A deep learning framework for predicting disease-gene associations with functional modules and graph augmentation.

BACKGROUND: The exploration of gene-disease associations is crucial for understanding the mechanisms underlying disease onset and progression, with significant implications for prevention and treatment strategies. Advances in high-throughput biotechnology have generated a wealth of data linking diseases to specific genes. While graph representation learning has recently introduced groundbreaking approaches for predicting novel associations, existing studies always overlooked the cumulative impact of functional modules such as protein complexes and the incompletion of some important data such as protein interactions, which limits the detection performance. RESULTS: Addressing these limitations, here we introduce a deep learning framework called ModulePred for predicting disease-gene associations. ModulePred performs graph augmentation on the protein interaction network using L3 link prediction algorithms. It builds a heterogeneous module network by integrating disease-gene associations, protein complexes and augmented protein interactions, and develops a novel graph embedding for the heterogeneous module network. Subsequently, a graph neural network is constructed to learn node representations by collectively aggregating information from topological structure, and gene prioritization is carried out by the disease and gene embeddings obtained from the graph neural network. Experimental results underscore the superiority of ModulePred, showcasing the effectiveness of incorporating functional modules and graph augmentation in predicting disease-gene associations. This research introduces innovative ideas and directions, enhancing the understanding and prediction of gene-disease relationships.

CYP2C19 *2/*2 Genotype is a Risk Factor for Multi-Site Arteriosclerosis: A Hospital-Based Cohort Study.

Background: Vascular diseases such as atherosclerosis usually affect multiple organs. Genetic factors have a certain proportion in the risk factors of atherosclerosis. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with multi-site atherosclerosis. Methods: The study included 410 patients with single-site atherosclerosis and 529 patients with multi-site atherosclerosis. The relationship between CYP2C19 rs4244285 and rs4986893 polymorphisms and single-site atherosclerosis and multi-site atherosclerosis was analyzed. Results: The proportion of CYP2C19 rs4244285 A allele (35.9% vs 29.9%, P=0.007) and rs4986893 G allele (97.7% vs 94.8%, P=0.001) in multi-site atherosclerosis group was significantly higher than that in single-site atherosclerosis group. The distribution of CYP2C19 genotypes was significantly different between the two groups (P=0.002). The results of univariate logistic regression indicated that CYP2C19 *1/*3 genotype (*1/*3 vs *1/*1: odds ratio (OR) 0.456, 95% confidence interval (CI): 0.231-0.902, P=0.024) may decrease risk of multi-site atherosclerosis, while *2/*2 genotype (*2/*2 vs *1/*1: OR 1.780, 95% CI: 1.100-2.880, P=0.019) may increase risk of multi-site atherosclerosis. Multivariate logistic regression (adjusted for gender, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 *1/*3 genotype (*1/*3 vs *1/*1: OR 0.459, 95% CI: 0.231-0.909, P=0.026) may be an independent protective factor for multi-site atherosclerosis, while *2/*2 genotype (*2/*2 vs *1/*1: OR 1.767, 95% CI: 1.091-2.864, P=0.021) may be an independent risk factor for multi-site atherosclerosis. Conclusion: CYP2C19 *1/*3 genotype may be an independent protective factor for multi-site atherosclerosis, while *2/*2 genotype may be an independent risk factor for multi-site atherosclerosis.

Effects and mechanisms of intrauterine chronic hypoxia on ovarian reserve function of zygotic rats.

Chronic intrauterine hypoxia (ICH) may lead to permanent alterations in the offspring's body structure, function, and metabolism through the "developmental programming" pathway, resulting in lasting changes in physiology and metabolism, as well as the onset of adult-onset diseases. The aim was to investigate intrauterine growth restriction caused by ICH and its effect on ovarian reserve function in female offspring at different developmental stages after birth. Healthy female Sprague-Dawley rats (n = 20) were pregnant by normal mating, and the rats in the ICH group were treated with chronic intrauterine hypoxia twice a day for 04 h00 each time from day 4 to 21 of gestation. After the first hypoxic treatment, four pregnant rats were randomly selected from the ICH and natural control groups for arterial blood gas analysis. In the ICH group, birth weight and body weight on the 5th day after birth were less than in the control group, the total number of follicles and the number of primordial follicles in the offspring of the ICH group were significantly reduced on postnatal days 5, 20, and 40 (p < 0.05). ICH decreases ovarian reserve function in female offspring rats and programmatically regulates the differential expression of ovarian miRNAs in female offspring rats.

The Value of Ultrasonic Elastography in Detecting Placental Stiffness for the Diagnosis of Preeclampsia: A Meta-Analysis.

This meta-analysis evaluated the diagnostic value of ultrasonic elastography in detecting placental stiffness in the diagnosis of preeclampsia (PE). A systematic search was conducted in the EMBASE, Web of Science, Cochrane Library, Scopus database, and PubMed databases to identify studies published before June 2023 using ultrasonic elastography to diagnose PE. The sensitivity, specificity, and diagnostic odds ratio of ultrasonic elastography for diagnosing PE were calculated, and a summary receiver operating characteristic curve model was constructed. The degree of heterogeneity was estimated using the I2 statistic, and a meta-regression analysis was performed to explore its sources. A protocol was determined previously (PROSPERO: CRD42023443646). We included 1188 participants from 11 studies, including 190 patients with PE and 998 patients without PE as controls. Overall sensitivity and specificity of ultrasonic elastography in detecting placental stiffness for the diagnosis of PE were 89% (95% CI: 85-93) and 74% (95% CI: 51-89), respectively. The I2 values for sensitivity and specificity were 59% (95% CI: 29-89) and 96% (95% CI: 95-98), respectively. The area under the receiver operating characteristic curve was 0.90 (95% CI: 0.87-0.92). The meta-regression analysis showed no significant heterogeneity. Ultrasonic elastography exhibits good diagnostic accuracy for detecting placental stiffness and can serve as a non-invasive tool for differentially diagnosing PE.

ALDH2 rs671 Polymorphism Likely a Risk Factor for Hemorrhagic Stroke: A Hospital-Based Study.

Background: Hypertension is the main risk factor for hemorrhagic stroke. Aldehyde dehydrogenase 2 (ALDH2) may inhibit the occurrence of hypertension by anti-oxidative stress and vascular dilation. The purpose was to investigate the relationship of ALDH2 polymorphisms with hemorrhagic stroke in Hakka Chinese. Methods: A total of 329 patients with hemorrhagic stroke and 515 controls were enrolled, and medical records (smoking and drinking history, hypertension, and diabetes) were collected. The genotypes of ALDH2 rs671 of the two groups were detected and analyzed. Results: The proportion of the ALDH2 rs671 G/G, G/A, and A/A genotype in patients with hemorrhagic stroke was 55.9%, 37.4%, and 6.7%, respectively, while those were 65.0%, 30.7%, and 4.3% in controls, respectively. There was statistically significant difference in ALDH2 rs671 genotypes distribution (P=0.021) and alleles distribution (P=0.005) between patients and controls. Among hemorrhagic stroke patients, no statistically significant differences were observed between patients with ALDH2 different genotypes. Logistic regression analysis showed that there was significantly high risk of hemorrhagic stroke in men (male vs female: adjusted OR 1.711, 95% CI 1.154-2.538, P=0.008), the presence of hypertension (with vs without hypertension: adjusted OR 16.095, 95% CI 10.958-23.641, P<0.001), and the presence of ALDH2 rs671 G/A genotype (G/A vs G/G: adjusted OR 1.679, 95% CI 1.151-2.450, P=0.007) or A/A genotype (A/A vs G/G: adjusted OR 2.516, 95% CI 1.132-5.591, P=0.024). Conclusion: ALDH2 rs671 polymorphism likely a risk factor for hemorrhagic stroke.

Primary retroperitoneal angiosarcoma: A case report.

Angiosarcoma is a rare subtype of soft tissue sarcoma with identifiable vascular differentiation. It can occur at any age and develop throughout the body, but it is most commonly found in skin, soft, and breast tissues. Primary retroperitoneal angiosarcoma is rarely reported in the relevant literature. This article reports a case of primary retroperitoneal angiosarcoma in a middle-aged man, with the relevant literature reviewed in detail. A 46-year-old male had experienced left waist pain for 2 months. An ultrasonic examination revealed a mass in the left retroperitoneum, and left retroperitoneal lesions were confirmed via computed tomography (CT) and magnetic resonance imaging (MRI). The tumor was removed surgically, and the CT scan revealed local tumor recurrence after 1 month when the first adjuvant therapy was performed. The patient died of a massive hemorrhage from a ruptured tumor. Angiosarcoma has high malignancy and a poor prognosis. Its early diagnosis and treatment significantly impact the long-term survival rate of patients.

Ultrasound Guided Intra-Articular Injection of Triptolide-loaded Solid Lipid Nanoparticle for Treatment of Antigen-Induced Arthritis in Rabbits.

Objective: To evaluate the efficacy of ultrasound-guided intra-articular injection of triptolide-loaded solid lipid nanoparticle (TP-SLN) for treatment of antigen-induced arthritis (AIA) in rabbits. Material and Methods: Knee joints of 33 New Zealand rabbits with AIA were injected intra-articularly with triptolide (TP: n = 7), TP-SLN (n = 7), betamethasone (BS: n = 7) and dimethyl sulfoxide (DMSO: n = 6). The remaining six rabbits were untreated as the control group. The injection therapy in intervention groups was initiated 1 week after the last immunization in order to avoid irreversible joint damage in the later induction. The ultrasonic scores of the joints were assessed based on synovitis, synovial blood flow and bone erosion. Meanwhile, the correlations of ultrasonic scores and pathological scores were determined. The efficacy and side effects of each group were determined by combining ultrasonic scores, pathological scores, behavior, appetite, weight, joint diameter, skin temperature and biochemical examination. Results: 1) Compared with the control group, the diameters of knee joints of the TP, TP-SLN and BS groups began to reduce 1 week after intra-articular injection (p < 0.01). 2) With the exception of the DMSO group, the interventions were effective in treating synovitis compared with the control group, with TP-SLN and BS being the best. The ultrasonic and pathological scores in synovitis of the TP group were lower than that of model group (Z = -2.726 and -2.530, p < 0.05). The ultrasonic scores differed significantly between BS group and TP-SLN group (Z = -2.17 and -2.360, respectively, p < 0.05) and pathological scores (Z = -2.687 and -2.082, respectively, p < 0.05). 3) Compared with the control group, the TP, BS and TP-SLN were all effective in treating synovial blood flow and bone erosion and there were no significant differences of ultrasonic and pathological scores among them (p > 0.05). The ultrasonic scores of synovial blood flow (Z = -3.033, -2.842, -3.277, p < 0.01) were lower than in the controls. The ultrasonic scores (Z = -2.948, -3.141, -3.210, p < 0.01) and pathological scores (Z = -2.216, -2.505, -2.505, p < 0.05) of bone erosion were also lower than in the model group.4) There were significant correlations between the ultrasonic and pathological scores of synovial inflammation and bone erosion (r = 0.832 and 0.859 respectively, p < 0.001). Conclusions: The therapeutic effect of TP-SLN on arthritis is better than that of TP, but there is no difference between BS and TP-SLN. Therefore, TP-SLN may be used as an alternative to BS in the treatment of rheumatoid arthritis in the future. The ultrasonic and pathological scores showed significant correlation in synovitis and bone erosion. Ultrasound can provide a useful assessment of synovitis in early arthritis.

Critical Care Resources in Guangdong Province of China: Three Surveys from 2005 to 2015.

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.

Enhancement of hepatitis B surface antigen production by adenosine 5'-monophosphate in culture of recombinant Chinese hamster ovary cells.

Adenosine 5'-monophosphate was found effective in enhancing hepatitis B surface antigen (HBsAg) production in the culture of recombinant Chinese hamster ovary (CHO) cells, but it markedly inhibited cell growth. A culture strategy with periodical medium changes was established to increase HBsAg production and avoid the AMP-induced inhibition of cell growth. The enhanced energy supply might be one of the reasons for the increase in HBsAg production in the presence of AMP.