Heavy metals and metalloids exposure and liver function in Chinese adults - A nationally representative cross-sectional study.

BACKGROUND: In China, the effects of heavy metals and metalloids (HMMs) on liver health are not consistently documented, despite their prevalent environmental presence. OBJECTIVE: Our research assessed the association between HMMs and liver function biomarkers in a comprehensive sample of Chinese adults. METHODS: We analyzed data from 9445 participants in the China National Human Biomonitoring survey. Blood and urine were evaluated for HMM concentrations, and liver health was gauged using serum albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) metrics. Various statistical methods were employed to understand the relationship between 11 HMMs and liver function, adjusting for multiple factors. We also explored interactions with alcohol intake, gender, and age. RESULTS: Among HMMs, selenium in blood [weighted geometric mean (GM) = 95.56 µg/L] and molybdenum in urine (GM = 46.44 µg/L) showed the highest concentrations, while lead in blood (GM = 21.92 µg/L) and arsenic in urine (GM = 19.80 µg/L) had the highest levels among risk HMMs. Manganese and thallium consistently indicated potential risk factor to liver in both sample types, while selenium displayed potential liver protection. Blood HMM mixtures were negatively associated with ALB (ß = -0.614, 95% CI: -0.809, -0.418) and positively with AST (ß = 0.701, 95% CI: 0.290, 1.111). No significant associations were found in urine HMM mixtures. Manganese, tin, nickel, and selenium were notable in blood mixture associations, with selenium and cobalt being significant in urine. The relationship of certain HMMs varied based on alcohol consumption. CONCLUSION: This research highlights the complex relationship between HMM exposure and liver health in Chinese adults, particularly emphasizing metals like manganese, thallium, and selenium. The results suggest a need for public health attention to low dose HMM exposure and underscore the potential benefits of selenium for liver health. Further studies are essential to establish causality.

Novel hKDR mouse model depicts the antiangiogenesis and apoptosis-promoting effects of neutralizing antibodies targeting vascular endothelial growth factor receptor 2.

Vascular endothelial growth factor receptor 2 (VEGFR2)/KDR plays a critical role in tumor growth, diffusion, and invasion. The amino acid sequence homology of KDR between mouse and human in the VEGF ligand-binding domain was low, thus the WT mice could not be used to evaluate Abs against human KDR, and the lack of a suitable mouse model hindered both basic research and drug developments. Using the CRISPR/Cas9 technique, we successfully inserted different fragments of the human KDR coding sequence into the chromosomal mouse Kdr exon 4 locus to obtain an hKDR humanized mouse that can be used to evaluate the marketed Ab ramucirumab. In addition, the humanized mAb VEGFR-HK19 was developed, and a series of comparative assays with ramucirumab as the benchmark revealed that VEGFR-HK19 has higher affinity and superior antiproliferation activity. Moreover, VEGFR-HK19 selectively inhibited tumor growth in the hKDR mouse model but not in WT mice. The most important binding epitopes of VEGFR2-HK19 are D257, L313, and T315, located in the VEGF binding region. Therefore, the VEGFR2-HK19 Ab inhibits tumor growth by blocking VEGF-induced angiogenesis, inflammation, and promoting apoptosis. To our best knowledge, this novel humanized KDR mouse fills the gaps both in an animal model and the suitable in vivo evaluation method for developing antiangiogenesis therapies in the future, and the newly established humanized Ab is expected to be a drug candidate possibly benefitting tumor patients.

Family functioning and health-related quality of life of inpatients with coronary heart disease: a cross-sectional study in Lanzhou city, China.

BACKGROUND: A key outcome in coronary heart disease (CHD) is Health Related Quality of Life (HRQoL), and family functioning is important in the management of CHD. But few studies have examined both together, and little is known about them among inpatients with CHD in less developed areas of China. Therefore, this study aimed to assess the HRQoL and family functioning status of inpatients with CHD in Lanzhou from Northwest China, and identify the factors that affect their HRQoL. METHODS: A cross­sectional study was conducted in 224 CHD inpatients at one major hospital. Sociodemographic data and disease information of CHD inpatients were collected by face-to-face using a structured questionnaire and data were also obtained from patient medical records. HRQoL was measured using the Sickness Impact Profile (SIP). Family functioning was measured using the family APGAR index. Multiple binary logistic regression analysis (MBLRA) was used to explore potential risk factors associated with HRQoL, and Pearson's correlations were used to assess the relationship between family functioning and HRQoL. RESULTS: The overall, physical and psychosocial SIP scores were 25.03 ± 8.52, 18.61 ± 9.90 and 28.08 ± 9.64, respectively. The total family APGAR score was 6.11 ± 2.45. MBLRA found older age, poorer cardiac function and more severe disease were associated with poorer HRQoL, while better family functioning, higher monthly income, and urban living were associated with better HRQoL. Family functioning was weakly to moderately correlated with total and psychosocial HRQoL. CONCLUSIONS: Older and less affluent inpatients with lower educational level, less family support and more severe CHD have poorest quality of life, and health care providers should consider interventions to support them.

The influence of professional identity on work engagement among nurses working in nursing homes in China.

AIM: To assess the influence of professional identity on work engagement among nurses working in nursing homes in China. BACKGROUND: China is faced with an increasingly ageing population. There is a shortage of adequately trained nursing personnel and a high turnover rate among nurses. Work engagement is a key factor in improving nurses' performance and improving professional identity is critical to increase work productivity and satisfaction. METHODS: We conducted a cross-sectional survey of 272 nurses working in nursing homes. And the data were analysed by descriptive analyses, univariate analysis and Multiple regression analyses. RESULTS: The overall average work engagement score was 3.99 ± 1.04. Professional identity was the only factor that significantly influenced the 'vigour' and 'absorption' of nurses. Age, ethnicity and professional identity were significant predictors of 'dedication'. CONCLUSIONS: A positive professional identity can lead to a better work engagement among nurses working in nursing homes in China. IMPLICATIONS FOR NURSING MANAGEMENT: To enhance the work engagement of nurses working in nursing homes, nursing leaders should create a respectful and equal work environment, create a favourable image of the industry and the profession and strengthen training to improve the professional identity.

Generation of a uniform thymic malignant lymphoma model with C57BL/6J p53 gene deficient mice.

Lymphoma is the third most common cancer diagnosed in children, and T-cell lymphoma has the worst prognosis based on clinical observations. To date, a lymphoma model with uniform penetrance has not yet been developed. In this study, we generated a p53 deficient mouse model by targeting embryonic stem cells derived from a C57BL/6J mouse strain. Homozygous p53 deficient mice exhibited a higher rate of spontaneous tumorigenesis, with a high spontaneous occurrence rate (93.3%) of malignant lymphoma. Because tumor models with high phenotypic consistency are currently needed, we generated a lymphoma model by a single intraperitoneal injection of 37.5 or 75 mg/kg N-methyl-N-nitrosourea to p53 deficient mice. Lymphoma and retinal degeneration occurred in 100% of p53 +/- mice administered with higher concentrations of N-methyl-N-nitrosourea, a much greater response than those of previously reported models. The main anatomic sites of lymphoma were the thymus, spleen, bone marrow, and lymph nodes. Both induced and spontaneous lymphomas in the thymus and spleen stained positive for CD3 antigen, and flow cytometry detected positive CD4 and/or CD8 cells. Based on our observations and previous data, we hypothesize that mice with a B6 background are prone to lymphomagenesis.

Neural tube defects: role of lithium carbonate exposure in embryonic neural development in a murine model.

BACKGROUND: Lithium carbonate (Li2CO3) is widely used in the treatment of clinical-affective psychosis. Exposure to Li2CO3 during pregnancy increases the risk of neural tube defects (NTDs) in offspring, which are severe birth defects of the central nervous system. The mechanism of Li2CO3-induced NTDs remains unclear. METHODS: C57BL/6 mice were injected with different doses of Li2CO3 intraperitoneally on gestational day 7.5 (GD7.5), and embryos collected at GD11.5 and GD13.5. The mechanisms of Li2CO3 exposure-induced NTDs were determined utilizing immunohistochemistry, western blotting, EdU imaging, enzymatic method, gas chromatography-mass spectrometry (GC-MS), ELISA and HE staining. RESULTS: The NTDs incidence was 33.7% following Li2CO3 exposure. Neuroepithelial cell proliferation and phosphohistone H3 level were significantly increased in NTDs embryos, compared with control group (P < 0.01), while the expressing levels of p53 and caspase-3 were significantly decreased. IMPase and GSK-3ß activity was inhibited in Li2CO3-treated maternal and embryonic neural tissues (P < 0.01 and P < 0.05, respectively), along with decreased levels of inositol and metabolites, compared with control groups (P < 0.01). CONCLUSIONS: Lithium-induced NTDs model in C57BL/6 mice was established. Enhanced cell proliferation and decreased apoptosis following lithium exposure were closely associated with the impairment of inositol biosynthesis, which may contribute to lithium-induced NTDs. IMPACT: Impairment of inositol biosynthesis has an important role in lithium exposure-induced NTDs in mice model. Lithium-induced NTDs model on C57BL/6 mice was established. Based on this NTDs model, lithium-induced impairment of inositol biosynthesis resulted in the imbalance between cell proliferation and apoptosis, which may contribute to lithium-induced NTDs. Providing evidence to further understand the molecular mechanisms of lithium-induced NTDs and enhancing its primary prevention.

The Neuroprotective Mechanism of Spinal Cord Stimulation in Spinal Cord Ischemia/Reperfusion Injury.

BACKGROUND: Spinal cord ischemia/reperfusion (I/R) injury following thoracoabdominal aneurysm surgery can lead to severe lower limb neurologic defect. The preliminary result of our study suggested that spinal cord stimulation (SCS) postconditioning effectively protected spinal cord from I/R injury on rabbits. But the mechanism is unknown. In this study, we further investigated the mechanism of SCS postconditioning. METHOD: New Zealand white rabbits were randomly divided into sham, I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group (n = 24/group). Transient spinal cord ischemia was induced by infrarenal aortic balloon occlusion and performed on all rabbits except rabbits of sham group. Rabbits of I/R group received no further intervention. Rabbits of I/R + 2 Hz SCS and I/R + 50 Hz SCS group received 2 Hz or 50 Hz SCS for 30 min at the onset of reperfusion and then daily. The expression of Akt (serine-threonine kinase)/p-Akt, STAT3 (signal transducer and activator of transcription 3)/p-STAT3 and GSK-3ß (glycogen synthase kinase)/p-GSK-3ß of spinal cord were measured by Western blot analysis at 8 h, 1 day, 3 day, and 7 day of reperfusion. RESULT: The Akt expressions of sham, I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group were not significantly different at all prescribed time points, while the p-Akt expression of I/R + 2 Hz SCS group was significantly higher than that of I/R group and sham group at all prescribed time points; The STAT3 and p-STAT3 expression of I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group were not significantly different at all prescribed time points except that at 1day of reperfusion the p-STAT3 expression of I/R + 50 Hz SCS group was significantly lower than I/R group. The GSK-3ß and p-GSK-3ß expressions of I/R, I/R + 2 Hz SCS and I/R + 50 Hz SCS group were not significantly different at all prescribed time points. CONCLUSION: The neuroprotective effect of 2 Hz SCS postconditioning in spinal cord I/R injury is related to Akt activation but not regulation of STAT3 and GSK-3ß phosphorylation.

Solvent-Free Secondary Growth of Highly b-Oriented MFI Zeolite Films from Anhydrous Synthetic Powder.

Up to date, zeolite films have been mainly fabricated by in situ crystallization, secondary growth in a solution/hydrogel, or occasionally by vapor phase transformation of dry gel. Here we demonstrate for the first time a solvent-free secondary growth method for b-oriented silica MFI zeolite films using the synthetic powder from ground anhydrous raw solids in the presence of NH4F. Typically, precisely b-oriented MFI zeolite films are synthesized from seed layers of highly b-oriented MFI zeolite crystals in the synthetic powder of 1SiO2:0.035TPABr:0.05NH4F at 175 °C for 6 h. If needed, b-oriented MFI zeolite multilayer films can be acquired by changing the synthesis time or the amount of NH4F in the synthetic powder. Compared with the traditional hydrothermal synthesis, the approach developed here may provide a new avenue for fabricating high quality zeolite films/membranes.

Improvements on biological and antimicrobial properties of titanium modified by AgNPs-loaded chitosan-heparin polyelectrolyte multilayers.

Microbial infection around dental implants is a major cause for the loss of devices, including soft tissue infection in early period, post-operation peri-implantitis, and osseointegration failure. Silver nanoparticles (AgNPs) with wide antimicrobial spectrum, strong antimicrobial effect and hypotoxicity, as well as low incidence of antibiotic resistance, are widely involved in biomedical applications. Herein, firmly anchoring AgNPs onto the surface of implants through physical-chemical reaction is likely to relieve the above issues. In this study, AgNPs were biosynthesized by a simple and "green" method with chitosan (CS) as stabilizing and reducing agents. Then, AgNPs-loaded CS-heparin polyelectrolyte multilayers (PEMs) were constructed on alkali-heat treated titanium (Ti) substrates via layer-by-layer (LbL) self-assembly technique. The successful surface modification could be confirmed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), and the constructed system could provide the continuous release of Ag+ over 28 days till mucosa healing. In short, this work revealed that the construction of multilayer coatings containing AgNPs on Ti substrates promoted adhesion and proliferation of human gingival fibroblasts (HGFs) and also enhanced the antimicrobial properties. This manifests the LbL technique is a viable and promising method for forming continuous antimicrobial coatings, to reduce microbial infection and improve the quality of peri-implant soft tissue seal. The preparation process of AgNPs-loaded CS-heparin PEMs on Ti substrate.

Low-level laser irradiation modulates the proliferation and the osteogenic differentiation of bone marrow mesenchymal stem cells under healthy and inflammatory condition.

The aim of this in vitro study was to evaluate the effects of low-level laser therapy (LLLT) at different energy intensities on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under healthy and inflammatory microenvironments. Human BMSCs and BMSCs from inflammatory conditions (i-BMSCs, BMSCs treated with tumor necrosis factor α; TNF-α) were subject to LLLT (Nd:YAG;1064 nm) at different intensities. We designed one control group (without irradiation) and four testing groups (irradiation at 2, 4, 8, and 16 J/cm2) for both BMSCs and i-BMSCs. Cell proliferation was measured using colony-forming unit fibroblast assay and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Osteogenic capacity of cells was determined by alkaline phosphatase (ALP) staining, ALP activity assay, Alizarin Red S staining and the mRNA transcript levels of genes runt-related transcription factor 2 (Runx2), ALP, and osteocalcin. Moreover, the effects of LLLT on secretion of TNF-α in BMSCs and i-BMSCs were measured by enzyme-linked immunosorbent assay. Our results demonstrated LLLT could significantly promote BMSC proliferation and osteogenesis at densities of 2 and 4 J/cm2. LLLT at density of 8 J/cm2 could promote the proliferation and osteogenesis of i-BMSCs. However, LLLT at 16 J/cm2 significantly suppressed the proliferation and osteogenesis of BMSCs both in healthy and in inflammatory microenvironment. Moreover, we also found that the expression of TNF-α was obviously inhibited by LLLT at 4, 8, and 16 J/cm2, in an inflammatory microenvironment. Considering these findings, LLLT could improve current in vitro methods of differentiating BMSCs under healthy and inflammatory microenvironments prior to transplantation.

A case report of spontaneous staphylococcal meningitis in a cynomolgus monkey.

This report describes a suppurative meningitis in a young cynomolgus. The animal had neutrophil aggregation in the subarachnoid space and hemorrhage in bilateral adrenal glands. Staphylococcus was identified by FISH in brain. To our knowledge, this is the first case of staphylococcal meningitis with Waterhouse-Friderichsen syndrome in a cynomolgus monkey.

A safety and immunogenicity study of a novel subunit plague vaccine in cynomolgus macaques.

Plague has led to millions of deaths in history and outbreaks continue to the present day. The efficacy limitations and safety concerns of the existing killed whole cell and live-attenuated vaccines call for the development of new vaccines. In this study, we evaluated the immunogenicity and safety of a novel subunit plague vaccine, comprising native F1 antigen and recombinant V antigen. The cynomolgus macaques in low- and high-dose vaccine groups were vaccinated at weeks 0, 2, 4 and 6, at dose levels of 15 µg F1 + 15 µg rV and 30 µg F1 + 30 µg rV respectively. Specific antibodies and interferon-γ and interleukin-2 expression in lymphocytes were measured. For safety, except for the general toxicity and local irritation, we made a systematic immunotoxicity study on the vaccine including immunostimulation, autoimmunity and anaphylactic reaction. The vaccine induced high levels of serum anti-F1 and anti-rV antibodies, and caused small increases of interferon-γ and interleukin-2 in monkeys. The vaccination led to a reversible increase in the number of peripheral blood eosinophils, the increases in serum IgE level in a few animals and histopathological change of granulomas at injection sites. The vaccine had no impact on general conditions, most clinical pathology parameters, percentages of T-cell subsets, organ weights and gross pathology of treated monkeys and had passable local tolerance. The F1 + rV subunit plague vaccine can induce very strong humoral immunity and low level of cellular immunity in cynomolgus macaques and has a good safety profile.

[Analysis of creatinine in human urine by isotope dilution high performance liquid chromatography/tandem mass spectrometry].

OBJECTIVE: To develop a method for determination of creatinine in human urine by isotope dilution high performance liquid chromatography/tandem mass spectrometry. METHODS: The urine samples were directly diluted 800 fold by mixed solution of methanol and water( 7 ∶ 3, V/V), and filtered with 0. 45 µm filter. The chromatographic separation was carried on an Atlantis Hilic Silica column( 2. 1 mm × 150 mm, 3 µm). Methanol and water mixture solution( 7 ∶ 3, V/V) were used as the mobile phases in an isocratic gradient. Mass detection was then conducted by electrospray ionization in positive ion( ESI+) mode and multiple reaction monitoring( MRM) mode. The concentration of creatinine was quantified by stable isotope labelled d3-creatinine internal standard. Standard reference material of urine creatinine was used to evaluate the accuracy of method, and then the uncertainty of this detection method was also evaluated. RESULTS: The calibration curve of creatinine showed a good linear relationship in the range of 0. 31 µg/mL to 5. 00 µg/mL, and the related coefficient was 0. 999 9. The limit of detection( LOD) and limit of quantitation( LOQ) were 0. 003 mg/mL and 0. 011 mg/mL respectively, in real urine. Recoveries rates at two levels were 93. 9%-104. 0% and 90. 6%-93. 8%, with the relative standard deviation of 4. 4%-7. 6% and 4. 6%-7. 8%( n = 6), respectively. The creatinine concentration of standard reference material was in accordance with the reference value. The measurement uncertainty was mainly due to standard curves, recoveries rates and permissible error of instrument. CONCLUSION: The determination method is successfully applied to measure the concentration of creatinine in human urine with efficiency, accuracy and high sensitivity.

Endogenous controls of gene expression in N-methyl-N-nitrosourea-induced T-cell lymphoma in p53-deficient mice.

BACKGROUND: Real-time polymerase chain reaction (PCR) has become an increasingly important technique for gene expression profiling because it can provide insights into complex biological and pathological processes and be used to predict disease or treatment outcomes. Although normalized data are necessary for an accurate estimation of mRNA expression levels, several pieces of evidence suggest that the expression of so-called housekeeping genes is not stable. This study aimed to validate reference genes for the normalization of real-time PCR in an N-methyl-N-nitrosourea (MNU)-induced T-cell lymphoma mouse model. METHODS: T-cell lymphomas were generated in p53-deficient mice by treatment with 37.5 mg/kg MNU. Thymus and spleen were identified as the primary target organs with the highest incidences of lymphomas. We analyzed the RNA expression levels of eight potential endogenous reference genes (Gapdh, Rn18s, Actb, Hprt, B2M, Rplp0, Gusb, Ctbp1). The expression stabilities of these reference genes were tested at different time points after MNU treatment using geNorm and NormFinder algorithms. RESULTS: A total of 65% of MNU-treated mice developed T-cell lymphomas, with the spleen and thymus as the major target organs. All candidate reference genes were amplified efficiently by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Gene stability evaluation after MNU treatment and during lymphomagenesis revealed that Ctbp1 and Rplp0 were the most stably expressed genes in the thymus and spleen, respectively. RT-PCR of thymus RNA using two additional sets of primer confirmed that Ctbp1 was the most stable of all the candidate reference genes. CONCLUSIONS: We provided suitable endogenous controls for gene expression studies in the T-cell lymphoma model.

Effect of azithromycin in combination with simvastatin in the treatment of chronic obstructive pulmonary disease complicated by pulmonary arterial hypertension.

OBJECTIVE: To evaluate the effect of azithromycin in combination with simvastatin in the treatment of chronic obstructive pulmonary disease (COPD) complicated by pulmonary arterial hypertension. METHODS: Eighty-six patients who developed COPD and pulmonary arterial hypertension and received treatment from August 2013 to October 2014 were selected and randomly divided into an observation group and a control group using random number table, 43 in each group. Patients in the control group were orally administrated 20 mg of simvastatin, once a day. Patients in the observation group took 0.25g of azithromycin enteric-coated tablets, once a day, besides simvastatin. The treatment course of both groups was six months. Blood gas analysis indexes, forced expiratory volume in first second (FEV1), six minutes walking distance, dyspnea grade and blood lipid parameter were recorded and compared between the two groups. RESULTS: Arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) of the observation group were (68.13±3.03) mmHg and (45.08±2.27) mmHg after treatment, respectively. In the control group, the values were (60.01±4.72) mmHg and (38.93±1.61) mmHg, respectively. The improvement amplitude of the observation group was superior to that of the control group (P<0.05). FEV1, forced vital capacity (FVC) and 6-minutes walking distance of the observation group were (1.08±0.11) L, (2.1±0.2) L and (380.34 ± 31.28) m respectively after treatment, superior to the control group ((0.93±0.09) L, (1.7±0.1) L) and (302.79±29.74) m, and the difference had statistical significance (P<0.05). The levels of peripheral systolic blood pressure (PSBP) and peripheral diastolic blood pressure (PDBP) of patients in the observation group were both lower than those of the control group, and the difference had statistical significance (P<0.05). CONCLUSION: Azithromycin in combination with simvastatin has definite effect in the treatment of COPD in combination with pulmonary arterial hypertension as it can significantly relieve ventilation disturbance, improve lung function, and decrease pulmonary arterial pressure. Hence it is worth clinical promotion.

Novel Goal-Directed Hemodynamic Optimization Therapy Based on Major Vasopressor during Corrective Cardiac Surgery in Patients with Severe Pulmonary Arterial Hypertension: A Pilot Study.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a common and fatal complication of congenital heart disease (CHD). PAH-CHD increases the risk for postoperative complications. Recent evidence suggests that perioperative goal-directed hemodynamic optimization therapy (GDHOT) significantly improves outcomes in surgery patients. Standard GDHOT is based on major solution volume, vasodilators and inotropic therapy, while novel GDHOT is based on major vasopressor and inotropic therapy. Therefore, we tested whether standard or novel GDHOT improves surgical outcomes in PAH-CHD patients. METHODS: Forty PAH-CHD patients with a ventricular septal defect (VSD) and mean pulmonary arterial pressure (mPAP) >50 mmHg, who were scheduled for corrective surgery, were randomly assigned to 2 groups: SG (study group, n = 20) and CG (control group, n = 20). SG patients received perioperative hemodynamic therapy guided by novel GDHOT, while CG patients received standard GDHOT. Outcome data were recorded up to 28 days postoperatively. Ventilator time, length of ICU stay, and mortality were the primary endpoints. RESULTS: There were no significant differences in preoperative data, surgical procedure, and hospital mortality rates between the 2 groups. Time of mechanical ventilation and length of ICU stay were significantly shorter in SG patients compared to CG patients (P < .05, n = 20). Patients in SG showed a significantly increased systemic vascular resistance index and decreased cardiac index, but no change in pulmonary vascular resistance index at 12 and 24 hours after surgery compared to the controls (P < .05). Patients in SG had significantly decreased PAP, pulmonary arterial pressure/systemic arterial pressure (Pp/Ps), and RVSWI (right ventricular stroke work index) at 12 and 24 hours after surgery (P < .05, respectively). Patients in SG also showed significantly decreased central venous pressure at 4, 12, and 24 hours after surgery compared to those treated with standard protocol (P < .05). CONCLUSION: Our study provides clinical evidence that perioperative goal-directed hemodynamic optimization therapy based on major vasopressor is associated with reduced duration of postoperative respiratory support, and length of ICU stay in PAH-CHD patients undergoing elective surgery. These outcomes, then, may be linked to improved hemodynamics and preservation of right ventricular dynamic function.

[The applications and advantages of Drosophila melanogaster in cancer research].

The common fruit fly, Drosophila melanogaster, has been used to study human disease as a model organism for many years. Many basic biological, physiological, and neurological properties are conserved between mammals and fly. Moreover, Drosophila melanogaster has its unique advantage as a model organism. Recent studies showed that the high level of signaling pathway conservation in tumorigenesis between fly and human and its feasible genetic operation make fly an effective model for oncology research. Numerous research findings showed Drosophila melanogaster was an ideal model for studying the molecular mechanisms of tumorigenesis, invasion and metastasis. This review mainly focuses on the advantages of Drosophila melanogaster in cancer research, established models used for the research of specific cancers and prospective research direction of oncology. It is hoped that this paper can provide insight for cancer research and development of anti-cancer drugs.

A nomogram based on MRI radiomics features of mesorectal fat for diagnosing T2- and T3-stage rectal cancer.

PURPOSE: To develop and validate a nomogram for the preoperative diagnosis of T2 and T3 stage rectal cancer using MRI radiomics features of mesorectal fat. METHODS: The data of 288 patients with T2 and T3 stage rectal cancer were retrospectively collected. Radiomics features were extracted from the lesion region of interest (ROI) in the MRI high-resolution T2WI, apparent diffusion coefficient (ADC), and diffusion-weighted imaging (DWI) sequences. After using ICC inter-group consistency analysis and Pearson correlation analysis to reduce dimensions, LASSO regression analysis was performed to select features and calculate Rad-score for each sequence. Then, Combined_Radscore and nomogram were constructed based on the LASSO-selected features and clinical data for each sequence. Receiver operating characteristic curve (ROC) area under the curve (AUC) was used to evaluate the performance of the Rad-score model and nomogram. Decision curve analysis (DCA) was performed to evaluate the clinical usability of the radiomics nomogram, which were combined with calibration curves to evaluate the prediction accuracy. RESULTS: The nomogram based on MRI-report T status and Combined_Radscore achieved AUCs of 0.921 and 0.889 in the training and validation cohorts, respectively. CONCLUSION: The nomogram can be stated that the radiomics nomogram based on multi-sequence MRI imaging of the mesorectal fat has excellent diagnosing performance for preoperative differentiation of T2 and T3 stage rectal cancer.

A Triterpene-Based bioactive drug delivery system for combined chemotherapy of liver cancer.

Carrier materials always account for the majority particularly in nanosized formulations, which are administrated along with the active ingredient part might result in metabolism related toxicity. The usage of bioactive excipients could not only reduce the sided effect but also provide additional therapeutic effects. In the present study, a triterpene based micellar drug delivery system was developed using a bioactive solanesol derivative. Solanesylamine was prepared firstly followed by conjugating with poly (ethylene glycol) using maleic acid amide linkage. The amphiphilic drug carrier PEGylated (2-propyl-3-methylmaleic acid)-block-solanesol amine (mPEG-CDM-NH-SOL) could be formed into micelles and loaded with doxorubicin (DOX) inside. The micelles were about 112 nm in size and the drug loading content was about 5.97 wt%. An acid triggered drug release behavior was obviously observed for the DOX loaded pH-sensitive micelle mPEG-CDM-NH-SOL-DOX. While not for DOX-loaded micelles without pH-sensitivity (mPEG-NHS-NH-SOL). CCK8 assay showed that the micelles of PEGylated solanesylamines exhibited certain inhibitory effect on tumor cells at high concentration and the pH sensitive ones seemed more toxic. In vivo studies showed that the pH sensitive mPEG-CDM-NH-SOL-DOX had a superior anti-tumor effect, indicating its great potential in cancer treatment.

Identifying CTH and MAP1LC3B as ferroptosis biomarkers for prognostic indication in gastric cancer decoding.

Gastric cancer (GC), known for its high incidence and poor prognosis, urgently necessitates the identification of reliable prognostic biomarkers to enhance patient outcomes. We scrutinized data from 375 GC patients alongside 32 non-cancer controls, sourced from the TCGA database. A univariate Cox Proportional Hazards Model (COX) regression was employed to evaluate expressions of ferroptosis-related genes. This was followed by the application of Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate COX regression for the development of prognostic models. The composition of immune cell subtypes was quantified utilizing CIBERSORT, with their distribution in GC versus control samples being comparatively analyzed. Furthermore, the correlation between the expressions of Cystathionine Gamma-Lyase (CTH) and Microtubule Associated Protein 1 Light Chain 3 Beta (MAP1LC3B) and the abundance of immune cell subtypes was explored. Our bioinformatics findings underwent validation through immunohistochemical analysis. Our prognostic models integrated CTH and MAP1LC3B. Survival analysis indicated that patients categorized as high-risk, as defined by the model, exhibited significantly lower survival rates compared to their low-risk counterparts. Notably, CTH expression inversely correlated with monocyte levels, while MAP1LC3B expression showed an inverse relationship with the abundance of M2 macrophages. Immunohistochemical validation corroborated lower expressions of CTH and MAP1LC3B in GC tissues relative to control samples, in concordance with our bioinformatics predictions. Our study suggests that the dysregulation of CTH, MAP1LC3B, and the accompanying monocyte-macrophage dynamics could be pivotal in the prognosis of GC. These elements present potential targets for prognostic assessment and therapeutic intervention.