integrated and computational approach was developed to identify immune-related lncRNAs and to divide LIHC patients into diverse immune-related risk groups based on the expression profiles of coding genes and lncRNAs. LIHC-specific genes and lncRNAs in 17 immune cell populations were identified and analysed. Gene and lncRNA co-expressing networks for diverse immune cell populations were constructed and analysed. Some imported immune-related lncRNAs, such as MIR9-3HG, were also identified. The LIHC patients comprised three different groups based on immune-related risk. LIHC patients possessing a greater diversity of immune cell populations had better survival prognosis. The collective data are evidence of a credible computational model that can prioritize novel immune-related lncRNAs and depict the atlas of immune-related lncRNAs in LIHC. These findings will further the understanding of lncRNA function and advance the identification of immunotherapy targets in LIHC.

Very-Low-Dose Decitabine Is Effective in Treating Intermediate- or High-Risk Myelodysplastic Syndrome.

Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months, 10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and 3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%. Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed among all courses. The median cost of each course was USD 5,300, 3,000, 2,900, and 2,000, respectively. Multivariate analysis identified bone marrow blast cells ≥10% and a Charlson comorbidity index ≥1 as 2 independent factors for efficacy. In conclusion, very-low-dose decitabine showed relatively good efficacy, good tolerance, and low medical cost in the treatment of intermediate- or high-risk MDS. Elderly patients with more than 1 complication or patients with a higher proportion of blast cells may be the most suitable candidates for this regimen.

Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder with heterogeneous clinical, morphological and genetic characteristics. Clonal cytogenetic abnormalities are found in 20-30% of patients with CMML. Patients with low risk cytogenetic features (normal karyotype and isolated loss of Y chromosome) account for ∼80% of CMML patients and often fall into the low risk categories of CMML prognostic scores. We hypothesized that single nucleotide polymorphism arrays (SNP-A) karyotyping could detect cryptic chromosomal alterations with prognostic impact in these subgroup of patients. SNP-A were performed at diagnosis in 128 CMML patients with low risk karyotypes or uninformative results for conventional G-banding cytogenetics (CC). Copy number alterations (CNAs) and regions of copy number neutral loss of heterozygosity (CNN-LOH) were detected in 67% of patients. Recurrent CNAs included gains in regions 8p12 and 21q22 as well as losses in 10q21.1 and 12p13.2. Interstitial CNN-LOHs were recurrently detected in the following regions: 4q24-4q35, 7q32.1-7q36.3, and 11q13.3-11q25. Statistical analysis showed that some of the alterations detected by SNP-A associated with the patients' outcome. A shortened overall survival (OS) and progression free survival (PFS) was observed in cases where the affected size of the genome (considering CNAs and CNN-LOHs) was >11 Mb. In addition, presence of interstitial CNN-LOH was predictive of poor OS. Presence of CNAs (≥1) associated with poorer OS and PFS in the patients with myeloproliferative CMML. Overall, SNP-A analysis increased the diagnostic yield in patients with low risk cytogenetic features or uninformative CC and added prognostic value to this subset of patients.

BRCC3 mutations in myeloid neoplasms.

Next generation sequencing technologies have provided insights into the molecular heterogeneity of various myeloid neoplasms, revealing previously unknown somatic genetic events. In our cohort of 1444 cases analyzed by next generation sequencing, somatic mutations in the gene BRCA1-BRCA2-containing complex 3 (BRCC3) were identified in 28 cases (1.9%). BRCC3 is a member of the JAMM/MPN+ family of zinc metalloproteases capable of cleaving Lys-63 linked polyubiquitin chains, and is implicated in DNA repair. The mutations were located throughout its coding region. The average variant allelic frequency of BRCC3 mutations was 30.1%, and by a serial sample analysis at two different time points a BRCC3 mutation was already identified in the initial stage of a myelodysplastic syndrome. BRCC3 mutations commonly occurred in nonsense (n=12), frameshift (n=4), and splice site (n=5) configurations. Due to the marginal male dominance (odds ratio; 2.00, 0.84-4.73) of BRCC3 mutations, the majority of mutations (n=23; 82%) were hemizygous. Phenotypically, BRCC3 mutations were frequently observed in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms and associated with -Y abnormality (odds ratio; 3.70, 1.25-11.0). Clinically, BRCC3 mutations were also related to higher age (P=0.01), although prognosis was not affected. Knockdown of Brcc3 gene expression in murine bone marrow lineage negative, Sca1 positive, c-kit positive cells resulted in 2-fold more colony formation and modest differentiation defect. Thus, BRCC3 likely plays a role as tumor-associated gene in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.

Peripheral T-cell subsets in radiofrequency ablation for tumors from different origins.

BACKGROUNDS: Radiofrequency ablation (RFA) is known to destroy tumoral tissue and activate immune cells. This study aimed to investigate the impact of RFA on peripheral T-cell responses and its relationship with tumor origin and hepatitis status. METHODS: A retrospective analysis was conducted on 62 patients with various types of tumors, including hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, and others, who underwent RFA treatment between June 2017 and December 2018. Blood samples were collected before and one day after RFA treatment. The peripheral T-cell subsets were measured by flow cytometry, and their changes were analyzed. RESULTS: The study found a decrease in the CD4+CD8-and CD4-CD8+ T-cell subsets after RFA, but no significant changes were observed in the populations of CD4+CD8+ and the CD4+CD8-/CD4-CD8+ ratio. Furthermore, no significant differences were observed in peripheral T-cell subsets concerning tumor type or hepatitis status. CONCLUSIONS: The study suggests that RFA treatment may have a short-term impact on peripheral T-cell responses, characterized by a decrease in certain T-cell subsets. However, these changes do not seem to be related to the tumor type or hepatitis status of the patients.

Elevated expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP is a novel indicator for lymph node and peritoneal metastasis of epithelial ovarian cancer patients.

The present study aims to clarify whether hyaluronan binding protein 1 (HABP1/p32/C1QBP) is an indicator of peritoneal and lymph node metastasis in epithelial ovarian cancer (EOC), which to the authors' knowledge is not previously reported by others. Western blot analysis demonstrated that HABP1 was highly overexpressed in most metastatic lesions. Of 89 patients whose primary tumors showed high HABP1 expression on immunohistochemical staining, 85 (95.5%) presented peritoneal metastases and 43 (48.3%) had lymph node metastases. Univariate and multivariate logistic regression analyses revealed that HABP1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. The specificity and positive predictive value of HABP1 staining were shown to be better for peritoneal metastasis, while the negative and sensitivity predictive value of HABP1 staining were better for lymph node metastasis. The odds ratio of high versus low staining for peritoneal spread was 9.236 (95% confidence interval (CI), 2.705, 19.316), and that for lymph node metastasis was 8.614 (95% CI, 2.507, 21.039). Furthermore, HABP1 protein may potentially be used alone or in combination with other markers as a predictive marker of EOC patients with lymph node metastasis and/or peritoneal dissemination.

Spatiotemporal divergence and convergence test of green total factor productivity of grain in China: based on the dual perspective of carbon emissions and surface source pollution.

The topic of grain production and quality has always been a fundamental issue for the country's livelihood. With the purpose of contributing to high-quality grain development and ensuring national food security, this paper explores the spatial and temporal evolution, regional differences and convergence of grain green total factor productivity (GTFP) in the main grain-producing regions of China from the dual perspectives of carbon emissions and surface pollution with the help of EBM-GML model, kernel density function estimation and convergence methods. The results show that (1) Grain GTFP has generally shown a positive growth trend, although there exists obvious spatial differences. (2) In terms of decomposition indices, technological progress is the source of the increase in grain GTFP. (3) There are σ convergence, absolute ß convergence and conditional ß convergence in the main producing region as well as in the Yellow River basin and the Yangtze River basin; there are only absolute ß convergence and conditional ß convergence in the Songhua River basin. Grain GTFP has a single high-efficiency convergence point, and the grain GTFP is enhancing year by year in each province, and the inter-provincial gap is shrinking.

Sex-Specific Differences in Left Ventricular Mass and Volumes with Body Mass Index among Children Aged 6 to 8: A Cross-Sectional Study in China.

Few studies have examined the sex differences in left ventricle (LV) structure and physiology from early life stages. We aimed to assess the role of sex and overweight/obesity on left ventricular mass (LVM) and LV volume in Chinese children without preexisting cardiovascular risk factors. We selected 934 healthy children aged 6-8 years from an existing cohort in Beijing, China. Linear regression models were used to regress body mass index (BMI), fat mass, systolic blood pressure, diastolic blood pressure, waist circumference, and visceral fat area (VFA) with LVM, left ventricle end-diastolic volume (LVEDV) and end-systolic volume (LVESV). Higher BMI, fat mass, waist circumference, VFA, and stroke volume (SV) predicted higher LVM, LVEDV, and LVESV in both sexes. Multivariable analysis showed that boys with an elevated BMI had greater LV hypertrophy. LVEDV and LVESV were higher among boys than among girls and increased with higher BMI in both boys and girls. LVEDV and LVESV were associated with VFA in boys. We observed sex differences in LVM, LVESV, and LVEDV among prepubertal children, independent of obesity, with higher values observed in boys. Sex differences in cardiac structure in children may help explain the higher incidence of cardiovascular disease in male adults. Whether interventions to reduce childhood obesity can improve the trajectory of cardiac dynamics is worth investigating.

Good Adherence to the Mediterranean Diet Lowered Risk of Renal Glomerular Impairment in Children: A Longitudinal Study.

Healthy diet patterns have a positive effect on chronic non-communicable diseases in the pediatric population, but the evidence is limited on the association between kidney impairment and adherence to a Mediterranean diet. We aim to determine the associations between Mediterranean diet adherence and longitudinal tubular and glomerular impairment in children. Based on four waves of urine assays conducted from October 2018 to November 2019, we assayed urinary ß2-microglobulin (ß2-MG) and microalbumin (MA) excretion to determine transient renal tubular and glomerular impairment during the follow-up of the child cohort (PROC) study in Beijing, China. We assessed Mediterranean diet adherence using the 16-item Mediterranean Diet Quality Index in children and adolescents (KIDMED) among 1914 primary school children. Poor, intermediate, and good adherence rates for the Mediterranean diet were 9.0% (KIDMED index 0-3), 54.4% (KIDMED index 4-7) and 36.5% (KIDMED index 8-12), respectively. A short sleep duration was more prevalent in children with lower Mediterranean diet adherence, with no significant differences presenting in the other demographic and lifestyle covariates. The results of linear mixed-effects models showed that a higher urinary MA excretion was inversely associated with a higher KIDMED score (ß = -0.216, 95%CI: -0.358, -0.074, p = 0.003), after adjusting for sex, age, BMI z-score, SBP z-score, screen time, sleep duration and physical activity. Furthermore, in generalized linear mixed-effects models, consistent results found that transient renal glomerular impairment was less likely to develop in children with intermediate Mediterranean diet adherence (aOR = 0.68, 95%CI: 0.47, 0.99, p = 0.044) and in children with good Mediterranean diet adherence (aOR = 0.60, 95%CI: 0.40, 0.90, p = 0.014), taking poor Mediterranean diet adherence as a reference. We visualized the longitudinal associations between each item of the KIDMED test and kidney impairment via a forest plot and identified the main protective eating behaviors. Children who adhere well to the Mediterranean diet have a lower risk of transient glomerular impairment, underscoring the necessity of the early childhood development of healthy eating patterns to protect kidney health.

Interaction of Hydration Status and Physical Activity Level on Early Renal Damage in Children: A Longitudinal Study.

Background: Optimal water intake positively affects various aspects of human physiology, especially renal function. Physical activity (PA) may have an impact on hydration status and renal health, but the interaction of hydration status and PA level on renal function is not well-studied in children. Methods: We conducted four waves of urine assays in our child cohort (PROC) study from October 2018 to November 2019 in Beijing, China. We measured urinary specific gravity, ß2-microglobulin (ß2-MG), and microalbumin (MA) excretion to assess hydration status and renal damage in the context of PA level and other covariates among 1,914 primary school children. We determined the associations of renal damage with the interaction of hydration status and PA level using generalized linear mixed-effects models. Results: The prevalence of dehydration was 35.0%, 62.1%, 63.9%, and 63.3%, and the prevalence of insufficient PA was 86.2%, 44.9%, 90.4%, and 90.2% from wave 1 to wave 4 among 1,914 primary school children. From wave 1 to wave 4, the prevalence of renal tubular damage had a significant increasing trend of 8.8%, 15.9%, 25.7%, and 29.0% (Z = 16.9, P < 0.001), while the prevalence of glomerular damage revealed a declining trend of 5.6%, 5.5%, 4.4%, and 4.1% (Z = -2.4, P = 0.016). There were stable longitudinal associations of renal tubular and glomerular damage with hydration status (euhydration: OR = 0.50 and 0.33, respectively) but not with PA level. In multivariate analysis, significant interactions of hydration status and PA level were noted with renal tubular damage (ß = 0.43, P = 0.014) and glomerular damage (ß = 0.60, P = 0.047). Children with euhydration and insufficient PA were less likely to have renal tubular damage (OR = 0.46, 95% CI: 0.39, 0.53) or glomerular damage (OR = 0.28, 95% CI: 0.20, 0.39); children with euhydration and sufficient PA were also less likely to have renal tubular damage (OR = 0.57, 95% CI: 0.44, 0.75) or glomerular damage (OR = 0.47, 95% CI: 0.30, 0.74), adjusting for age, sex, BMI z-score, standardized SBP, sleep duration, computer/cell phone screen time, and fruit and vegetable intake. Conclusion: Children with euhydration and either sufficient or insufficient PA were less likely to have early renal damage. Adequate daily water intake for children is important, especially after PA.

An Algorithm for Solving the Phase Ambiguity Problem of SAW Delay-Line Sensor Systems.

Solving the phase ambiguity problem is crucial to achieving a wide-range and high-precision measurement for the frequency-domain sampling (FDS)-based surface acoustic wave (SAW) delay-line sensor systems. This study proposes an improved phase estimation algorithm called dual-band phase estimation (DBPE) to solve the problem. By using DBPE, the SAW sensor system can obtain an extensive and alterable measuring range without further requirements for sensor design or transmitted signals. Thus, it can be widely used in various FDS-based SAW delay-line sensor systems. Monte Carlo simulations and temperature measuring experiments, based on a YZ-cut LiNbO3 SAW delay-line sensor and a switched frequency-stepped continuous wave (S-FSCW) reader, are performed to demonstrate the algorithm's validity. The Monte Carlo simulations show that DBPE can effectively solve the phase ambiguity problem and has better performance than frequency estimation in measuring precision at a low signal-to-noise ratio (SNR). The temperature-sensing experiments show that DBPE has a good performance in measuring range and precision, serving as a phase ambiguity solver in the temperature sensor system.

Dehydration Status Aggravates Early Renal Impairment in Children: A Longitudinal Study.

Dehydration is common in children for physiological and behavioral reasons. The objective of this study was to assess changes in hydration status and renal impairment across school weekdays. We conducted a longitudinal study of three repeated measures of urinalysis within one week in November 2019 in a child cohort in Beijing, China. We measured urine specific gravity (USG) to determine the dehydration status, and the concentration of ß2-microglobulin (ß2-MG) and microalbumin (MA) to assess renal function impairment among 1885 children with a mean age of 7.7 years old. The prevalence of dehydration was 61.9%, which was significantly higher in boys (64.3%). Using chi-square tests and linear mixed-effects regression models, we documented the trends of the renal indicators' change over time among different hydration statuses. Compared to Mondays, there were apparent increases of ß2-MG concentrations on Wednesdays (ß = 0.029, p < 0.001) and Fridays (ß = 0.035, p < 0.001) in the dehydrated group, but not in the euhydrated group. As for the MA concentrations, only the decrease on Fridays (ß = -1.822, p = 0.01) was significant in the euhydrated group. An increased trend of elevated ß2-MG concentration was shown in both the euhydrated group (Z = -3.33, p < 0.001) and the dehydrated group (Z = -8.82, p < 0.001). By contrast, there was a decreased trend of elevated MA concentrations in the euhydrated group (Z = 3.59, p < 0.001) but not in the dehydrated group. A new indicator ratio, ß2-MG/MA, validated the consistent trends of renal function impairment in children with dehydration. Renal impairment trends worsened as a function of school days during the week and the dehydration status aggravated renal impairment during childhood across school weekdays, especially tubular abnormalities in children.

Sponge-like loose and porous SnO2 microspheres with rich oxygen vacancies and their enhanced room-temperature gas-sensing performance.

Structure and surface modification of semiconductor materials are of great importance in gas sensors. In this study, a facile citric acid-assisted solvothermal method via a precise calcination process was leveraged to synthesize sponge-like loose and porous SnO2 microspheres with rich oxygen vacancies (denoted as LP-SnO2-Ov). When this material was used in a gas sensor, it exhibited an extremely high response to 10 ppm hydrogen sulfide gas at room temperature (Ra/Rg = 9688), which was 54 times higher than that of commercial SnO2. Furthermore, the response time of LP-SnO2-Ov was 5 s, while the recovery time was 177 s. Moreover, it displayed such high selectivity and stability for hydrogen sulfide gas that its properties remained almost unchanged after 1 month. This method paves a new way to fabricate materials possessing a sponge-like loose and porous structure with oxygen vacancies, which is promising for many other scientific fields such as lithium-ion batteries and photocatalysis.

Immune characteristics of human immunodeficiency virus/severe acute respiratory syndrome coronavirus 2 coinfection: A case report and mini-review.

Since its first appearance in Wuhan, China, severe acute respiratory syndrome coronavirus 2 has rapidly spread throughout the world and has become a global pandemic. It remains unclear whether people living with human immunodeficiency virus are at an increased risk of coronavirus disease 2019 and severe disease manifestation; until now, the evidence regarding the outcomes from severe acute respiratory syndrome coronavirus 2 infection in people living with human immunodeficiency virus is still limited and conflicting. The clinical characteristics of seven patients of family cluster-onset coronavirus disease 2019 were reported, including the immune characteristics of one patient of human immunodeficiency virus/severe acute respiratory syndrome coronavirus 2 coinfection. In the patients of human immunodeficiency virus/severe acute respiratory syndrome coronavirus 2 coinfection, about 2 weeks after infection, it was observed that CD4 and CD8 count showed a downward trend and that of CD8 is more obvious; at the same time, lymphocytes showed a slight increase. CD4, CD8, and lymphocytes are in the plateau period from the second week to the fourth week. About 4 weeks after infection, all showed an increase, in which anti-coronavirus combined with antiviral therapy were given. The time for Nucleic Acid Testing to present as negative was 51 days. The other six patients in the family were non-human immunodeficiency virus infected, the familial cluster received parallel treatment, and the median time for the Nucleic Acid Testing to present as negative was 29 days. The patient of human immunodeficiency virus/severe acute respiratory syndrome coronavirus 2 coinfection presents an immune state of CD4's and CD8's dual lymphatic depletion. Human immunodeficiency virus should still be regarded as an important factor in future risk stratification models for coronavirus disease 2019.

Efficacy and Safety of Intrathecal Pemetrexed Combined With Dexamethasone for Treating Tyrosine Kinase Inhibitor-Failed Leptomeningeal Metastases From EGFR-Mutant NSCLC-a Prospective, Open-Label, Single-Arm Phase 1/2 Clinical Trial (Unique Identifier: ChiCTR1800016615).

INTRODUCTION: We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC. METHODS: Patients with EGFR-mutant NSCLC with LM who had failed tyrosine kinase inhibitors were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a phase 1 study. The recommended dose (RD) determined in phase 1 was used in the phase 2 study. The primary end point was treatment efficacy measured as the clinical response rate. Overall survival and adverse events (AEs) were evaluated as secondary end points. RESULTS: The RD observed in the phase 1 study was 50 mg pemetrexed. A total of 30 cases of LM-NSCLC were enrolled in the phase 2 study, including 14 males and 16 females. Four patients did not survive for 4 weeks and could not be evaluated for efficacy. The clinical response rate was 84.6% (22 of 26). The median overall survival of all patients was 9.0 months (n = 30, 95% confidence interval: 6.6-11.4 mo). Most AEs were mild, and the most frequent AE of any grade was myelosuppression (n = 9, 30%), which returned to normal after symptomatic treatment. CONCLUSIONS: This study revealed that 50 mg pemetrexed is the RD which results in few AEs and a good response rate. IP is an effective treatment for patients with EGFR-mutant NSCLC-LM who had failed on tyrosine kinase inhibitor.

Scutellarin promotes in vitro angiogenesis in human umbilical vein endothelial cells.

Angiogenesis is critical to a wide range of physiological and pathological processes. Scutellarin, a major flavonoid of a Chinese herbal medicine Erigeron breviscapus (Vant.) Hand. Mazz. has been shown to offer beneficial effects on cardiovascular and cerebrovascular functions. However, scutellarin's effects on angiogenesis and underlying mechanisms are not fully elucidated. Here, we studied angiogenic effects of scutellarin on human umbilical vein endothelial cells (HUVECs) in vitro. Scutellarin was found by MTT assay to induce proliferation of HUVECs. In scutellarin-treated HUVECs, a dramatic increase in migration was measured by wound healing assay; Transwell chamber assay found significantly more invading cells in scutellarin-treated groups. Scutellarin also promoted capillary-like tube formation in HUVECs on Matrigel, and significantly upregulated platelet endothelial cell adhesion molecule-1 at both mRNA and protein levels. Scutellarin's angiogenic mechanism was investigated in vitro by measuring expression of angiogenic factors associated with cell migration and invasion. Scutellarin strongly induced MMP-2 activation and mRNA expression in cultured HUVECs in a concentration-dependent manner. Taken together, these results suggest that scutellarin promotes angiogenesis and may form a basis for angiogenic therapy.