Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

OBJECTIVES: To develop a heterogeneous graph prediction method based on the fusion of multi-layer semantics and topological information for addressing the challenges in drug-target interaction prediction, including insufficient modeling of high-order semantic dependencies, lack of adaptive fusion of semantic paths, and over-smoothing of node features. METHODS: A heterogeneous graph network with multiple types of entities such as drugs, proteins, side effects, and diseases was constructed, and graph embedding techniques were used to obtain low-dimensional feature representations. An adaptive metapath search module was introduced to automatically discover semantic path combinations for guiding the propagation of high-order semantic information. A semantic aggregation mechanism integrating multi-head attention was designed to automatically learn the importance of each semantic path based on contextual information and achieve differentiated aggregation and dynamic fusion among paths. A structure-aware gated graph convolutional module was then incorporated to regulate the feature propagation intensity for suppressing redundant information and redcuing over-smoothing. Finally, the potential interactions between drugs and targets were predicted through an inner product operation. RESULTS: Compared with existing drug-target interaction prediction methods, the proposed method achieved an average improvement of 3.4% and 2.4%, 3.0% and 3.8% in terms of the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC) on public datasets, respectively. CONCLUSIONS The drug-target interaction prediction method developed in this study can effectively extract complex high-order semantic and topological information from heterogeneous biological networks, thereby improving the accuracy and stability of drug-target interaction prediction. This method provides technical support and theoretical foundation for precise drug target discovery and targeted treatment of complex diseases.
Semantics ; Humans ; Drug Interactions ; Neural Networks, Computer ; Algorithms

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems faced by bus drivers and should receive special attention. Objective To explore the associations of weekly working hours and sleep quality with neck and lower back WMSDs among bus drivers, as well as assess the potential mediating role of sleep quality. Methods From June to December 2022, we recruited bus drivers from 5 subsidiaries of the Shenzhen Bus Group by convenient sampling method. Demographic characteristics, lifestyles, and work-related features of the bus drivers were collected through a questionnaire survey. The Pittsburgh Sleep Quality Index (PSQI) scale and the Musculoskeletal Disorders Survey Questionnaire were used to assess sleep quality and WMSDs respectively. Logistic regression models were applied to analyze the associations of weekly working hours and sleep quality with WMSDs in neck and lower back. Furthermore, mediation analysis was performed to investigate the role of sleep quality in the associations between weekly work hours and neck and lower back WMSDs. Results A total of 1792 valid questionnaires were collected, with a response rate of 95.07%. Among these, 89.3% of the bus drivers worked more than 40 h per week, and the positive rate of poor sleep quality was 28.2%. The overall positive rate of WMSDs within one year before the survey was 69.12%. Among different body regions, the leading positive rates were identified in neck and lower back regions, at 55.92% and 53.68%, respectively. The logistic regression model showed that compared to the bus drivers with weekly work hours ≤40 h, those weekly worked (40~48] h (OR=1.43, 95%CI: 1.02, 2.01; OR=1.65, 95%CI: 1.17, 2.34), (48~56] h (OR=2.69, 95%CI: 1.89, 3.83; OR=2.30, 95%CI: 1.62, 3.29) and ＞56 h (OR=2.63, 95%CI: 1.86, 3.74; OR=3.23, 95%CI: 2.27, 4.62) had significantly increased risk of WMSDs in neck and lower back. Additionally, when compared to those with good sleep quality, bus drivers with poor sleep quality had higher risks of both neck and lower back WMSDs (OR=4.08, 95%CI: 3.20, 5.23; OR=4.15, 95%CI: 3.26, 5.30, respectively). Further mediation analysis indicated that sleep quality partially mediated the associations between weekly working hours and both neck and lower back WMSDs, with 36.15% and 33.68% as the respective proportion of mediation. Conclusion The positive rate of WMSDs is high among bus drivers, and the most common WMSDs occur in neck and lower back. Long working hours and poor sleep quality are significantly associated with increased risks of neck and lower back WMSDs. Sleep quality may mediate the associations of weekly working hours with neck and lower back WMSDs.

Objective:To explore the efficacy and safety of camrelizumab combined with chemotherapy in treatment of advanced esophageal carcinoma.Methods:A retrospective cohort study was conducted. A total of 84 patients with advanced esophageal carcinoma admitted to the First Affiliated Hospital of Xi'an Medical University from June 2020 to May 2022 were selected, and all patients were divided into the observation group and the control group according to the different treatment methods, 42 cases in each group. The control group was given albumin-bound paclitaxel combined with cisplatin chemotherapy, and the observation group was given camrelizumab based on the control group. The clinical efficacy, survival, tumor markers levels, T lymphocyte subsets levels, quality of life and adverse reactions were compared in both groups.Results:There were no statistically significant differences in age, gender, body mass index, clinical stage and tumor site between the 2 groups (all P > 0.05). There were 9 cases of partial remission (PR), 15 cases of stable disease (SD) and 18 cases of progression of the disease (PD) in the control group; and 15 cases of PR, 18 cases of SD, 9 cases of PD in the observation group. There was no statistically significant difference in objective remission rate between the control group and observation group [21.4% (9/42) vs. 35.7% (15/42), χ2 = 2.10, P = 0.147]. The disease control rate in the observation group was higher than that in the control group [78.6% (33/42) vs. 57.1% (24/42)], and the difference was statistically significant ( χ2 = 4.42, P = 0.035). The median overall survival time was 12 months (95% CI: 10.7-13.3 months) and 9 months (95% CI: 7.6-10.4 months), respectively in the observation group and the control group, and the difference in overall survival was statistically significant ( χ2 = 9.45, P = 0.002). The levels of carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) in both groups after treatment were lower than those before treatment, and the levels of these tumor markers in the observation group [CA125: (54±6) IU/ml, CEA: (9.2±1.1) μg/L, SCC: (0.72±0.19) μg/L] were lower than those in the control group [CA125: (61±7) IU/ml, CEA: (11.3±1.5) μg/L, SCC: (1.26±0.30) μg/L] (all P < 0.001). After treatment, the T lymphocyte proportions of CD3 +, CD4 + and the level of CD4 +/CD8 + in the observation group were higher than those before treatment; and T lymphocyte proportions of CD3 +, CD4 + and the level of CD4 +/CD8 + in the observation group were higher than those in the control group (all P < 0.05). The scores of quality of life scale in both groups after treatment were higher than those before treatment (all P < 0.001), and the score in the observation group was higher than that in the control group [(64±5) points vs. (60±4) points], and the difference was statistically significant ( t = 4.05, P < 0.001). There were no statistically significant differences in the incidence of gastrointestinal reactions, liver dysfunction and rash between the 2 groups (all P > 0.05). The incidence of cutaneouscapillary endothelial proliferation in the observation group was higher than that in the control group [14.29% (6/42) vs. 0 (0/42) ], and the difference was statistically significant ( P = 0.026). Conclusions:Camrelizumab combined with chemotherapy can improve the disease condition, prolong the survival time, improve the quality of life and regulate the disorder of T lymphocytes in patients with advanced esophageal carcinoma, and its safety is controllable.

Objective:To explore the efficacy and safety of camrelizumab combined with chemotherapy in treatment of advanced esophageal carcinoma.Methods:A retrospective cohort study was conducted. A total of 84 patients with advanced esophageal carcinoma admitted to the First Affiliated Hospital of Xi'an Medical University from June 2020 to May 2022 were selected, and all patients were divided into the observation group and the control group according to the different treatment methods, 42 cases in each group. The control group was given albumin-bound paclitaxel combined with cisplatin chemotherapy, and the observation group was given camrelizumab based on the control group. The clinical efficacy, survival, tumor markers levels, T lymphocyte subsets levels, quality of life and adverse reactions were compared in both groups.Results:There were no statistically significant differences in age, gender, body mass index, clinical stage and tumor site between the 2 groups (all P > 0.05). There were 9 cases of partial remission (PR), 15 cases of stable disease (SD) and 18 cases of progression of the disease (PD) in the control group; and 15 cases of PR, 18 cases of SD, 9 cases of PD in the observation group. There was no statistically significant difference in objective remission rate between the control group and observation group [21.4% (9/42) vs. 35.7% (15/42), χ2 = 2.10, P = 0.147]. The disease control rate in the observation group was higher than that in the control group [78.6% (33/42) vs. 57.1% (24/42)], and the difference was statistically significant ( χ2 = 4.42, P = 0.035). The median overall survival time was 12 months (95% CI: 10.7-13.3 months) and 9 months (95% CI: 7.6-10.4 months), respectively in the observation group and the control group, and the difference in overall survival was statistically significant ( χ2 = 9.45, P = 0.002). The levels of carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) in both groups after treatment were lower than those before treatment, and the levels of these tumor markers in the observation group [CA125: (54±6) IU/ml, CEA: (9.2±1.1) μg/L, SCC: (0.72±0.19) μg/L] were lower than those in the control group [CA125: (61±7) IU/ml, CEA: (11.3±1.5) μg/L, SCC: (1.26±0.30) μg/L] (all P < 0.001). After treatment, the T lymphocyte proportions of CD3 +, CD4 + and the level of CD4 +/CD8 + in the observation group were higher than those before treatment; and T lymphocyte proportions of CD3 +, CD4 + and the level of CD4 +/CD8 + in the observation group were higher than those in the control group (all P < 0.05). The scores of quality of life scale in both groups after treatment were higher than those before treatment (all P < 0.001), and the score in the observation group was higher than that in the control group [(64±5) points vs. (60±4) points], and the difference was statistically significant ( t = 4.05, P < 0.001). There were no statistically significant differences in the incidence of gastrointestinal reactions, liver dysfunction and rash between the 2 groups (all P > 0.05). The incidence of cutaneouscapillary endothelial proliferation in the observation group was higher than that in the control group [14.29% (6/42) vs. 0 (0/42) ], and the difference was statistically significant ( P = 0.026). Conclusions:Camrelizumab combined with chemotherapy can improve the disease condition, prolong the survival time, improve the quality of life and regulate the disorder of T lymphocytes in patients with advanced esophageal carcinoma, and its safety is controllable.

Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P＜0.001),while MAP was not significantly correlated with gestational week(P＞0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.

AIM:To investigate the effects of the γ-aminobutyric acid(GABAergic)neural pathway from the anterior cingulate cortex(ACC)to the nucleus accumbens(NAc)on the regulation of irritable bowel syndrome(IBS)and its underlying mechanisms in mice.METHODS:(1)A C57BL/6J mice model of IBS was established by using chronic acute combing stress(CACS).The mice were divided into a normal group and an IBS group(n=8).The presence of IBS-like symptoms was determined through behavioural tests,an intestinal motility test and abdominal withdrawal reflex scores.(2)Fluorescence gold(FG)retrograde tracing and immunohistochemistry were used to investigate the ACC-NAc GABAergic neural pathway and to examine the activation of GABA in the ACC in IBS mice(n=8).(3)A total of 1.5 μL of normal saline(NS),GABAA receptor antagonist bicuculline(BIC)or agonist isoguvacine hydrochloride(Isog)was ad-ministered via a preburied catheter into the NAc of mice in IBS and normal groups.The mice were randomly divided into three groups(n=8):NS group,BIC group and Isog group.IBS-like symptoms were assessed.(4)The mice were prein-jected with AAV2/9-mDlx-iCre-WPRE-pA in the ACC and AAV2/2Retro Plus-hSyn-DIO-hM3D(Gq)-eGFP-WPRE-pA in the NAc and subsequently divided into four groups(n=8):NS(intraperitoneal injection)+NS(NAc microinjection)group,NS+BIC group,clozapine N-oxide(CNO)+NS group and CNO+BIC group.The mice who received AAV2/2Retro-hSyn-DIO-hM4D(Gi)-EGFP-WPRE-pA in the NAc were randomly divided into three groups(n=8):NS+NS group,NS+BIC group and CNO+NS group.Enzyme-linked immunosorbent assay(ELISA)was employed to estimate the expression levels of histamine and 5-hydroxytryptamine(5-HT)in colon tissue,and the effects of GABAergic neural pathways from ACC to NAc on IBS were studied.RESULTS:CACS induced IBS-like symptoms in mice.The results of FG retrograde tracing combined with fluorescence immunohistochemistry showed that GABA neurons of ACC could project to NAc.The injection of BIC in the NAc was found to significantly reduce anxiety-like behaviours,diarrheal symptoms and visceral hy-persensitivity in the IBS mice(P<0.05).Chemogenetic inhibition of the ACC-NAc GABAergic neurons ameliorated IBS-like symptoms in mice(P<0.05).CONCLUSION:The GABAergic pathway of ACC-NAc might be involved in the regu-lation of IBS in mice,which may be related to the release of histamine and 5-HT in colon tissue.

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses. Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann-Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes. Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy. Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

Objective:To develop and test the intelligent model for automatically counting the number of vertebral ossification centers below the end of conus medullaris.Methods:From January 2021 to October 2022, 3 000 ultrasound images of the sacrococcygeal spinal middle sagittal plane were retrospectively selected from Shenzhen Maternal and Child Healthcare Hospital and Zhuhai People′s Hospital. The vertebral ossification center and spinal conus medullaris were artificially fine-marked in 2, 800 images for segmentation training. Yolov8 algorithm was used to build the segmentation model for segmentation training, and the fitting and automatic counting of vertebral ossification centers were carried out by post-processing. In the other 200 planes, the counting was performed by the artificial intelligence (AI) model, attending physician (D1), and junior physician (D2), and the accuracy of their performance were evaluated by a specialist physician. The accuracy and the time spent between D1, D2, and AI were compared.Results:The accuracy of AI model segmentation fitting and counting reached 95.00% (190/200) by the specialist physician evaluation, which was almost equal to 94.50%(189/200) by D1( P=0.823) and higher than that of 88.50% by D2(177/200)( P=0.012). The counting time spent for D1, D2, and AI model were 5.00 (4.25, 6.00)s, 7.00 (7.00, 8.00)s, 0.09 (0.08, 0.10)s, respectively, showing that the time spent by AI model was significantly shorter than that of doctors(all P<0.001). Conclusions:The trained artificial intelligence model can efficiently and accurately complete the vertebral ossification center counting below the end of conus medullaris, equivalent to the level of attending physicians. This study is expected to be further applied in the screening of fetal spina bifida and improve the automation and intelligence level of prenatal ultrasound screening.

The paper summarizes the imaging evaluation methods for assessing the degree of carotid artery stenosis and analyzes the unique advantages and limitations of various imaging techniques in vascular imaging based on existing guidelines and consensus.The paper focuses on reviewing the clinical applications of several novel ultrasound technologies,including the use of advanced hemodynamic parameters such as blood flow dispersion(Tur index)and wall shear stress(WSS).Carotid artery stenosis is closely associated with cardiovascular disease.Although non-invasive and radiation-free ultrasound technology has certain limitations in diagnostic accuracy to a certain extent,with the continuous emergence of advanced functions such as ultrasound hemodynamics and vascular elasticity,the combination of multi-modality and multi-parameter ultrasound is expected to become an important method for efficient diagnosis of arterial stenosis in the future.