D-CyPre: a machine learning-based tool for accurate prediction of human CYP450 enzyme metabolic sites.

The advancement of graph neural networks (GNNs) has made it possible to accurately predict metabolic sites. Despite the combination of GNNs with XGBOOST showing impressive performance, this technology has not yet been applied in the realm of metabolic site prediction. Previous metabolic site prediction tools focused on bonds and atoms, regardless of the overall molecular skeleton. This study introduces a novel tool, named D-CyPre, that amalgamates atom, bond, and molecular skeleton information via two directed message-passing neural networks (D-MPNN) to predict the metabolic sites of the nine cytochrome P450 enzymes using XGBOOST. In D-CyPre Precision Mode, the model produces fewer, but more accurate results (Jaccard score: 0.497, F1: 0.660, and precision: 0.737 in the test set). In D-CyPre Recall Mode, the model produces less accurate, but more comprehensive results (Jaccard score: 0.506, F1: 0.669, and recall: 0.720 in the test set). In the test set of 68 reactants, D-CyPre outperformed BioTransformer on all isoenzymes and CyProduct on most isoenzymes (5/9). For the subtypes where D-CyPre outperformed CyProducts, the Jaccard score and F1 scores increased by 24% and 16% in Precision Mode (4/9) and 19% and 12% in Recall Mode (5/9), respectively, relative to the second-best CyProduct. Overall, D-CyPre provides more accurate prediction results for human CYP450 enzyme metabolic sites.

Knowledge, attitude, and practice toward weight management among diabetic patients in Qidong City, Jiangsu Province.

BACKGROUND: Weight management is an effective prevention and treatment strategy for diabetes mellitus. This study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic patients towards weight management. METHODS: Diabetic patients treated at Qidong City, Jiangsu Province, between January 2023 and June 2023 were included in this cross-sectional study. A self-designed questionnaire was used to collect their demographic characteristics and KAP toward weight management. Structural equation modeling (SEM) was employed to examine the inter-relationships among KAP scores. RESULTS: Among a total of 503 valid questionnaires that were collected, 55.07% were filled out by men and 54.67% by those aged < 60 years. The mean scores for knowledge, attitude, and practice were 8.03 ± 3.525 (possible range: 0-13), 31.88 ± 3.524 (possible range: 10-50), and 22.24 ± 3.318 (possible range: 9-45), respectively. Pearson's correlation analysis revealed the knowledge was positively associated with attitude (r = 0.295, P < 0.001) and practice (r = 0.131, P < 0.001), and attitude was positively associated with practice (r = 0.140, P = 0.002). SEM demonstrated positive associations between knowledge and attitude (ß = 0.28, P < 0.001), and attitude and practice (ß = 0.09, P = 0.019). Moreover, older age was negatively associated with knowledge (ß=-0.04, P = 0.001), while higher education (ß = 1.220, P < 0.001), increased monthly income (ß = 0.779, P < 0.001), diagnosis of fatty liver (ß = 1.03, P = 0.002), and screening for excess visceral fat (ß = 1.11, P = 0.002) were positively associated with knowledge. CONCLUSION: Diabetic patients showed moderate knowledge, neutral attitudes, and inappropriate practices toward weight management. Knowledge was positively associated with attitude and practice. These findings provided valuable directions for healthcare interventions targeting improved KAP status of weight management among diabetic patients.

Identification of Chemical Constituents in Blumea balsamifera Using UPLC-Q-Orbitrap HRMS and Evaluation of Their Antioxidant Activities.

Blumea balsamifera (L.) DC., a perennial herb in the Asteraceae family native to China and Southeast Asia, has a notable history of medicinal use due to its pharmacological properties. Using UPLC-Q-Orbitrap HRMS techniques, we systematically investigated the chemical constituents of this plant. A total of 31 constituents were identified, of which 14 were flavonoid compounds. Significantly, 18 of these compounds were identified in B. balsamifera for the first time. Furthermore, the mass spectrometry fragmentation patterns of significant chemical constituents identified in B. balsamifera were analyzed, providing important insights into their structural characteristics. The in vitro antioxidative potential of the methanol extract of B. balsamifera was assessed using DPPH and ABTS free-radical-scavenging assays, total antioxidative capacity, and reducing power. The antioxidative activity exhibited a direct correlation with the mass concentration of the extract, with IC50 values of 105.1 ± 0.503 µg/mL and 12.49 ± 0.341 µg/mL for DPPH and ABTS, respectively. For total antioxidant capacity, the absorbance was 0.454 ± 0.009 at 400 µg/mL. In addition, the reducing power was 1.099 ± 0.03 at 2000 µg/mL. This study affirms that UPLC-Q-Orbitrap HRMS can effectively discern the chemical constituents in B. balsamifera, primarily its flavonoid compounds, and substantiates its antioxidative properties. This underscores its potential utility as a natural antioxidant in the food, pharmaceutical, and cosmetics sectors. This research provides a valuable theoretical basis and reference value for the comprehensive development and utilization of B. balsamifera and expands our understanding of this medicinally valuable plant.

Identification of potential biomarkers for diagnosis of syphilis from the cerebrospinal fluid based on untargeted metabolomic analysis.

The infection rate of syphilis continues to rise globally, and the difficulty in diagnosis of neurosyphilis promptly needs to be resolved. More specific and sensitive diagnostic markers for latent syphilis and neurosyphilis should be found. Here the metabolic profiles of 88 cerebrospinal fluid samples from syphilis patients and controls were analyzed by LC/MS-based untargeted metabolomics. In total, 272 metabolites based on 3937 features obtained in ESI- mode and 252 metabolites based on 3799 features in ESI+ mode were identified. The experimental process was evaluated by principal component analysis, partial least squares discriminant analysis, and hierarchical cluster analysis. A clear separation between latent syphilis and neurosyphilis was found. Levels of lipid and linoleic acid metabolites, such as 9-oxo-octadecadienoic acid and 9,10,13-trihydroxyoctadecenoic acid, were increased in syphilis patients. In patients with neurosyphilis, significant changes in levels of 5-hydroxy-L-tryptophan (5-HTP) and acetyl-N-formyl-5-methoxykynurenamine (AFMK) in the tryptophan-kynurenine pathway were also detected. Only one metabolite, theophylline, differed significantly between symptomatic and asymptomatic neurosyphilis patients. Additionally, KEGG analysis revealed significant enrichment of tryptophan metabolism pathways, indicating a high correlation between tryptophan metabolism and syphilis symptoms. Levels of linoleic acid metabolites, 5-HTP, AFMK and theophylline were significantly altered in different patients. The role of these differential metabolites in the development of syphilis is worthy of further exploration. Our results may promote the development of biomarkers for diagnosis of latent syphilis from neurosyphilis, and for that of asymptomatic neurosyphilis from symptomatic neurosyphilis in the future.

Value of 3D ultrasound flow imaging combined with serum AFP, ß-hCG, sFlt-1 and CK in the diagnosis of placenta accreta.

PURPOSE: To analyze the diagnostic value of placenta three-dimensional (3D) energy blood flow parameters combined with maternal serum AFP, ß-hCG, sFlt-1 and CK levels for PA. METHODS: 30 pregnant women with PA and 30 pregnant women with normal placenta were randomly selected in the Affiliated Maternal and Child Health Hospital of Nantong University from January 2021 to December 2021. Thereafter, the 3D energy ultrasound was applied to detect the placenta VI, FI and VFI. Moreover, the diagnostic value of different parameters combined with serum AFP, ß-hCG, sFlt-1 and CK levels for PA was analyzed. RESULTS: Multivariate analysis results indicated that, gravidity > 2 and with/without placenta previa were the independent risk factors for PA (P < 0.05). In PA group, the AFP, ß-hCG, CK, placenta VI, FI and VFI values were higher than those in non-PA group, while sFlt-1 was apparently lower than that in non-PA group. With the increase in PA degree, the serum AFP, ß-hCG and CK levels increased. Meanwhile, serum sFlt-1 level was negatively correlated with PA degree. Serum AFP, ß-hCG, sFlt-1, CK and placenta VFI showed prediction potency for PA, and their combined detection attained the optimal diagnostic value for predicting PA. ROC curve analysis suggested that, serum AFP, ß-hCG, sFlt-1, CK and 3D ultrasound VFI value had the greatest AUC values in predicting PA, which might provide reference for the clinical diagnosis and disease evaluation of PA. Conclusion Serum AFP, ß-hCG, sFlt-1, CK and placental VFI can increase the consistency in the diagnosis of PA. Serum markers combined with 3D ultrasound blood flow imaging can improve the sensitivity and specificity of prenatal diagnosis of PA, which provides an important reference for clinical diagnosis and treatment.

Effects of vaginal microecology and immunity on the pregnancy outcome of cervical cerclage.

OBJECTIVE: To investigate the effects of vaginal microecology and immune status on the pregnancy outcome of cervical cerclage. METHODS: The clinical data of 125 patients with cervical incompetence who underwent transvaginal cervical cerclage in our hospital from January 2018 to January 2021 were collected, based on which the associations of vaginal microecology and related immune cytokines (IL-1ß, IL-6, IL-8 and TNF-α) with the cervical cerclage outcome were explored. RESULTS: All of the 125 patients had singleton pregnancies, who were aged 20-43 years, with a mean of (32.34 ± 5.17) years. The surgery was successful in 104 patients (full-term delivery or survival of premature infants), while unsuccessful in 21 patients (late miscarriage or death of premature infants), revealing a success rate of 83.20%. There were 70 full-term deliveries, 34 premature deliveries (28 survived while 6 died), and 15 late miscarriages. Univariate analysis revealed statistically significant differences in the timing of surgery, gestational age of cerclage, preoperative cervical canal length, genital tract infections and preoperative invasive procedures between the successful and unsuccessful groups (P < 0.05). Insignificant differences were found in the pre-pregnancy body mass index (BMI) (P > 0.05). According to the multivariate analysis results, cerclage timing and genital tract infections were independent risk factors for postoperative pregnancy failure (P < 0.05). The pathogen detection rates in the two groups of pregnant women were analyzed, finding significantly higher incidence of bacterial vaginosis (BV) in the unsuccessful group than in the successful group (P < 0.05). Inter-group comparison revealed that the positive rates for vaginal microenvironmental factors (LE, NAG, SNA, H2O2 and pH) were all significantly higher in the unsuccessful group than in the successful group (P < 0.05). Besides, the immune cytokine levels in the cervicovaginal secretions were also all significantly higher in the unsuccessful group than in the successful group (P < 0.05). CONCLUSION: The pregnancy outcome of patients undergoing cervical cerclage is associated with the imbalance of vaginal microecology and the levels of IL-1ß, IL-6, IL-8 and TNF-α in cervicovaginal secretions.

Perioperative management of a patient with a giant ovarian tumor: A case report.

RATIONALE: Giant ovarian tumors are very rare. Patients with large ovarian tumors appear similar to pregnant women and morbidly obese patients. The management of such patients is associated with significant mortality. Therefore, additional clinical research is essential to understanding the perioperative complications of this disease. PATIENT CONCERNS: We report the perioperative management of a patient with a giant ovarian tumor that contained 23 L of fluid who underwent tumor resection. Given the infrequency of these giant ovarian tumors, a detailed anesthetic plan and postoperative respiratory support strategy were tailored to address the patient's hemodynamic and respiratory risks, as well as to minimize potential complications, including supine hypotensive syndrome, re-expansion pulmonary edema, and postoperative intestinal ileus. To prevent supine hypotensive syndrome, the patient used a mild left-sided position (10∼20°) after admission until the tumor was removed. In order to prevent re-expansion pulmonary edema (RPE), the intraoperative ventilator mode was set to pressure-controlled ventilation (PCV), with the addition of 8 cmH2O positive end-expiratory pressure (PEEP). The airway pressure was lower while maintaining a certain tidal volume. In the ICU, in the ventilator mode, we use pressure support ventilation as well as PEEP and adjust it according to the patient's spontaneous breathing situation and blood gas analysis to prepare for further detach from the respirator and extubation. And we prevent the occurrence of postoperative intestinal ileus by placing the abdominal binder after the operation. DIAGNOSIS: Mucinous cystadenoma of the left ovary. INTERVENTIONS: The patient underwent exploratory laparotomy with debulking of the left ovarian mass, transabdominal hysterectomy with bilateral salpingo-oophorectomy, complete omentectomy with appendectomy, and pelvic lymphadenectomy. OUTCOMES: After surgery, the patient experienced intestinal distention. Up to now, the patient has recovered well. LESSONS: A multidisciplinary approach is essential. Knowing the possibility of complications and choices for management can lead to favorable outcomes in such rare cases. This case reminds us that postoperative complications such as postoperative intestinal ileus may be fatal.

Elevation of Cerebrospinal Fluid Light and Heavy Neurofilament Levels in Symptomatic Neurosyphilis.

BACKGROUND: Although clinical manifestations of symptomatic and asymptomatic neurosyphilis are different, few laboratory tests could reflect the difference. METHODS: A total of 92 non-HIV-infected patients with syphilis were enrolled in this study, including 23 with symptomatic neurosyphilis, 51 with asymptomatic neurosyphilis, and 18 with latent syphilis, which were excluded neurosyphilis because they were found to have no symptom and normal cerebrospinal fluid (CSF) tests and served as the control group. The concentrations of neurofilament light subunit (NF-L) and phosphorylated neurofilament heavy subunit (pNF-H) in the CSF were measured and compared among these groups, as well as before and after treatment in the symptomatic and asymptomatic groups. RESULTS: The median concentrations of NF-L in the symptomatic neurosyphilis, asymptomatic neurosyphilis, and control groups were 5806, 218, and 266 pg/mL, respectively (P < 0.001), and the median concentrations of pNF-H were 986, 43, and 49 pg/mL, respectively (P < 0.001). A subgroup of 15 symptomatic neurosyphilis and 10 asymptomatic neurosyphilis patients were followed up and underwent CSF examination 6 months after the antineurosyphilis treatment. The median concentration of NF-L in the symptomatic neurosyphilis group decreased from baseline 6420 to 2914 pg/mL after the treatment (P = 0.03), and the median concentration of pNF-H in the symptomatic neurosyphilis group decreased from baseline 1399 to 246 pg/mL after the treatment (P = 0.03). CONCLUSIONS: Neurofilament light subunit and pNF-H were significantly elevated in the symptomatic neurosyphilis patients, not in asymptomatic neurosyphilis, which was an implication of the different pathogeneses in neurosyphilis.

Expressions and clinical significance of COX-2, VEGF-C, and EFGR in endometrial carcinoma.

OBJECTIVE: The article is to study the expressions of COX-2, VEGF-C, and EGFR in endometrial carcinoma as well as its clinical significances. MATERIALS AND METHODS: Clinical data of 183 patients with endometrial carcinoma who received surgery as initial treatment in the Nanjing Drum Tower Hospital Affiliated to the Nanjing University Medical School and the Nantong Maternal and Child Health Hospital Affiliated to the Nantong University from January 2005 to December 2010 were retrospectively investigated; 152 out of the 183 patients were closely followed up. Expressions of COX-2, VEGF-C, and EGFR proteins in 152 endometrial carcinoma samples were detected by immunohistochemical S-P assay. RESULTS: A 5-year survival rate of 152 patients was 81.56% (124/152). Positive COX-2 expression rate was 67.76% (103/152), and its positive expression was related to FIGO stage, differentiation degree, and myometrial invasion depth of patients (P < 0.05), but not to lymph node metastasis (P > 0.05). Positive expression rates of VEGF-C and EGFR were 64.47% (98/152) and 82.24% (125/152), respectively, and their positive expression was associated with FIGO stage, differentiation degree, myometrial invasion depth, and lymphatic metastasis (P < 0.05). Correlation analysis on the expression of COX-2 with VEGF-C and of EGFR found that COX-2 was positively correlated with both VEGF-C and EGFR (P < 0.05, r s > 0). Patient prognosis was associated with the FIGO stage, differentiation degree, and myometrial invasion depth of tumors, as well as the presence or absence of lymph node metastasis (P < 0.05) while showing no significant association with the postoperative adjuvant therapy (P > 0.05). CONCLUSION: COX-2, VEGF-C, and EGFR are of significance for determining the FIGO stage, differentiation degree, and myometrial invasion depth of endometrial carcinoma, of which VEGF-C and EGFR are important in determining whether tumors metastasize to lymph nodes. Combined detection of COX-2, EGFR, and VEGF-C can be used as the indices for early diagnosis, recurrence prediction, and outcome evaluation for patients with endometrial carcinoma.

Effect of advanced glycation end products, extracellular matrix metalloproteinase inducer and matrix metalloproteinases on type-I collagen metabolism.

The aim of the study was to examine the association among advanced glycation end products (AGEs), extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMPs), and investigate whether AGEs affect type I collagen (COL-I) through EMMPRIN or MMPs. A co-culture system with the osteoblast-like cells (MC3T3E1) and mouse RAW264.7 cells was employed to examine the effects of AGE-bovine serum albumin (BSA) (50 mg/l), EMMPRIN antibody (5 mg/l) and AGE-BSA+EMMPRIN antibody separately on COL-I expression for 24 h. Culture media were analyzed for the content of COL-I by ELISA. The effect of different concentrations of AGE-BSA (0, 50, 100, 200 and 400 mg/l) for 24 h was assessed on COL-I levels. Finally, semiquantitative RT-PCR was used to detect the osteoblast COL-I mRNA expression and MMP-2 and MMP-9's PMAO were also measured in the culture medium. COL-I content in the culture medium decreased significantly following treatment with AGE-BSA (P<0.05). EMMPRIN antibody increased COL-I content (P<0.05). EMMPRIN antibody+AGE-BSA increased COL-I significantly (P<0.05). Different concentrations of AGE-BSA increased COL-I mRNA expression significantly compared with the control group (P<0.05), and were enhanced with increasing AGE-BSA concentration (P<0.05). Also MMP-2 and MMP-9 secretion increased significantly (P<0.05), with the increasing AGE-BSA concentration. In conclusion, an increase in AGE levels in vitro stimulates the secretion of EMMPRIN/MMPs, promotes the degradation of COL-I and reduces bone strength.

(2R,4R)-3-(tert-But-oxy-carbon-yl)-2-(3-chloro-phen-yl)-1,3-thia-zolidine-4-carb-oxy-lic acid monohydrate.

In the title compound, C(15)H(18)ClNO(4)S·H(2)O, the thia-zolidine ring displays a half-chair conformation. In the crystal, the water mol-ecules are linked to the organic acid mol-ecules via inter-molecular O-H⋯O hydrogen bonds.

Concurrent measurement of "real-world" stress and arousal in individuals with psychosis: assessing the feasibility and validity of a novel methodology.

BACKGROUND: Psychosis has been repeatedly suggested to be affected by increases in stress and arousal. However, there is a dearth of evidence supporting the temporal link between stress, arousal, and psychosis during "real-world" functioning. This paucity of evidence may stem from limitations of current research methodologies. Our aim is to the test the feasibility and validity of a novel methodology designed to measure concurrent stress and arousal in individuals with psychosis during "real-world" daily functioning. METHOD: Twenty patients with psychosis completed a 36-hour ambulatory assessment of stress and arousal. We used experience sampling method with palm computers to assess stress (10 times per day, 10 AM → 10 PM) along with concurrent ambulatory measurement of cardiac autonomic regulation using a Holter monitor. The clocks of the palm computer and Holter monitor were synchronized, allowing the temporal linking of the stress and arousal data. We used power spectral analysis to determine the parasympathetic contributions to autonomic regulation and sympathovagal balance during 5 minutes before and after each experience sample. RESULTS: Patients completed 79% of the experience samples (75% with a valid concurrent arousal data). Momentary increases in stress had inverse correlation with concurrent parasympathetic activity (ρ = -.27, P < .0001) and positive correlation with sympathovagal balance (ρ = .19, P = .0008). Stress and heart rate were not significantly related (ρ = -.05, P = .3875). CONCLUSION: The findings support the feasibility and validity of our methodology in individuals with psychosis. The methodology offers a novel way to study in high time resolution the concurrent, "real-world" interactions between stress, arousal, and psychosis. The authors discuss the methodology's potential applications and future research directions.