Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy.

Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.

Development and validation of a risk nomogram to estimate risk of hyponatremia after spinal cord injury: A retrospective single-center study.

OBJECTIVE: This study aimed to establish a nomogram-based assessment for predicting the risk of hyponatremia after spinal cord injury (SCI). DESIGN: The study is a retrospective single-center study. PARTICIPANTS: SCI patients hospitalized in the First Affiliated Hospital of Guangxi Medical University. SETTING: The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. METHODS: We performed a retrospective clinical study to collect SCI patients hospitalized in the First Affiliated Hospital of Guangxi Medical University from 2016 to 2020. Based on their clinical scores, the SCI patients were grouped as either hyponatremic or non-hyponatremic, SCI patients in 2016-2019 were identified as the training set, and patients in 2020 were identified as the test set. A nomogram was generated, the calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to validate the model. RESULTS: A total of 895 SCI patients were retrieved. After excluding patients with incomplete data, 883 patients were finally included in this study and used to construct the nomograms. The indicators used in the nomogram included sex, completeness of SCI, pneumonia, urinary tract infection, fever, constipation, white blood cell (WBC), albumin and serum Ca2+. These indices were determined by the least absolute shrinkage and selection operator (LASSO) regression analysis. The C-index of the model was 0.81, the area under the curve (AUC) of the training set was 0.82(Cl:0.79-0.85), and the validation set was 0.79(Cl:0.73-0.85). CONCLUSIONS: Nomogram has good predictive ability, sex, completeness of SCI, pneumonia, urinary tract infection, fever, constipation, WBC, albumin and serum Ca2+ were predictors of hyponatremia after SCI.

Superior hydrogen performance of in situ formed carbon modified MgH2 composites.

The MgH2-carbonic combustion product of the anthracene (CCPA) composite was synthesized by hydrogen combustion and mechanically ball-milled method to simultaneously achieve confinement by the in situ formed amorphous carbon. The amorphous carbon derived from the carbonic combustion product of anthracene in the MgH2-CCPA composite led to a significant increase in hydrogen sorption characteristics. The onset dehydrogenation temperature for the MgH2-CCPA composite was reduced to 589 K, which was 54 K less than that of pure milled MgH2. Regarding dehydrogenation kinetics, the MgH2-CCPA composite could release 5.933 wt% H2 within 3000 s at 623 K, while only 3.970 wt% H2 was liberated from the as-milled MgH2 within 3000 s at the same temperature. The MgH2-CCPA composite also exhibited excellent hydrogenation characteristics, absorbing 3.246 wt% of hydrogen within 3000 s at 423 K, which was three times higher than 0.818 wt% uptaken by the pure MgH2. The apparent activation energy (E a) for the dehydrogenation of the MgH2-CCPA composite was significantly reduced from 161.1 kJ mol-1 to 77.5 kJ mol-1. The notable improvement in sorption kinetics of the MgH2-CCPA nanocomposite is ascribed to the in situ formed amorphous carbon during the hydrogenation/dehydrogenation process.

Systematically Investigating the Pharmacological Mechanism of Momordica grosvenori in the Treatment of Spinal Cord Injury by Network Pharmacology and Experimental Verification.

Objective: This study aimed to explore the molecular mechanism of Momordica grosvenori (MG) in spinal cord injury (SCI) by network pharmacology analysis. Methods: We searched for potential active MG compounds using the TCMSP database and the BATMAN-TCM platform. The Swiss target prediction database was used to find MG-related targets and the targets of SCI from the CTD, GeneCards, and DrugBank databases. Following that, a protein-protein interaction (PPI) study was carried out. Cytoscape software was used to calculate the hub gene, and R software was used to evaluate the Gene Ontology (GO) and KEGG enrichment pathways. Finally, molecular docking between the hub protein and important compounds was performed. We verified STAT3, MAPK1, HSP90AA1, PIK3R1, PIK3CA, and RXRA potential targets by quantitative PCR. Results: We obtained 293 MG-anti-SCI targets with potential therapeutic utility by intersecting 346 MG-related targets and 7214 SCI-related targets. The top 10 identified genes, ranking in descending order of value, were SRC, STAT3, MAPK1, HSP90AA1, PIK3R1, PIK3CA, RXRA, AKT1, CREBBP, and JAK2. Through enrichment analysis and literature search, 10 signaling pathways were screened out. The molecular docking of important drugs and hub targets revealed that some had a higher binding affinity. The results of quantitative PCR indicated that MAPK1, RXRA, and STAT3 were expressed differently in in vitro experiments. Conclusion: In conclusion, the current work indicated that MG might play an anti-SCI role via multicomponent, multitarget, and multichannel interaction, which presents a novel idea for further research into the precise mechanism of MG-anti-SCI interaction.

Functional analyses of two interferon-stimulated gene 15 (ISG15) copies in large yellow croaker, Larimichthys crocea.

In this study, we conducted functional analyses for two ISG15 homologues of Larimichthys crocea (LcISG15-1 and LcISG15-2). Our results of qRT-PCR showed that both LcISG15-1 and LcISG15-2 were significantly changed in head kidney and peripheral blood, after poly (I:C) stimulation. Western blot analyses with prepared polyclonal antibodies suggested that LcISG15-1 and LcISG15-2 both could be secreted by primary head kidney lymphocytes into the extracellular milieu. The purified recombinant LcISG15-1 (rLcISG15-1) and LcISG15-2 (rLcISG15-2) could both activate primary macrophages as extracellular cytokines and significantly enhance macrophage respiratory burst, NO production and bactericidal activity and induce the expression of proinflammatory cytokine genes of the cells. Moreover, rLcISG15-2 exhibited much stronger cytokine-like activities than those of rLcISG15-1, indicating the ISG15-2 gene copy evolved enhanced activity after gene duplication of ISG15 in sciaenid fishes. These results indicated important roles of LcISG15-1 and especially LcISG15-2 in immune regulation and host immune defense of large yellow croaker against viral and bacterial infection.

Design and synthesis of novel benzimidazole-iminosugars linked a substituted phenyl group and their inhibitory activities against ß-glucosidase.

A series of novel benzimidazole-iminosugars linked a (substuituted) phenyl group on benzene ring of benzimidazole 5(a-p) and 6(a-p) have been rationally designed and conveniently synthesized through Suzuki coupling reaction in high yields. All compounds have been evaluated for their inhibitory activities against ß-glucosidase (almond). Six compounds 5d, 6d, 6e, 6i, 6n, and 6p showed more significant inhibitory activities with IC50 values in the range of 0.03-0.08 µM, almost 10-fold improved than that of the parent analogue 4, and much higher than that of the positive control castanospermine. The additional phenyl ring and the electron donating groups on it would be beneficial for the activity. Compounds 6d, 6n, and 4 had been chosen to be tested for their inhibition types against ß-glucosidase. Interestingly, three compounds have different inhibition types although they had very similar structure. Their Ki values were calculated to be 0.02 ± 0.01 µM, 0.02 ± 0.01 µM, and 0.66 ± 0.14 µM, respectively. The equilibrium dissociation constant (KD) for 6d, 6n, and 4 and ß-glucosidase was 0.04 µM, 0.03 µM and 0.45 µM by the ITC-based assay, respectively. Molecular docking work suggests that such benzimidazole-iminosugars derivatives might bind to the active site of ß-glucosidase mainly through hydrogen bonds, the additional phenyl ring towards the solvent-exposed region played an important effect on their inhibitory activity against ß-glucosidase.

[Intraoperative IPC combined with 3M warming instrument to prevent lower extremity deep venous thrombosis in patients undergoing proximal femoral anti rotation intramedullary nailing].

OBJECTIVE: To explore the effect of intermittent pneumatic compression(IPC) combined with 3M thermometer on the prevention of deep venous thrombosis(DVT) in patients with femoral intertrochanteric fracture. METHODS: From March 2016 to August 2019, 127 patients with femoral intertrochanteric fractures who underwent proximal femoral nail antirotation(PFNA) were retrospectively analyzed. They were divided into two groups according to different methods of thrombus prevention and treatment. Among them, 63 patients in group A did not use IPC and 3M thermometer;64 cases in group B were treated with IPC combined with 3M thermometer. Color Doppler ultrasound was used to dynamically monitor the DVT and changes of lower limbs during perioperative period. The venous thrombosis of lower limbs was monitored at 0, 24, 72 h and > 72 h after operation(recheck every 3 days until discharge). RESULTS: Occurrence of DVT of lower limbs after PFNA operation in two groups:there were 5 cases (7.8%) in group B and 20 cases (31.7%) in group A, there was significant difference between two groups (P=0.001). There was no significant difference in lower limb DVT between two groups at 0, 72 and > 72 h after operation(P>0.05), but the formation rate of group A was significantly higher than that of group B at 24 h after operation (P=0.049). There was no significant difference in DVT formation between group A and group B(P>0.05). However, the formation of DVT in group A was significantly higher than that in group B(P=0.012). CONCLUSION: Intraoperative IPC combined with 3M thermostat can effectively prevent DVT of lower limbs in patients undergoing PFNA surgery.

Efficacy and safety of free medial plantar flap in repair of the high-voltage electrical burns in hands.

PURPOSE: The purpose of this work was to validate the efficacy and safety of free medial plantar flap in repair of hand wounds resulted from high-voltage electrical burn. METHODS: 22 patients with high-voltage electrical burn wounds were retrieved between July 2016 and July 2018 in the Affiliated Zhengzhou Central Hospital of Zhengzhou University. All the wounds were the entrance of high-voltage electrical current. After thorough debridement, the blood vessels, nerves, tendons, joints were exposed to defects with different degrees. The soft tissue defects were repaired with the free medial plantar flap repair in 12 patients and medium-thickness skin graft in 10 patients. Postoperative management was similar between the two groups. RESULTS: All the operations were completed within 6 h. In the free medial plantar flap group, the mean follow-up period was (11.3 ± 2.4) months, ranging from 9 to 15 months, and all flaps survived; there were no vessel crises. Flaps of 10 patients healed without any complications, and local necrosis occurred in two cases, with healing after debridement. The two-point discrimination (TPD) was 7.0-11.0 mm, and the mean DASH score was 45.6 ± 7.4. In the medium-thickness skin graft group, the mean follow-up period was (10.9 ± 1.8) months. All flaps survived, and local contracture occurred in 3 cases. The TPD was 8.0-11.0 mm, and the mean DASH score was 60.7 ± 9.3. CONCLUSIONS: The free medial plantar flap is an ideal option for repairing the hand soft defects resulted from the high-voltage electrical burn.

Effects of enteral nutrition with parenteral glutamine supplementation on the immunological function in septic rats.

The aim of the present study was to investigate the effects of enteral nutrition (EN) with parenteral glutamine (GLN) supplementation on inflammatory response, lymphatic organ apoptosis, immunological function and survival in septic rats by caecal ligation and puncture (CLP). Male rats were randomly assigned into two experimental groups and two sham CLP control groups (n 10 per group). After CLP or sham CLP model and nutrition programme were completed, the GLN concentrations of plasma and tissues and several indices of immunological function including serum Ig content, circulating lymphocyte number, the CD4:CD8 ratio, the neutrophil phagocytosis index (NPI), the organ index and apoptosis of thymus and spleen, and plasma cytokine levels were determined. Moreover, the survival in septic rats was observed. The results revealed that EN with parenteral GLN supplementation remarkably increased the GLN concentrations of plasma and tissues, serum Ig content, the circulating lymphocyte number, the CD4:CD8 ratio, the indexes of thymus and spleen, NPI and survival compared with the control group (P< 0·05). In contrast, the apoptosis of thymus and spleen and the levels of TNF-α, IL-1ß and IL-6 in plasma were obviously decreased compared with the control group (P< 0·05). These results show that EN with parenteral GLN supplementation diminished the release of inflammatory cytokines, attenuated lymphatic organ apoptosis, enhanced the immunological function and improved survival in septic rats.

[Comparative study of four alkaloids contents and antitussive activities of Stemona tuberosa from different habitats of Guangxi Province].

OBJECTIVE: To compare the contents of four alkaloids and antitussive activities of Stemona tuberosa from different habitats of Guangxi Province. METHODS: The HPLC separation was performed on a Merck Purospher STAR RP18 (250 mm x 4. 6 mm, 5 µm) column by gradient elution using 0. 05% ammonia-acetonitrile as the mobile phase. The flow rate was 1. 0 mL/min, the dectection wave-length was set at 210 nm,and the column temperature was 40 °C. The antitussive potency of total alkaloids of Stemonae Radix from different habitats was evaluated on guinea pigs with citric acid aerosol to induce cough. RESULTS: The range of recoveries of this mehtod was 98. 24% ~ 101. 21%, with all the constituents showing good linearity(the correlation coefficents above 0. 999). The major chemotype of Stemonae Radix in Guangxi was stemoninine, following by tuberostemonine and croomine, and finally neotuberostemonine. The antitussive activitiy of Stemona tuberosa was in a concentration-dependent manner. CONCLUSION: Stemonae Radix from Dongxing, Fangcheng can reduce cough times and prolong cough incubation period, and thus Dongxing, Fangcheng is the best habitat in Guangxi in the present experiments.