Long-term safety and influence on growth in patients receiving sirolimus: a pooled analysis.

BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

A new contingent screening strategy increased detection rate of trisomy 21 in the first trimester.

BACKGROUND: Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21. METHODS: This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care. RESULTS: When cut-off values of free beta subunit of human chorionic gonadotropin (free ß-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively. CONCLUSIONS: The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.

Voriconazole-Induced Hepatotoxicity in a Patient with Pulmonary Aspergillosis: A Case Report.

Voriconazole is the therapy of choice for aspergillosis. However, hepatotoxicity is the most common reason for the discontinuation of voriconazole. In contrast, posaconazole is well tolerated, with a low incidence of hepatotoxicity. In most cases, hepatotoxicity is associated with high voriconazole trough concentration influenced mainly by cytochrome P450 (CYP) 2C19 gene polymorphism. Compared with normal metabolizers, intermediate and poor metabolizers generally have higher voriconazole trough concentrations with an increased risk of hepatotoxicity. Here, we describe changes in hepatotoxicity throughout azole therapy in a patient with pulmonary aspergillosis (PA). Nevertheless, the patient with the normal metabolism genotype of CYP2C19 developed severe hepatotoxicity caused by voriconazole but tolerated posaconazole well, with a lack of direct cross-hepatotoxicity between the both. Interestingly, the patient had a high risk of hepatotoxicity at a low voriconazole trough concentration. Fortunately, elevated liver enzymes declined to the baselines with posaconazole treatment.

Case report: Mycobacterium neoaurum infection during ICI therapy in a hepatocellular carcinoma patient with psoriasis.

We report here a patient with advanced hepatocellular carcinoma (HCC) and psoriasis treated with immune checkpoint inhibitor (ICI) therapy who experienced tumor partial response and psoriatic exacerbation. Meanwhile, the patient contracted mycobacterium neoaurum during the treatment period, while it was an opportunistic infection and mainly happened in immunosuppressed patients. We discussed the possibility that this infection was an ICI-associated infection independent of immunosuppression due to dysregulated immunity, which was the result of the effects of immunotherapy and autoimmune disease (AID), and the characteristics and treatment of M. neoaurum, which was rarely reported in China. This case highlights the fact that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, especially the patients with AID.

Investigation of the Rheological Properties and Chemical Structure of Asphalt under Multiple Aging Conditions of Heat, UV and Aqueous Solution.

During the service period, asphalt materials are affected by various natural factors, including heat, ultraviolet light, oxygen and moisture, etc., resulting in the reduction of pavement performance, the increase of pavement distress and shortening of service life. This study aims to investigate the aging performance of asphalt under multiple aging conditions of heat, UV and aqueous solution. Thermal-oxygen aging, UV aging and hydrostatic erosion tests were carried out sequentially on asphalt. The rheological properties, chemical structure and element composition of asphalt were characterized before and after aging, and the effect mechanism of multiple conditions was discussed. The results show that the multiple conditions of heat and UV can increase the rutting resistance and weaken the cracking resistance of asphalt. However, the effect degree of UV decreases gradually with the deepening of aging degree. Additionally, the effect of water on the physicochemical properties is less than that of UV; however, water can increase the sensitivity of physicochemical properties to UV. In summary, this study explored the short-term cycling effect of heat, light and water on asphalt and provided an idea for simulation test of asphalt under multiple aging condition.

The Diagnostic Value of Mitochondrial Mass of Peripheral T Lymphocytes in Early Sepsis.

Background: Studies have shown that lymphocyte dysfunction can occur during the early stages of sepsis and that cell dysfunction is associated with mitochondrial dysfunction. Therefore, quantifying the mitochondrial function of lymphocytes in patients with sepsis could be valuable for the early diagnosis of sepsis. Methods: Seventy-nine patients hospitalized from September 2020 to September 2021 with Sepsis-3 were retrospectively analyzed and subsequently compared with those without sepsis. Results: Univariate analysis showed statistical differences between the data of the two groups regarding age, neutrophil/lymphocyte, procalcitonin (PCT), C-reactive protein, total bilirubin, serum creatinine, type B natriuretic peptide, albumin, prothrombin time, activated partial thromboplastin time, lactic acid, single-cell mitochondrial mass (SCMM)-CD3, SCMM-CD4, SCMM-CD8, and Acute Physiology and Chronic Health Evaluation II score (P < 0.05). Multivariate logistic regression analysis performed on the indicators mentioned above demonstrated a statistical difference in PCT, lactic acid, SCMM-CD4, and SCMM-CD8 levels between the two groups (P < 0.05). The receiver operating characteristic curves of five models were subsequently compared [area under the curve: 0.740 (PCT) vs. 0.933 (SCMM-CD4) vs. 0.881 (SCMM-CD8) vs. 0.961 (PCT + SCMM-CD4) vs. 0.915 (PCT+SCMM-CD8), P < 0.001]. Conclusion: SCMM-CD4 was shown to be a better diagnostic biomarker of early sepsis when compared with the traditional biomarker, PCT. Furthermore, the value of the combination of PCT and SCMM-CD4 in the diagnosis of early sepsis was better than that of SCMM-CD4 alone.

Sirolimus treatment for tuberous sclerosis complex prior to epilepsy: Evidence from a registry-based real-world study.

OBJECTIVE: To evaluate whether sirolimus treatment could relieve the later burden of new-onset seizures in patients with tuberous sclerosis complex (TSC) prior to epilepsy. METHODS: A real-world matched case-control study was nested in another registry cohort study. Infants with TSC (<12 months old) without seizures whose parents agreed on sirolimus treatment for other symptoms were eligible for inclusion to the early sirolimus (ES) group. These patients were enrolled from 2015 to 2018. Controls in the late sirolimus (LS) group were matched from the registry cohort database for 2015-2018. Age and genotype were used as the initial stratifying criteria and other symptoms as the greedy matching criteria at a matching ratio of 1:4. None of the preventive drugs were introduced before seizure onset or before 2 years of age in the LS group. Both groups were followed up until June 2020. The primary objective was a comparison of the characteristics of the first seizure between the two groups. The secondary objective was the assessment of the final seizure status at the endpoint. RESULTS: There were 42 and 168 patients with TSC in the ES and LS groups, respectively. Early sirolimus treatment significantly reduced the seizure onset, especially in the patients aged <6 months. The mean onset-age was significantly delayed by sirolimus treatment (11.34±7.93 months vs. 6.94±6.03 months, P<0.001). The subtype of seizures that benefited the most was spastic (onset) seizures (all were infantile spasms) [5/42 (11.90%) vs. 73/168 (43.45%), P<0.001]; these seizures were either eliminated or alleviated. The sirolimus treatment addition prior to seizures was more effective than its addition after seizures in reducing drug-resistant epilepsy [10/42 (23.81%) vs. 70/147 (47.62%), P=0.004]. CONCLUSION: Early sirolimus treatment for TSC effectively modified the disease by preventing infantile spasms, delaying seizure onset, and relieving its severity. The anti-epileptogenic effect of sirolimus may be time- and dose-dependent.

A Retrospective Study of Recurrent Bacterial Meningitis in Children: Etiology, Clinical Course, and Treatment.

Objectives: Recurrent bacterial meningitis (RBM) is a rare but life-threatening disease. This study aims to analyze the clinical features, potential causes, and therapeutic outcomes of RBM in children. Methods: This article retrospectively reviews the clinical characteristics, etiologies, and treatments in children with RBM hospitalized in Hebei children's hospital from 2012 to 2020. Results: A total of 10 children with RBM, five males and five females, were included in this study. The age of RBM in children spans from the neonatal stage to the childhood stage. The underlying illnesses were identified and classified as cerebrospinal fluid rhinorrhea (1 case), humoral immunodeficiency with Mondini dysplasia (1 case), common cavity deformity with cerebrospinal fluid ear leakage (1 case), Mondini malformations (2 cases), incomplete cochlear separation type I with a vestibular enlargement (2 cases), local inflammation of the sphenoid bone caused by cellulitis (1 case), congenital skull base defects (1 case), and congenital dermal sinus with intraspinal abscess (1 case). 6 patients chose targeted therapy for potential reasons. Conclusions: Congenital abnormalities or acquired injuries lead to intracranial communication with the outside world, which can quickly become a portal for bacterial invasion of the central nervous system, resulting in repeated infections.

Patient and Clinical Factors at Admission Affect the Levels of Neutralizing Antibodies Six Months after Recovering from COVID-19.

The rate of decline in the levels of neutralizing antibodies (NAbs) greatly varies among patients who recover from Coronavirus disease 2019 (COVID-19). However, little is known about factors associated with this phenomenon. The objective of this study is to investigate early factors at admission that can influence long-term NAb levels in patients who recovered from COVID-19. A total of 306 individuals who recovered from COVID-19 at the Tongji Hospital, Wuhan, China, were included in this study. The patients were classified into two groups with high (NAbhigh, n = 153) and low (NAblow, n = 153) levels of NAb, respectively based on the median NAb levels six months after discharge. The majority (300/306, 98.0%) of the COVID-19 convalescents had detected NAbs. The median NAb concentration was 63.1 (34.7, 108.9) AU/mL. Compared with the NAblow group, a larger proportion of the NAbhigh group received corticosteroids (38.8% vs. 22.4%, p = 0.002) and IVIG therapy (26.5% vs. 16.3%, p = 0.033), and presented with diabetes comorbidity (25.2% vs. 12.2%, p = 0.004); high blood urea (median (IQR): 4.8 (3.7, 6.1) vs. 3.9 (3.5, 5.4) mmol/L; p = 0.017); CRP (31.6 (4.0, 93.7) vs. 16.3 (2.7, 51.4) mg/L; p = 0.027); PCT (0.08 (0.05, 0.17) vs. 0.05 (0.03, 0.09) ng/mL; p = 0.001); SF (838.5 (378.2, 1533.4) vs. 478.5 (222.0, 1133.4) µg/L; p = 0.035); and fibrinogen (5.1 (3.8, 6.4) vs. 4.5 (3.5, 5.7) g/L; p = 0.014) levels, but low SpO2 levels (96.0 (92.0, 98.0) vs. 97.0 (94.0, 98.0)%; p = 0.009). The predictive model based on Gaussian mixture models, displayed an average accuracy of 0.7117 in one of the 8191 formulas, and ROC analysis showed an AUC value of 0.715 (0.657-0.772), and specificity and sensitivity were 72.5% and 67.3%, respectively. In conclusion, we found that several factors at admission can contribute to the high level of NAbs in patients after discharge, and constructed a predictive model for long-term NAb levels, which can provide guidance for clinical treatment and monitoring.

Colloidal gold immunochromatographic assay (GICA) is an effective screening method for identifying detectable anti-SARS-CoV-2 neutralizing antibodies.

INTRODUCTION: A large number of COVID-19 patients are in recovery, and millions of people are vaccinated for COVID-19 globally. This calls for a rapid screening strategy of SARS-CoV-2 protective antibodies, generated in rehabilitated and vaccinated populations. METHODS: Serum samples collected over a follow-up period of six months from 306 COVID-19 cases discharged from Wuhan Tongji Hospital were analyzed. Anti-S Abs were detected by colloidal gold immunochromatographic assay (GICA), and neutralizing antibodies (nAbs) were detected by chemiluminescent microparticle immunoassay (CMIA). RESULTS: Most COVID-19 survivors tested positive for anti-S Abs (83.7%) and nAbs (98.0%) 6 months after being discharged from the hospital, and the levels of anti-S Abs in the blood were highly positively correlated with nAbs (r = 0.652, P < 0.0001). The positivity rate of nAbs for patients with anti-S Abs positive was 100%. CONCLUSIONS: There is a good agreement between anti-S Abs detected by GICA and nAbs detected by CMIA. It indicates that anti-S Abs detected by GICA may be used as a cheaper screening strategy for detectable SARS-CoV-2 nAbs in COVID-19 convalescent individuals.

Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia-reperfusion injury via upregulation of splenic regulatory T cells.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25+Foxp3+ regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor ß1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen.

Sirolimus Can Increase the Disappearance Rate of Cardiac Rhabdomyomas Associated with Tuberous Sclerosis: A Prospective Cohort and Self-Controlled Case Series Study.

OBJECTIVES: To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. STUDY DESIGN: The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. RESULTS: A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. CONCLUSIONS: Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.

Prevalence of Dysphagia in China: An Epidemiological Survey of 5943 Participants.

OBJECTIVE: To determine the prevalence of dysphagia among an older population and patients with stroke, head and neck cancers (HNCs) or neurodegenerative diseases (NDDs) in China, to identify the factors associated with this condition, and to explore the relationship between dysphagia and nutritional status. METHODS: This study included participants 65 years and older living in the community or in nursing homes and patients who had sustained a stroke, HNC, or NDD also recruited in hospitals from 14 provinces of China. The presence of dysphagia was determined by use of a questionnaire, water swallowing test, and/or a videofluoroscopic swallowing study. Logistic regression analysis was used to assess the possible associated risk factors. Body mass index was assessed as an indicator of malnutrition. RESULTS: A total of 5943 persons met the inclusion criteria and 2341 (39.4%) were identified with dysphagia, including the following: 51.14% of patients with stroke, 34.4% in HNCs, 48.3% in NDDs, and 19.2% of otherwise healthy older adults. The elderly with comorbidity (OR = 2.90, p < 0.01) and stroke patients (OR = 2.27, p < 0.01) were significantly more likely to exhibit signs of dysphagia. Dysphagic participants were at significantly greater risk of malnutrition (OR = 1.91, p < 0.01) compared to those without dysphagia. CONCLUSION: Dysphagia is prevalent in China among older individuals and people who have suffered a stroke, HNCs, or NDDs. The prevalence of dysphagia increases steadily with increasing age and presence of comorbid disease. People with dysphagia are more likely to suffer from malnutrition.

A Retrospective Analysis Of Different Contingent Screening Models For Fetal Down Syndrome In Southwestern China.

To discuss combinations of traditional screening and noninvasive prenatal screening (NIPS) and to compare which traditional screening is the most suitable first-line screening approach to NIPS, pregnant women were recruited in this retrospective observational study. Pregnant women underwent one of four traditional screening tests. The 9 contingent models were combined by high risk cut-offs of 1:50, 1:100, 1:270 and intermediate risk cut-offs of 1:1000, 1:1500, 1:2000. We analyzed cost and performance of various screening models with contingent screening of different risk cut-offs. Compared with other screening tests, combined first-trimester screening (CFTS) had the lowest proportion of high risk (≥1:270) with the highest detection rate (DR) (78.79%) and the lowest proportion of intermediate risk (1:271~1:1000). When intermediate risk was 1:51 ~1:1500, CFTS as first-line screening had the lowest cost with DR of 93.94%. Other screening tests as the first-line screening with intermediate risk of 1:51~1:1000 had the lowest cost, there DR were 90.91%, 84.62%, 91.67%, respectively. Our study demonstrated if only one traditional screening was allowed to screen pregnant women, CFTS was recommended as the first choice. According to local health and economic conditions, adopting appropriate traditional screening with suitable cut-offs as first-line screening will contributed to a cost-effective screening model.

[Analysis of 21 723 Pregnant Women's First Trimester Screening for Down Syndrome in Sichuan Province].

OBJECTIVE: To compare the effect of different first-trimester screening programmes for Down syndrome in Sichuan Province. METHODS: We retrospectively collected the data of singleton pregnancies that were screened by serum biochemistry markers combined with nuchal translucency screening tests in the first trimester in Prenatal Diagnosis Center of West China Second University Hospital of Sichuan University from January 2011 to December 2017. The fetal chromosome results were obtained by amniocentesis or by telephone follow-up. The screening effect of maternal age, nuchal translucency thickness, maternal serum biochemistry markers and combined screening in the first trimester were analyzed. RESULTS: Among the 21 723 singleton pregnancies, 33 cases were diagnosed as Down syndrome, and 19 cases were diagnosed as trisomy 18 sex chromosome abnormalities were found in 4 cases, and other chromosome abnormalities were found in 8 cases. For the combined screening, the detection rate of Down syndrome was 72.73%, and the false positive rate was 2.49%; the detection rate of trisomy 18 syndrome was 73.68% with the false positive rate of 0.39%. With a 5% false positive rate, maternal age, nuchal translucency thickness, serum biochemistry markers and combined screening would respectively detect 15.15%, 57.58%, 60.61% and 87.88% of Down syndrome fetuses. CONCLUSION: Compared with the other three screening programmes, the combined screening can effectively screen fetuses with Down syndrome and other chromosomal abnormalities.

Application Effects of Whole Course High-Quality Nursing on Patients with Liver Cancer during Radiotherapy.

BACKGROUND: To explore the application effects of whole course high-quality nursing on patients with liver cancer during radiotherapy. METHODS: One hundred and five patients with liver cancer who received radiotherapy in Liaocheng People's Hospital, Liaocheng, China from March 2010 to February 2012 were selected and divided into a control group (42 cases with routine nursing) and an experimental group (63 cases with whole course high-quality nursing). The two groups of patients were observed and compared in terms of clinical data and the Activity of Daily Living (ADL) score before and after nursing (1 course of treatment/6 week). The Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to evaluate and compare the patients' anxiety and depression before and after nursing. Adverse reactions during radiotherapy and nursing satisfactory of patients were observed and compared between the two groups. RESULTS: After nursing, the ADL score and the nursing satisfaction in the experimental group was significantly higher than that in the control group (P<0.05). The SDS and SAS scores in the 2 groups before nursing were significantly higher than those after nursing (P<0.05). The total incidence of adverse reactions in the control group was significantly higher than that in the experimental group (P<0.05). CONCLUSION: Whole course high-quality nursing can improve the negative emotions, quality of life and nursing satisfaction, and reduce adverse reactions of patients with liver cancer during radiotherapy.

Gender-specific associations between activities of daily living disability and depressive symptoms among older adults in China: Evidence from the China Health and Retirement Longitudinal Study.

PURPOSE: To evaluate the associations between BADL/IADL disability and depressive symptoms from the perspective of gender among older adults in China. METHODS: This cross-sectional study used the data from the second wave of the China Health and Retirement Longitudinal Study (CHARLS). The sample included 3463 older adults aged 60 years and older across China. Multivariable logistic regression models were conducted. RESULTS: Among 3463 older adults, 1240 (35.8%) were classified as depressed, the prevalence of BADL and IADL disabilities were 756 (21.8%) and 1194 (34.5%), respectively. After controlling for covariates, BADL/IADL disability was significantly associated with an increased risk of depression prevalence both in men and women among older adults. Compared with IADL independent, IADL disability was about two times more likely to develop depressive symptoms in men (OR = 2.165, 95% CI = 1.661-2.822), which was much higher than that in women (OR = 1.748, 95% CI = 1.415-2.160). In contrast, the odds of being depressed for women with BADL disability (OR = 1.824, 95% CI = 1.447-2.299) were much higher than the odds for men with BADL disability (OR = 1.791, 95% CI = 1.348-2.379). CONCLUSIONS: Older adults with BADL/IADL disability were more likely to have depressive symptoms both for men and women. However, the associations between depressive symptoms and BADL/IADL disability were different in gender. Our results suggest that differential institutional care service and appropriate strategies for improvement in mental health are required.

Prospective molecular mechanism of COL5A1 in breast cancer based on a microarray, RNA sequencing and immunohistochemistry.

Breast cancer (BC) has a complex etiology and pathogenesis, and is the most common malignant tumor type in females, in USA in 2018, yet its relevant molecular mechanisms remain largely unknown. The collagen type V α­1 chain (COL5A1) gene is differentially expressed in renal and ovarian cancer. Using bioinformatics methods, COL5A1 was determined to also be a significant gene in BC, but its association with BC has not been sufficiently reported. COL5A1 microarray and relevant clinical data were collected from the Gene Expression Omnibus, The Cancer Genome Atlas and other databases to summarize COL5A1 expression in BC and its subtypes at the mRNA and protein levels. All associated information was comprehensively analyzed by various software. The clinical significance of the mutation was obtained via the cBioPortal. Furthermore, Gene Ontology functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were also performed to investigate the mechanism of COL5A1 in BC. Immunohistochemistry was also conducted to detect and confirm COL5A1 expression. It was determined that COL5A1 was highly expressed in BC tissues, compared with normal tissues at the mRNA level [standard mean difference, 0.84; 95% confidence interval (CI), 0.60­1.07; P=0.108]. The area under the summary receiver operator characteristic curve for COL5A1 was 0.87 (95% CI, 0.84­0.90). COL5A1 expression was altered in 32/817 (4%) sequenced samples. KEGG analysis confirmed the most notable pathways, including focal adhesion, extracellular matrix­receptor interaction and regulation of the actin cytoskeleton. Immunohistochemical detection was used to verify the expression of COL5A1 in 136 selected cases of invasive BC tissues and 55 cases of adjacent normal tissues, while the rate of high expression of COL5A1 in BC was up to 90.4%. These results indicated that COL5A1 is highly expressed at the mRNA and protein levels in BC, and the prognosis of patients with BC with high COL5A1 expression may be reduced; therefore, COL5A1 may be used independently or combined with other detection factors in BC diagnosis.

Effects of Aluminum Hydroxide and Layered Double Hydroxide on Asphalt Fire Resistance.

When a fire occurs in a tunnel, the instantaneous high temperature and smoke cause great danger to people. Therefore, the asphalt pavement material in the tunnel must have sufficient fire resistance. In this study, the effects of aluminum hydroxide and layered double hydroxide on the fire resistance of styrene-butadiene-styrene (SBS) polymer-modified asphalt was investigated. The fire resistance of the asphalt was evaluated by using a limiting oxygen index (LOI). The impact of aluminum hydroxide (ATH), layered double hydroxide (LDHs), and mixed flame retardant (MFR) on LOI was studied. The synergistic fire resistance mechanism of ATH and LDHs in asphalt binder was analyzed by using an integrated thermal analyzer‒mass spectrometry combined system (TG-DSC-MS) and Fourier transform infrared spectrometer (FTIR). The experimental results indicated that the main active temperature range of these flame retardants was 221⁻483 °C. The main components of smoke were methane, hydroxyl, water, carbon monoxide, aldehyde, carbon dioxide, etc. The addition of flame retardants could inhibit the production of methane, carbon monoxide, and aldehyde. Moreover, due to the good synergistic effects of ATH and LDHs, 20 wt % MFR had the best fire resistance.

Calcification in cerebral parenchyma affects pharmacoresistant epilepsy in tuberous sclerosis.

PURPOSE: Tuberous sclerosis (TSC) is an autosomal dominant inherited disease caused by mutations in the TSC1 or TSC2 gene and results in the over-activation of the mammalian target of the rapamycin (mTOR) signaling pathway. Rapamycin, an mTOR inhibitor, is clinically used to treat hamartomatous lesionsas in TSC and its effect on controlling epilepsy is also reported in many studies. This study aims to evaluate the risk factors of pharmacoresistant epilepsy in patients with TSC receiving long-term rapamycin treatment. METHOD: A total of 108 patients with TSC taking rapamycin for over 1 year were enrolled in this study. Factors that might influence seizure control were statistically analyzed by multiple factor analysis. A subgroup analysis was also conducted to access the relationship between calcified epileptic foci and pharmacoresistant epilepsy. (Clinical trial registration number: ChiCTR-OOB-15006535(2015-05-29)). RESULTS: Seizure was controlled in 53 patients but was not managed in 55 patients considered to be drug resistant. Logistic regression analysis showed that calcification in the cerebral parenchyma was a risk factor of pharmacoresistant epilepsy [P = 0.006, odds ratio (OR) = 4.831 (1.577, 14.795)]. Fifteen of 17 patients with calcified epileptic foci suffered from pharmacoresistant epilepsy (88.2%). Seizures in patients with calcified epileptic foci were probably pharmacoresistant (P = 0.010). CONCLUSION: Calcification in epileptic foci strongly indicates pharmacoresistant epilepsy in patients with TSC even when treated with appropriate anti-epilepsy drugs (AEDs) and rapamycin. Calcification can be used to evaluate pharmacoresistant epilepsy in patients with TSC.