Factors predicting depressive symptoms in parents of children with autism spectrum disorder in eastern China.

BACKGROUND: Parents of children with autism spectrum disorder (ASD) are at a higher risk of depression than parents of typically developing children and those of children with other developmental disorders. Depression affects the well-being and quality of life of parents of children with ASD and has serious consequences for the long-term health outcomes of children with ASD. Therefore, this study explored the current status of depressive symptoms in parents of children with ASD in eastern China and further analyzed multiple aspects of the predictors of depressive symptoms. METHODS: A multicenter cross-sectional survey was conducted among parents of children with ASD in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China. A structured questionnaire that focused on child-related factors, parent-related factors, depressive symptoms, courtesy stigma, and social support was used to obtain data. Binary logistic regression was used to identify the independent predictors of depressive symptoms in parents of children with ASD. RESULTS: A total of 409 parents of children with ASD were recruited, of whom 18.8% had depressive symptoms. Parents of children with ASD who raised a child who spoke few to no words (odds ratio [OR]: 2.747, 95% confidence interval [CI]: 1.026-7.357), claimed a high economic burden (OR: 3.215, 95% CI: 1.234-8.379), reported no change or increased severity of ASD in their children (OR: 2.518, 95% CI: 1.108-5.720), and those with a higher courtesy stigma score (OR: 1.189, 95% CI: 1.093-1.294) were more likely to have depressive symptoms. Conversely, parents of children with ASD who were employed (OR: 0.427, 95% CI: 0.201-0.907), satisfied with their current marital status (OR: 0.429, 95% CI: 0.221-0.834), and those with a higher social support score (OR: 0.973, 95% CI: 0.950-0.996) were less likely to have depressive symptoms. CONCLUSIONS: Depressive symptoms are common in parents of children with ASD in eastern China. Therefore, screening and intervention for depressive symptoms in parents of children with ASD is necessary, especially for those with high-risk factors.

Fear of childbirth and its determinants in pregnant women in the third trimester: a cross-sectional study.

BACKGROUND: Fear of childbirth (FOC) is a prevalent issue among pregnant women and significantly relates to adverse outcomes for the mother and child. However, it is not clear the prevalence and risk factors of FOC among pregnant women in a region with a moderate level of economic development in China. The aim of this study was to investigate the prevalence and risk factors of FOC among pregnant women in the third trimester of pregnancy in Lianyungang city, Eastern China. METHODS: A cross-sectional survey was conducted from December 2022 to February 2023 among pregnant women in the third trimester who met the inclusion criteria and visited Lianyungang Maternal and Child Health Hospital in Jiangsu Province, Eastern China. A structured questionnaire including sociodemographic characteristics, clinical characteristics, FOC, family function, doctor-patient communication, social support, general self-efficacy, anxiety, depression, insomnia symptoms, and quality of life was used to collect data. A multiple linear regression model was used to identify predictors of FOC. RESULTS: This study included 535 pregnant women in the third trimester. The mean score of FOC was 30.67 ± 10.18, and the median score was 29.00. The prevalence of FOC was 56.64%. Multiple linear regression analysis revealed that pregnant women with electronic screen exposure time more than 5 h per day (ß = 2.02, 95%CI: 0.50-3.53, P < 0.05), no history of cesarean section (ß = 2.66, 95%CI: 0.61-4.71, P < 0.05), likes sour food or hates greasy food (ß = 1.75, 95%CI: 0.00-3.50, P < 0.05), anxiety (ß = 0.50, 95%CI: 0.21-0.80, P < 0.05) and depression (ß = 0.30, 95%CI: 0.04-0.57, P < 0.05) were more likely to have a greater level of FOC than their counterparts. However, a significantly lower level of FOC was observed in pregnant women who were multipara (ß=-1.64, 95%CI: -3.27-0.01, P < 0.05), not worrying about delivery without family members (ß=-3.75, 95%CI: -5.26-2.25, P < 0.001), had good family function (ß=-0.32, 95%CI: -0.64-0.00, P < 0.05) and doctor-patient communication (ß=-0.33, 95%CI: -0.64-0.02, P < 0.05). CONCLUSIONS: The prevalence of FOC was high in Lianyungang city, Eastern China. FOC is influenced by multiple factors. There is an urgent need to develop interventions to reduce the prevalence of FOC in the third trimester of pregnancy, and to pay attention to pregnant women with risk factors for FOC.

Prevalence and associated factors of insomnia symptoms among pregnant women in the third trimester in a moderately developing region of China.

BACKGROUND: Insomnia is the most common sleep disorder in the general population, especially among pregnant women, and it is considered a major public health issue. Not only can it cause mental and physical problems in pregnant women, but it may also affect the growth of the fetus. However, there are few reports on the prevalence and influencing factors of insomnia symptoms in third-trimester women in China. The objective of this study was to assess the prevalence of insomnia symptoms among pregnant women in the third trimester in a moderately developing region of China and to further explore the associated factors of insomnia symptoms from various aspects. METHODS: A cross-sectional survey was conducted among eligible pregnant women in the third trimester from December 2022 to February 2023. Data on socio-demographic characteristics, clinical characteristics, and behavioral and psychological characteristics of pregnant women were collected through a structured questionnaire. The Chi-square test and multivariate logistics regression were applied to explore the associated factors of insomnia symptoms. RESULTS: A total of 535 pregnant women in the third trimester were included in this study, and the prevalence of insomnia symptoms was 59.8%. Multivariate logistic regression analysis revealed that pregnant women who lived together with elders (OR: 0.58, 95% CI: 0.40-0.86), had low perceived stress (OR: 0.58, 95% CI: 0.35-0.97), had no threatened abortion (OR: 0.55, 95% CI: 0.32-0.93) and had good doctor-patient communication (OR: 0.66, 95% CI: 0.45-0.98) were more likely to stay away from insomnia symptoms. However, pregnant women with anxiety symptoms (OR: 2.27, 95% CI: 1.28-4.03), fear of childbirth (OR: 1.63, 95% CI: 1.11-2.40) and a high experience of COVID-19 fear (OR: 1.61, 95% CI: 1.03-2.54) tended to have insomnia symptoms. CONCLUSIONS: The prevalence of insomnia symptoms in pregnant women is high in Lianyungang city in eastern China in the third trimester. Insomnia symptoms is influenced by multiple factors. There is an urgent need to develop interventions to reduce the prevalence of insomnia symptoms in the third trimester and to focus on pregnant women with risk factors for insomnia symptoms.

[Analysis of genetic variants in a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism without seizures].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial malformations without epilepsy (IDDBCS). METHODS: A child who had visited the Lianyungang Maternal and Child Health Care Hospital in April 2021 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of his family members. RESULTS: The child, a 3-year-and-4-month-old male, had presented with global developmental delay and cranial malformation. Genetic testing revealed that he has harbored a heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene, for which both of his parents were of the wild type. This low-frequency variant may alter the structure and function of the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting). CONCLUSION: The heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene probably underlay the IDDBCS in this patient.

Preferential Localization of MUC1 Glycoprotein in Exosomes Secreted by Non-Small Cell Lung Carcinoma Cells.

Lung cancer remains to be the leading cause of cancer-related mortality worldwide. Finding new noninvasive biomarkers for lung cancer is still a significant clinical challenge. Exosomes are membrane-bound, nano-sized vesicles that are released by various living cells. Studies on exosomal proteomics may provide clues for developing clinical assays. In this study, we performed semi-quantitative proteomic analysis of proteins that were purified from exosomes of NCI-H838 non-small cell lung cancer cell line, with total cellular membrane proteins as control. In the exosomes, LC-MS/MS by data-independent analysis mode identified 3235 proteins. THBS1, ANXA6, HIST1H4A, COL18A1, MDK, SRGN, ENO1, TUBA4A, SLC3A2, GPI, MIF, MUC1, TALDO1, SLC7A5, ICAM1, HSP90AA1, G6PD, and LRP1 were found to be expressed in exosomes at more than 5-fold higher level as compared to total cellular membrane proteins. A well-known cancer biomarker, MUC1, is expressed at 8.98-fold higher in exosomes than total cellular membrane proteins. Subsequent analysis of plasma exosomes from non-small cell lung cancer (NSCLC) patients by a commercial electrochemiluminescence immunoassay showed that exosomal MUC1 level is 1.5-fold higher than healthy individuals (mean value 1.55 ± 0.16 versus mean value 1.05 ± 0.06, p = 0.0213). In contrast, no significant difference of MUC1 level was found between NSCLC patients and healthy individuals' plasma (mean value 5.48 ± 0.65 versus mean value 4.16 ± 0.49). These results suggest that certain proteins, such as MUC1, are selectively enriched in the exosome compartment. The mechanisms for their preferential localization and their biological roles remain to be studied.

[Effects of Maxing Shigan Decoction Decocted by Different Methods and Its Drug Containing Serum on Neuraminidase Activity of Influenza A Virus].

Objective To observe the effects of Maxing Shigan Decoction (MSD) decocted by different methods and its drug containing serum on neuraminidase ( NA ) activity of influenza A virus (IAV). Methods The effects of MSD decocted by different methods, its corresponding drug containing serums , and drug containing serum in inhibiting the proliferation of virus on NA activity of IAV were detected using 2-(4-methyl umbelliferyl )-α-D-N-acetyl neuraminic acid (MUNANA) as substrate. Results (1) Effect of MSD on NA activity of IAV: OD value was less in groups with Ephedra decocted 25-min earlier and 30-min earlier than the group with four drugs decocted at the same time (P <0. 05, P <0. 01) ; (2) Effect of MSD on NA activity of IAV: OD value was less in groups with Ephedra decocted 30-min earlier and 40-min earlier than the group with four drugs decocted at the same time (P <0. 05, P <0. 01) ; (3) In the process of inhibiting viral multiplication, effect of MSD containing serum on NA activity of IAV: OD value was less in groups with Ephedra decocted 5 -20 min earlier, 30 min earlier, 35 min earlier than the group with four drugs decocted at the same time (P <0. 05, P <0. 01). In terms of drug concentration, OA value decreased more in 6. 25% and 12. 50% MSD containing serums than in 25. 00% MSD containing serum (P <0. 01). Conclusion MSD decocted by different methods might lead to different anti-IAV effects.

Novel KMT5B variant associated with neurodevelopmental disorder in a Chinese family: A case report.

Background: We report here the clinical and genetic features of KMT5B-related neurodevelopmental disorder caused by a novel heterozygous frameshift variant in KMT5B in a Chinese family. Case presentation: A 7-year-old Chinese boy with mild-to-moderate intellectual disability, significant language impairment, motor disability, and coordination difficulties presented to our hospital because he "could not speak and did not look at others." He was diagnosed with autism spectrum disorder previously owing to developmental delays in cognition, language expression, and understanding. The child also had variable nonspecific features including macrocephaly, wide button-hole space and nasal bridge, low ear, social behavior disorder, and foot deformities. Exome sequencing (ES) revealed that both the proband and his younger brother had inherited a novel heterozygous frameshift variant c.438_439ins[ASD; KT192064.1:1_310] of the KMT5B gene from their father. Bioinformatics analysis showed that the novel mutation affected the structure of the KMT5B pre-SET domain, mainly in the α-helix region. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this type of variant was eventually determined to be likely pathogenic (PVS1+PM2_P). Conclusions: Our investigation expands the mutation spectrum of KMT5B to help us to better understand KMT5B-related neurodevelopmental disorder.

The role of self-esteem as moderator of the relationship between experienced stigma and anxiety and depression among tuberculosis patients.

Anxiety and depression are very common in tuberculosis (TB) patients and can adversely affect TB treatment adherence, ultimately leading to higher morbidity, mortality and drug resistance. Therefore, the aim of this study was to identify the association among experienced stigma, self-esteem and anxiety and depression, and to further explore whether self-esteem could be a moderator in the association between experienced stigma and anxiety and depression in TB patients. A total of 473 TB patients from Dalian, Liaoning Province, Northeast China participated in a cross-sectional survey. A structured questionnaire was developed to collect data. Hierarchical multiple regression was used to analyze the association among experienced stigma, self-esteem and experienced stigma × self-esteem interaction with anxiety and depression. Simple slope analysis was applied to visualize the interaction. Experienced stigma was positively associated with anxiety (B = 0.307, P < 0.01) and depression (B = 0.277, P < 0.01), and self-esteem was negatively associated with anxiety (B = - 0.215, P < 0.01) and depression (B = - 0.351, P < 0.01) in TB patients. The association between experienced stigma and anxiety was different in the low (1 standard deviation (SD) below the mean, B = 0.376, standard error (SE) = 0.056, P < 0.01) and high (1 SD above the mean, B = 0.228, SE = 0.060, P < 0.01) groups of self-esteem. Additionally, the association between experienced stigma and depression was also different in the low (1 SD below the mean, B = 0.363, SE = 0.053, P < 0.01) and high (1 SD above the mean, B = 0.179, SE = 0.056, P < 0.01) groups of self-esteem. Self-esteem could moderate the association between experienced stigma and anxiety and depression. In addition to reducing experienced stigma, enhancing self-esteem as a way to reduce the impact of experienced stigma on anxiety and depression can also help improve the mental health of TB patients.

Blood nesfatin-1 levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

Background: Previous studies have investigated the relationship between nesfatin-1 level and polycystic ovary syndrome (PCOS). However, these studies have produced conflicting results. Thus, in this meta-analysis, we aimed to clarify the association between blood nesfatin-1 levels and PCOS, and the ability of nesfatin-1 as a biomarker in PCOS. Methods: Meta-analysis was performed using STATA 12.0 software. We computed standard mean difference (SMD) and 95% confidence interval (CI) regarding the comparison of blood nesfatin-1 in patients with PCOS and controls. Results: The present meta-analysis showed no significant difference in blood nesfatin-1 level between patients with PCOS and controls with a random effects model (SMD = 0.03; 95%CI: -0.71, 0.77; I2 = 97.1%, p value for Q test < 0.001). Subgroup analysis for different ethnicities reported no significant difference in blood nesfatin-1 level between patients with PCOS and controls in both Caucasian and Asian populations. Subgroup analysis for different sample types reported no significant difference in serum nesfatin-1 level between patients with PCOS and controls. Subgroup studies reported no significant difference in blood nesfatin-1 level between PCOS and controls in both obese and non-obese populations. Conclusion: In conclusion, there is no significant relationship between blood nesfatin-1 levels and PCOS.

Effect of biological, psychological, and social factors on maternal depressive symptoms in late pregnancy: a cross-sectional study.

Introduction: Depression commonly occurs during pregnancy and has become a major public health concern. Depression not only affects the individual but also causes adverse consequences for families and children. However, little is known regarding the depression status and its influencing factors in women during late pregnancy in China. This study aimed to assess the prevalence of maternal depressive symptoms in late pregnancy during the coronavirus disease 2019 (COVID-19) pandemic and further explore the effect of biological, psychological, and social factors on depressive symptoms. Methods: An institution-based cross-sectional survey was conducted among eligible women in the late pregnancy stage and underwent prenatal examination at Lianyungang Maternal and Child Health Hospital in Jiangsu Province, Eastern China from December 2022 to February 2023. Data regarding depressive symptoms and biological, psychological, and social factors of the pregnant women were collected via a structured questionnaire. Chi-square test, Fisher's exact tests, and binary logistics regression were used to analyze the data. Results: In total, 535 women in the late pregnancy stage were included in this study, 75 (14.0%) of whom exhibited depressive symptoms. A binary logistic regression analysis revealed that pregnant women who were multiparous (OR: 2.420, 95% CI: 1.188-4.932) and had moderate or severe insomnia symptoms (OR: 4.641, 95% CI: 1.787-12.057), anxiety (OR: 8.879, 95% CI: 4.387-17.971), high fear of COVID-19 (OR: 2.555, 95% CI: 1.255-5.199), moderate or severe family dysfunction (OR: 2.256, 95% CI: 1.141-4.461), and poor social support (OR: 2.580, 95% CI: 1.050-6.337) tended to show depressive symptoms. Conversely, pregnant women who received regular prenatal care (OR: 0.481, 95% CI: 0.243-0.951) and had good drinking water quality at home (OR: 0.493, 95% CI: 0.247-0.984) were more likely to avoid developing depressive symptoms. Conclusion: This study found that the prevalence of maternal depressive symptoms during late pregnancy was high and had multiple influencing factors. Thus, screening for depressive symptoms in women in the late pregnancy stage and providing special intervention programs are necessary, especially for those with risk factors.

Courtesy stigma among primary caregivers of children with autism spectrum disorder in eastern China.

Introduction: The experience and perception of stigma is a common problem among primary caregivers of children with autism spectrum disorder (ASD), and has a profound adverse impact on primary caregivers and children with ASD; however, few studies have explored courtesy stigma among primary caregivers of children with ASD in the Chinese context. The aim of this study was to explore the status of courtesy stigma among primary caregivers of children with ASD in Lianyungang, Jiangsu Province, Eastern China, and to conduct in-depth analysis of its predictors from multiple perspectives. Methods: An institution-based multi-center cross-sectional survey was conducted in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China, from October 2022 to February 2023. A structured questionnaire to assess child-related factors, primary caregiver-related factors, courtesy stigma, general self-efficacy, and social support, was used to collect data. Predictors of courtesy stigma among primary caregivers of children with ASD were identified by linear regression. Results: A total of 428 primary caregivers of children with ASD were recruited. The mean ± standard deviation (SD) score for courtesy stigma was 7.49 ± 4.13. Multiple linear regression analysis revealed that primary caregivers of children with ASD who were not too satisfied with their current marital status (ß = 1.21, 95% CI: 0.34-2.08, p < 0.05) were more likely to have a high courtesy stigma; however, significantly lower courtesy stigma was observed in primary caregivers of children with ASD who were not picky eaters (ß = -1.33, 95% CI: -2.08 - -0.58, p < 0.05), and who reported low level challenge in caring for children with ASD (ß = -1.16, 95% CI: -2.20 - -0.12, p < 0.05), good general self-efficacy (ß = -0.16, 95% CI: -0.25 - -0.06, p < 0.05), and good social support (ß = -0.04, 95% CI: -0.08 - -0.01, p < 0.05). Conclusion: There is a high level of courtesy stigma among primary caregivers of children with ASD in eastern China, and it is affected by numerous factors. More resources should be directed to groups that are more likely to experience stigma.

Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Background: Hypertensive cerebral small vessel disease (HT-CSVD) is a cerebrovascular clinical, imaging and pathological syndrome caused by hypertension (HT). The condition manifests with lesions in various vessels including intracranial small/arterioles, capillaries, and small/venules. Hypertensive cerebral small vessel disease has complex and diverse clinical manifestations. For instance, it can present as an acute stroke which progresses to cause cognitive decline, affective disorder, unstable gait, dysphagia, or abnormal urination. Moreover, hypertensive cerebral small vessel disease causes 25-30% of all cases of ischemic strokes and more than 50% of all cases of single or mixed dementias. The 1-year recurrence rate of stroke in cerebral small vessel disease patients with hypertension is 14%. In the early stage of development, the symptoms of hypertensive cerebral small vessel disease are concealed and often ignored by patients and even clinicians. Patients with an advanced hypertensive cerebral small vessel disease manifest with severe physical and mental dysfunction. Therefore, this condition has a substantial economic burden on affected families and society. Naotaifang (NTF) is potentially effective in improving microcirculation and neurofunction in patients with ischemic stroke. In this regard, this multicenter randomized controlled trial (RCT) aims to furtherly evaluate the efficacy and safety of naotaifang capsules on hypertensive cerebral small vessel disease. Methods: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 388 eligible subjects were recruited from the First Hospital of Hunan University of Chinese Medicine, Hunan Academy of Chinese Medicine Affiliated Hospital, the First Hospital of Shaoyang University, the First Traditional Chinese Medicine Hospital of Changde, and Jiangmen Wuyi Hospital of Traditional Chinese Medicine from July 2020 to April 2022. After a 4-week run-in period, all participants were divided into the intervention group (represented by Y-T, N-T) and control group (represented by Y-C, N-C); using a stratified block randomized method based on the presence or absence of brain damage symptoms in hypertensive cerebral small vessel disease (represented by Y and N). The Y-T and N-T groups were administered different doses of naotaifang capsules, whereas Y-C and N-C groups received placebo treatment. These four groups received the treatments for 6 months. The primary outcome included Fazekas scores and dilated Virchow-robin spaces (dVRS) grades on magnetic resonance imaging (MRI). The secondary outcomes included the number of lacunar infarctions (LI) and cerebral microbleeds (CMB) on magnetic resonance imaging, clinical blood pressure (BP) level, traditional Chinese medicine (TCM) syndrome scores, mini-mental state examination (MMSE) scale, and safety outcomes. Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds on magnetic resonance imaging were tested before enrollment and after 6 months of treatment. The clinical blood pressure level, traditional Chinese medicine syndrome scores, mini-mental state examination scale and safety outcomes were tested before enrollment, after 3-month, 6-month treatment and 12th-month follow-up respectively. Conclusion: The protocol will comfirm whether naotaifang capsules reduce Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds, clinical blood pressure, increase mini-mental state examination scores, traditional Chinese medicine syndrome scores of Qi deficiency and blood stasis (QDBS), and improve the quality of life of subjects. The consolidated evidence from this study will shed light on the benefits of Chinese herbs for hypertensive cerebral small vessel disease, such as nourishing qi, promoting blood circulation and removing blood stasis, and dredging collaterals. However, additional clinical trials with large samples and long intervention periods will be required for in-depth research. Clinical Trial registration: www.chictr.org.cn, identifier ChiCTR1900024524.

Inhibition of the CEBPß-NFκB interaction by nanocarrier-packaged Carnosic acid ameliorates glia-mediated neuroinflammation and improves cognitive function in an Alzheimer's disease model.

Neuroinflammation occurs early in Alzheimer's disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aß clearance and disruption of synaptic connection. CEBPß, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPß-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPß facilitated the interaction of CEBPß with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1ß, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced ß-amyloid (Aß) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPß with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aß secretion by inhibiting the CEBPß-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEßCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEßCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.

Potent Neutralization Antibodies Induced by a Recombinant Trimeric Spike Protein Vaccine Candidate Containing PIKA Adjuvant for COVID-19.

The structures of immunogens that elicit the most potent neutralization antibodies to prevent COVID-19 infection are still under investigation. In this study, we tested the efficacy of a recombinant trimeric Spike protein containing polyI:C (PIKA) adjuvant in mice immunized by a 0-7-14 day schedule. The results showed that a Spike protein-specific antibody was induced at Day 21 with titer of above 50,000 on average, as measured by direct binding. The neutralizing titer was above 1000 on average, as determined by a pseudo-virus using monoclonal antibodies (40592-MM57 and 40591-MM43) with IC50 at 1 µg/mL as standards. The protein/peptide array-identified receptor-binding domain (RBD) was considered as immunodominant. No linear epitopes were found in the RBD, although several linear epitopes were found in the C-terminal domain right after the RBD and heptad repeat regions. Our study supports the efficacy of a recombinant trimeric Spike protein vaccine candidate for COVID-19 that is safe and ready for storage and distribution in developing countries.

An antibody-drug conjugate targeting a GSTA glycosite-signature epitope of MUC1 expressed by non-small cell lung cancer.

Antibodies targeting aberrantly glycosylated proteins are ineffective in treating cancer. Antibody-drug conjugates have emerged as effective alternatives, facilitating tumor-specific drug delivery. Previous studies have assessed the aberrantly glycosylated tandem repeat region of MUC1 glycoprotein as three site-specific glycosylated neoantigen peptide motifs (PDTR, GSTA, and GVTS) for binding with a monoclonal antibody. This study aimed to develop an antibody-drug conjugate for cancer treatment based on monoclonal antibodies against the aforementioned three neoantigen peptide motifs. Internalization of monoclonal antibodies was assessed via immunofluorescence staining and colocalization with lysosomal markers in live cells. Antibody positivity in tumor and peritumoral tissue samples was assessed via immunohistochemistry. The efficacy of anti-MUC1 ADCs was evaluated using various cancer cell lines and a mouse tumor xenograft model. An anti-MUC1 ADC was synthesized by conjugating GSTA neoantigen-specific 16A with monomethyl auristatin E (MMAE), which displayed potent antitumoral efficacy with an IC50 ranging 0.2-49.4 nM toward various cancer cells. In vivo, 16A-MMAE inhibited tumor growth in a dose-dependent manner in a mouse xenograft model established using the NCI-H838 NSCLC cell line, at a minimum effective dose of 1 mg/kg. At 3 mg/kg, 16A-MMAE did not cause significant toxicity in a transgenic mouse expressing human MUC1. The high antitumoral efficacy of 16A-MMAE suggests that aberrant glycosylated MUC1 neoantigen is a potential target for the development of ADCs for treating various cancers. Personalized therapy may be achieved through such glycosite-specific ADCs.

Diabetes mellitus and risk of brain tumors: A meta-analysis.

Accumulating evidence suggests that a history of diabetes may be involved in the occurrence of various types of cancer. However, the association of diabetes with the risk of brain tumors remains unclear. We identified relevant studies by performing a literature search of PubMed and EMBASE (through to 24 May 2012) and by searching the reference lists of pertinent articles. All data were extracted independently by two investigators using a standardized data abstraction tool. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Inter-study heterogeneity was assessed using the Cochran's Q and I(2) statistical tests. A total of 13 studies were included in this meta-analysis, including the entire Danish population, 5,107,506 other participants and more than 2,206 cases of brain tumors. In the analysis of these 13 studies, we observed that diabetic individuals had a similar risk of brain tumors as non-diabetic individuals (SRR, 1.12; 95% CI, 0.89-1.42). There was significant evidence of heterogeneity among these studies (P<0.001; I(2), 93.5%). Sub-group analysis revealed that diabetic females had a 24.2% increased risk of brain tumors (SRR, 1.242; 95% CI, 1.026-1.502), which was not observed in diabetic males. No significant publication bias was found in this study. The findings of this meta-analysis indicate that diabetic individuals have a similar risk of brain tumors as non-diabetic individuals. However, a significant positive correlation between the risk of brain tumors and diabetes mellitus was revealed in females, but not in males.

RhoA regulates invasion of glioma cells via the c-Jun NH2-terminal kinase pathway under hypoxia.

The purpose of this study was to investigate the mechanism of glioma cell invasion in hypoxic conditions. We demonstrated that hypoxia increased cell invasion, matrix metalloproteinase-2 (MMP2) activity and time-dependent expression of hypoxia inducible factor-1α (HIF-1α) in human glioma cells. These data suggest that MMP2 may play a significant role in tumor invasion in hypoxic conditions. We investigated the mechanisms involved in the increased MMP2 activity and cell invasion in hypoxic conditions. Increased expression of phospho-Jun NH2-terminal kinase (p-JNK) and phospho-c-Jun (p-c-Jun) in glioma cells induced by hypoxia was detected. Furthermore, this effect may be reduced by inhibiting the JNK signaling pathway. We found that inhibition of RhoA geranylgeranylation by geranylgeranyltransferase inhibitor-2147 (GGTI-2147) or knockdown of RhoA by siRNA against RhoA reduced the expression of p-JNK and p-c-Jun, and decreased MMP2 activity and glioma cell invasion in hypoxic conditions. These data suggest a link among RhoA, JNK, c-Jun and MMP2 activity that is functionally involved in the increased glioma cell invasion induced by hypoxia.

Analysis of the Causes and Progress in the Treatment of Impaired Maturation of Radio-cephalic Fistula for Haemodialysis / 现代生物医学进展

Radial-cephalic arteriovenous fistula (RCAVF) is considered the first choice for hemodialysis vascular access because of its high patency rate and less complications.But up to 50％ of the fistula can not mature.This is mainly due to persistent low blood flow or difficulty in cannulation can not lead to adequate hemodialysis.Inflow or outflow stenosis,anastomotic stenosis,exceedingly deep location of the vein,flow diversion into accessory veins are the common causes of impaired maturation.In addition,thrombosis is a common of stenosis.Preoperative assessment by physical examination and ultrasound examination of blood vessels,select the appropriate blood vessels for the fistula is of great significance.Choose the appropriate treatment for the cause of maturation disorders.Postoperative aspirin is widely used to prevent thrombosis and reduce the occurrence of stenosis;Surgery has the advantage of bypassing the damaged area but creating a new stoma;in recent years,endovascular technique because of its characteristics of minimally invasive in most of the time is the first choice.In this paper,the definition,etiology,diagnosis and treatment of fistula maturation disorder are reviewed.

The clinical analysises of percutaneous mechanical thrombectomy apply to vascular disease / 国际外科学杂志

For recently 30 years,with the progress of science,the development of intracavitary technology has been constantly improved and expanded.Reascularization technology makes the cure of vaso-occlusive disease a great leap.Because of its small trauma,repeatable,high security,near future curative effect,interventional therapy is distinctly superior to the traditional treatment such.Peripheral vascular lumen treatments including the balloon dilatation,stent-assisted angioplasty,catheter guided thrombolysis,and percutaneous mechanical thrombectomy,etc.Although angioplasty has become the best choice but the preferred treatment has limitations,such as for long and severe calcification of arteries occlusion surgery is difficult,immediate and long-term patency rate is low,the postoperative complications is frequent;Used for plaque ulcer and potentially thromboembolic disease,body highly risks of distal embolization;Inherent retraction force for postoperative lumen,intimal inflammation restenosis,stent thrombosis cause problems frequently.However,the percutaneous mechanical thrombectomy system is aimed at solving the clinical problems with good combination of engineering and technology research.The purpose of this paper is to expound the existing mechanical embolus removal system:SilverHawk/TurbjHawk aod Straub Rotarex thrombus,that is to elaborate its development status and clinical analysis.

Preoperative judging of T-staging of rectal cancer by transrectal biplane ultrasound / 中华超声影像学杂志

ObjectiveTo explore the accuracy of judging the T-staging of rectal cancer by biplane transrectal ultrasound.MethodsPathological enteroscopic biopsy was carried out for 197 cases of rectal cancer.Cases of middle and lower rectal cancer without serious obstruction were examined by means of transrectal biplane ultrasound through which to observe the changes of the echoes and to detect the depth of the infiltration in the intestinal walls and the presence of invasions in prostate glands,seminal in male or vesicles,uterine cervix in female.On the basis of the findings,the preoperative tumor staging was made.Postoperatively,the ultrasound results were compared with the pathological examination.Their consistency was evaluated by using Kappa test.ResultsTransrectal biplane ultrasound examination showed the total accuracy rate in T-staging of rectal cancer was as high as 83.8％ with the diagnostic sensitivity rate for T1to T4 as 77.8 ％,73.1％,89.3％ and 94.4％,while its diagnostic specificity rate degree was 97.3％,93.1 ％,85.1 ％,97.8％ respectively,The k -value was 0.732 which suggested that the ultrasound staging was highly consistent with the pathological staging(P＜0.05).ConclusionsTransrectal biplane ultrasound has a great value in the preoperative T-staging of rectal cancer and is helpful in the planning of treatment.