An Integrated Clinical and Computerized Tomography-Based Radiomic Feature Model to Separate Benign from Malignant Pleural Effusion.

INTRODUCTION: Distinguishing between malignant pleural effusion (MPE) and benign pleural effusion (BPE) poses a challenge in clinical practice. We aimed to construct and validate a combined model integrating radiomic features and clinical factors using computerized tomography (CT) images to differentiate between MPE and BPE. METHODS: A retrospective inclusion of 315 patients with pleural effusion (PE) was conducted in this study (training cohort: n = 220; test cohort: n = 95). Radiomic features were extracted from CT images, and the dimensionality reduction and selection processes were carried out to obtain the optimal radiomic features. Logistic regression (LR), support vector machine (SVM), and random forest were employed to construct radiomic models. LR analyses were utilized to identify independent clinical risk factors to develop a clinical model. The combined model was created by integrating the optimal radiomic features with the independent clinical predictive factors. The discriminative ability of each model was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: Out of the total 1,834 radiomic features extracted, 15 optimal radiomic features explicitly related to MPE were picked to develop the radiomic model. Among the radiomic models, the SVM model demonstrated the highest predictive performance [area under the curve (AUC), training cohort: 0.876, test cohort: 0.774]. Six clinically independent predictive factors, including age, effusion laterality, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase (NSE), were selected for constructing the clinical model. The combined model (AUC: 0.932, 0.870) exhibited superior discriminative performance in the training and test cohorts compared to the clinical model (AUC: 0.850, 0.820) and the radiomic model (AUC: 0.876, 0.774). The calibration curves and DCA further confirmed the practicality of the combined model. CONCLUSION: This study presented the development and validation of a combined model for distinguishing MPE and BPE. The combined model was a powerful tool for assisting in the clinical diagnosis of PE patients.

Obstructive sleep apnea hypopnea syndrome was a risk factor for uncontrolled hypertension in adult snorers in South China.

BACKGROUND: The association of obstructive sleep apnea hypopnea syndrome (OSAHS) with uncontrolled hypertension has not been fully investigated to date. The present article will investigate the associated factors of uncontrolled hypertension in South China Method: A total of 668 patients (531 males, 137 females) in South China were enrolled in this study. All patients completed questionnaires and then underwent an in-hospital polysomnography. RESULT: Univariate analysis showed that drinking, apnea-hypopnea index, Epworth Sleepiness Scale (ESS) index, the presence of OSAHS, MSaO2 and the lowest SaO2, circumference of neck and waist were predictors of uncontrolled hypertension. Multiple logistic regression analysis showed that ESS, presence of OSAHS, and the lowest SaO2 was independently associated with the risk for uncontrolled hypertension. CONCLUSION: The lowest SaO2, ESS index, and OSAHS were risk factors for uncontrolled hypertension.

[Analysis of clinical characteristics and risk factors of obstructive sleep apnea hypopnea syndrome with hypertension].

OBJECTIVE: To study the risk factors contributing to the development of hypertension in patients with obstructive sleep apnoea hypopnea syndrome (OSAHS), and the clinical characteristics of OSAHS with hypertension. METHODS: A total of 2397 OSAHS patients aged above 30 years old and diagnosed by the sleep-disordered breathing center of Guangxi between July 2012 and August 2015 were recruited. OSAHS patients with new-onset hypertension (OSAHS with hypertension group) and those without hypertension (simple OSAHS group) were identified and their clinical data, including general status, family history of hypertension or snoring, Epworth Sleepiness Scale (ESS) score for daytime sleepiness, physical examination findings, and polysomnography monitoring data were collected. OSAHS patients with new-onset hypertension (n=101) and OSAHS patients without hypertension (n=202) matched by age and body mass index (BMI) (age difference, 2 years; BMI difference, 1.5 kg/m(2)) were recruited in the OSAHS with hypertension group and the simple OSAHS group. A case-control study was used to compare the clinical characteristics of these two groups, and univariate and multivariate Logistic regression were used to analyze all the factors contributing to hypertension development besides age and BMI. RESULTS: The average age and BMI of the OSAHS with hypertension group and the simple OSAHS group were respectively (46.2±9.3), (46.2±9.2) years old and (28.2±2.8), (28.2±2.8) kg/m(2). Patients in the two groups were well-matched with respect to age and BMI (P>0.05). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the OSAHS with hypertension group were significantly higher than those in the simple OSAHS group at the first admission to the clinic and before and after the PSG examination. ESS values in the OSAHS with hypertension group and the simple OSAHS group were respectively 10.0±6.4 and 9.2±6.3 (P>0.05). There was no significant intergroup difference in neck circumference, waist circumference, duration of snoring, family history of snoring, and family history of hypertension (P>0.05) either. The apnea-hypopnea index (AHI) and apnea index (AI) in the OSAHS with hypertension group were higher than those in the simple OSAHS group (P<0.05); the longest apnea duration (LAD), mean apnea duration (MAD), and the total time spent with oxygen saturation below 90% (T90%) in the OSAHS with hypertension group were significantly longer than those in the simple OSAHS group (P<0.05). The minimal pulse oxygen saturation (MinSpO2) in the OSAHS with hypertension group was significantly lower than that in the simple OSAHS group (P<0.05). Six factors were identified to be associated with OSAHS with hypertension through univariate analysis: AHI (OR=0.985, P=0.001), AI (OR=0.983, P<0.001), LAD (OR=0.955, P=0.013), MAD (OR=0.874, P=0.015), MinSpO2 (OR=0.874, P=0.015), T90% (OR=0.997, P=0.036). Only MinSpO2 (P<0.001, OR=0.894) was closely related to OSAHS hypertension development in the multivariate Logistic regression model. CONCLUSIONS: OSAHS patients with hypertension may show lower MinSpO2, higher AHI and AI, and longer LAD, MAD, and T90% than OSAHS patients without hypertension. MinSpO2 is probably closely related to OSAHS hypertension development.

Targeting collagen damage for sustained in situ antimicrobial activities.

Antimicrobial peptides (AMPs) are promising anti-infective drugs, but their use is restricted by their short-term retention at the infection site, non-targeted uptake, and adverse effects on normal tissues. Since infection often follows an injury (e.g., in a wound bed), directly immobilizing AMPs to the damaged collagenous matrix of the injured tissues may help overcome these limitations by transforming the extracellular matrix microenvironment of the infection site into a natural reservoir of AMPs for sustained in situ release. Here, we developed and demonstrated an AMP-delivery strategy by conjugating a dimeric construct of AMP Feleucin-K3 (Flc) and a collagen hybridizing peptide (CHP), which enabled selective and prolonged anchoring of the Flc-CHP conjugate to the damaged and denatured collagen in the infected wounds in vitro and in vivo. We found that the dimeric Flc and CHP conjugate design preserved the potent and broad-spectrum antimicrobial activities of Flc while significantly enhancing and extending its antimicrobial efficacy in vivo and facilitating tissue repair in a rat wound healing model. Because collagen damage is ubiquitous in almost all injuries and infections, our strategy of targeting collagen damage may open up new avenues for antimicrobial treatments in a range of infected tissues.

Systematic review and meta-analysis of the correlation between plasma homocysteine levels and coronary heart disease.

Background: With the progresses in medical development in recent years, plasma homocysteine (Hcy) levels are considered to be an independent risk factor for the development of coronary heart disease (CHD). We hope to use the method of meta-analysis to systematically evaluate the relationship between plasma Hcy levels and CHD, for providing a basis for the prevention, diagnosis and treatment of CHD. Methods: The PubMed, Cochrane and Embase databases were searched for case-control studies and cohort studies on the association between plasma Hcy levels and CHD from the database establishment to October 2021. Duplicate studies were re-excluded by Endnote X9 software. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) scale. All of the studies we included were studies with no confirmed CHD and recorded Hcy levels. The data were extracted, and the quality was evaluated. Data were recorded and meta-analyzed using Stata 15.1 software. The risk ratio (RR) values were combined with 95% confidence interval (CI) using fixed- or random-effects models. Finally, sensitivity analysis was used to assess the reliability of the results. A funnel plot was used to evaluate the publication bias of the literature. Results: A total of 10 studies with a total of 10,103 subjects were included. All studies were of case-control studies or cohort studies with good quality. Meta-analysis showed that for every 5 µmol/L increase in Hcy level, the pooled risk ratio of coronary events was 1.22, 95% CI: 1.11, 1.34. These results demonstrate that when plasma Hcy level increased, the risk of CHD also increased. Conclusions: Compared with traditional risk factors, the incidence of CHD increases by 22% for every 5 µmol/L increase in plasma Hcy levels. This mean that clinicians can timely take preventive measures for coronary heart disease when the patients' elevated plasma Hcy.

Genetic variants in the RAB7L1 and SLC41A1 genes of the PARK16 locus in Chinese Parkinson's disease patients.

We performed direct DNA sequencing of the RAB7L1 and SLC41A1 genes within the PARK16 locus in 205 Chinese Parkinson's disease (PD) patients. Three novel heterozygous variants were identified in SLC41A1: c.436A > G (causing p.Lys146Glu), c.1440A > G (causing p.Pro480Pro), and c.552 + 50G > A. These three variants were not present in any of the 210 genetically unrelated healthy controls of the same ethnic origin. No changes were identified in the RAB7L1 gene. Additionally, for the eight core PARK16 SNPs, no significant difference in allele or genotype frequencies was observed between PD patients and controls. Further analysis is required to determine the role of genes within the PARK16 locus in development of PD.

A novel nonsense mutation in the NDP gene in a Chinese family with Norrie disease.

PURPOSE: Norrie disease (ND), a rare X-linked recessive disorder, is characterized by congenital blindness and, occasionally, mental retardation and hearing loss. ND is caused by the Norrie Disease Protein gene (NDP), which codes for norrin, a cysteine-rich protein involved in ocular vascular development. Here, we report a novel mutation of NDP that was identified in a Chinese family in which three members displayed typical ND symptoms and other complex phenotypes, such as cerebellar atrophy, motor disorders, and mental disorders. METHODS: We conducted an extensive clinical examination of the proband and performed a computed tomography (CT) scan of his brain. Additionally, we performed ophthalmic examinations, haplotype analyses, and NDP DNA sequencing for 26 individuals from the proband's extended family. RESULTS: The proband's computed tomography scan, in which the fifth ventricle could be observed, indicated cerebellar atrophy. Genome scans and haplotype analyses traced the disease to chromosome Xp21.1-p11.22. Mutation screening of the NDP gene identified a novel nonsense mutation, c.343C>T, in this region. CONCLUSIONS: Although recent research has shown that multiple different mutations can be responsible for the ND phenotype, additional research is needed to understand the mechanism responsible for the diverse phenotypes caused by mutations in the NDP gene.

Novel mutations of the SPG11 gene in hereditary spastic paraplegia with thin corpus callosum.

BACKGROUND: Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a clinically and genetically heterogeneous neurodegenerative disorder with genetic linkage to multi-loci. Recently pathogenic mutations in the KIAA1840 (now named SPG11) for SPG11, the major HSP-TCC locus, were identified; at least 42 different mutations have been detected. OBJECTIVE: To study the clinical features and identify the SPG11 gene mutations in Chinese patients with HSP-TCC. METHODS: Three kindreds with an autosomal recessive HSP-TCC and 5 cases with sporadic HSP-TCC in Chinese Hans were recruited. Detailed clinical history, neurological examination, MRI, electromyography, Mini Mental State Examination (MMSE), Spastic Paraplegia Rating Scale (SPRS) were presented. DNA samples of the 8 families were collected and mutation analysis of SPG11 gene was carried out by direct DNA sequencing. RESULTS: Except for one patient whose age at onset was 3 years old, 10 patients manifested a relatively similar combination of adolescence-onset cognitive decline and spastic paraparesis with TCC on brain MRI. We identified 10 novel and one known mutations in our 8 HSP-TCC families, which were two nonsense mutations (c.5977C>T/p.Q1993X, c.4668T>A/p.Y1556X), three small deletions (c.6898_6899delCT/p.L2300AfsX2338, c.3719_3720delTA/p.I1240VfsX263, c.733_734delAT/p.M245VfsX246), four small insertions (c.7088_7089insATTA/p.Y2363X, c.2163_2164insT/p.I722YfsX731, c.7101_7102insT/p.K2368X, c.6790_6791insC/p.L2264PfsX2339), one deletion/insertion (c.654_655delinsG/p.S218RfsX219), and one splice mutation (c.7151+4_7151+7delAGTA/p.K2384fsX2386). Each family has a different mutation and all the mutations are predicted to cause early protein truncation. CONCLUSION: This study widens the mutation spectrum of the SPG11 gene and the mutations in the SPG11 gene are also the major causative gene for HSP-TCC in the Chinese Hans. Screening of the whole gene is recommended in clinical practice.

[Endobronchial eosinophils preferentially stimulate T helper cell type 2 responses].

OBJECTIVE: The aim of the present study was to evaluate whether eosinophils within the tracheobronchial lumen can stimulate Th2 cell expansion by presenting antigen both in vitro and in vivo. METHODS: Airway eosinophils were recovered from ovalbumin-sensitized and -challenged BALB/c mice, these eosinophils were then cocultured with sensitized CD4(+) cells in the absence or presence of anti-CD80 or/and -CD86 monoclonal antibodies. Airway eosinophils were instilled into the trachea of sensitized mice, At 3 d thereafter, the draining paratracheal lymph nodes were removed and teased into cell suspensions for culture. Cell-free culture supernatants were collected for detection of cytokines. RESULTS: Our data showed that airway eosinophils, recovered following inhalational ovalbumin challenge in sensitized mice functioned as CD80- and CD86-dependent antigen-presenting cells to stimulate sensitized CD4(+) lymphocytes to produce IL-4, IL-5 and IL-13, but not interferon-gamma (IFN-gamma) in vitro assay. When instilled intratracheally in ovalbumin-sensitized recipient mice, these antigen-loaded eosinophils migrated into draining paratracheal lymph nodes primed Th2 cells in vivo for IL-4, IL-5 and IL-13, but not IFN-gamma, production during the in vitro culture that was also CD80- and CD86-dependent. CONCLUSIONS: We concluded that eosinophils within the lumina of airways could process inhaled antigen function in vitro and in vivo as antigen-presenting cells to promote expansion of Th2 cells. This investigation highlights the potential of eosinophils to not only act as terminal effector cells but also to actively modulate immune responses by amplifying Th2 cell responses.

An association between the PARK16 locus and Parkinson's disease in a cohort from eastern China.

Genome-wide association studies (GWAS) have identified several single-nucleotide polymorphisms (SNPs) at the PARK16 locus that can modulate the risk of Parkinson's disease (PD), including rs16856139, rs823128, rs823122, rs947211, rs823156, rs708730 and rs11240572. The strength of these associations has been investigated in people from several ethnic origins, including Europe, Chile, Japan, Taiwan and western China. The results have shown that an ethnicity-specific effect is an important consideration in such an analysis. Therefore, we genotyped the above seven SNPs using a case-control methodology to explore their association with the risk of PD in eastern China. A total of 456 study subjects comprising 226 patients with PD and 230 unrelated healthy controls were recruited. The minor allele frequencies at the rs16856139 and rs11240572 SNPs were found to be significantly higher in controls than in PD cases, which suggested that they conferred a protective effect against PD. Further analyses from more diverse ethnic origins are required to confirm the significance of rs16856139 and rs11240572.

Genetic screening for mutations in the Nrdp1 gene in Parkinson disease patients in a Chinese population.

Strong evidence has shown that a defect in the Parkin gene is known to be a common, genetic cause of Parkinson disease (PD). The E3 ubiquitin ligase Nrdp1 is shown to interact with the N terminal of Parkin (the first 76 amino acids) and catalyze degradation of Parkin via the ubiquitin-proteasome pathway, suggesting that Nrdp1 may be involved in the development of PD via the regulation of Parkin, We believe we are the first to have screened PD patients for mutations in the Nrdp1 gene to determine the association between these variants and PD. By direct sequencing, we analysed the entire coding regions and 5' UTR of Nrdp1 in 209 Chinese PD patients and 302 unrelated healthy individuals. No variant was detected in the coding regions (exons 3-7); only 2 variants (c.-206 T > A and c.-208-8 A > G) were identified in the 5' UTR (exon 2) and intron 1. Furthermore, a study of the allelic and genotypic association between patients and controls showed no significant association between the c.-206 T > A polymorphism and PD; c.-208-8 A > G was identified in one PD patient and not in controls. Our data do not support the hypothesis of a major role for the Nrdp1 gene in PD development in the Chinese population.

Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population.

OBJECTIVES: Autism is a neurodevelopmental disorder, and genetic factors play an important role in its pathogenesis. Earlier findings suggest the CNTNAP2 as a predisposition locus of autism, but no study has been carried out on the possible association of CNTNAP2 with autism in the Chinese Han population. METHODS: In this study, three single nucleotide polymorphisms located within the CNTNAP2 were genotyped in 185 Chinese Han autistic families by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by a transmission disequilibrium test. RESULTS: The results show that a common noncoding variant (rs10500171) is associated with the increased risk for autism, and haplotype T-A (rs7794745- rs10500171, P=0.011) and haplotype A-T-A (rs10244837- rs7794745- rs10500171, P=0.032) also showed evidence of association. CONCLUSION: The results of family-based association study suggested that the CNTNAP2 is a susceptibility gene of autism in the Chinese Han population.

Soluble CTLA-4 in sera of patients with bronchial asthma.

Cytotoxic lymphocyte associated antigen-4 (CTLA-4) is a homologue of CD28, which plays a critical role in the down-regulation of antigen-activated immune response. The aim of the present study was to investigate the concentrations of soluble CTLA-4 in sera of patients with bronchial asthma and the correlation between soluble CTLA-4 concentrations and some clinical measures of asthma. The concentrations of serum soluble CTLA-4 in 31 atopic asthmatics, 20 non-atopic asthmatics, and 28 non-atopic normal control volunteers were determined by ELISA technique, and the relationship between serum soluble CTLA-4 concentrations in asthmatics and airway responsiveness, pulmonary function, blood white cell counts and differentials, respectively, were analyzed. Serum soluble CTLA-4 concentrations in both atopic asthmatics (20.2 +/- 5.4 microg/L) and non-atopic asthmatics (19.2 +/- 6.2 microg/L) were all higher than that in normal controls (1.8 +/- 0.8 microg/L, p = 0.04 and 0.014, respectively). There was no difference in serum soluble CTLA-4 concentrations between atopic and non-atopic asthmatics (p = 0.877). The serum soluble CTLA-4 concentrations in the asthmatics statistically correlated with forced expiratory volume in one second (r = -0.410, p = 0.027), percentage of predicted peak expiratory flow (r = -0.449, p = 0.015), and PaCO2 (r = 0.555, p = 0.002), respectively. Our data also showed that the concentration of soluble CTLA-4 was significantly related to blood lymphocyte numbers. The serum soluble CTLA-4 protein level was significantly elevated in patients with asthma. This level correlated with the severity of asthma. Our data also showed that the concentration of soluble CTLA-4 was significantly related to blood lymphocyte numbers.