Asymmetric catalytic synthesis of chiral covalent organic framework composite (S)-DTP-COF@SiO2 for HPLC enantioseparations by normal-phase and reversed-phase chromatographic modes.

A novel CCOF core-shell composite material (S)-DTP-COF@SiO2 was prepared via asymmetric catalytic and in situ growth strategy. The prepared (S)-DTP-COF@SiO2 was utilized as separation medium for HPLC enantioseparation using normal-phase and reversed-phase chromatographic modes, which displays excellent chiral separation performance for alcohols, esters, ketones, and epoxides, etc. Compared with chiral commercial chromatographic columns (Chiralpak AD-H and Chiralcel OD-H columns) and some previously reported chiral CCOF@SiO2 (CC-MP CCTF@SiO2 and MDI-ß-CD-modified COF@SiO2)-packed columns, there are 4, 3, 13, and 15 tested racemic compounds that could not be resolved on the Chiralpak AD-H column, Chiralcel OD-H column, CC-MP CCTF@SiO2 column, and MDI-ß-CD-modified COF@SiO2 column, respectively, which indicates that the resolution effect of (S)-DTP-COF@SiO2-packed column can be complementary to the other ones. The effects of the analyte mass, column temperature, and mobile phase composition on the enantiomeric separation were investigated. The chiral column exhibits good reproducibility after multiple consecutive injections. The RSDs (n = 5) of the peak area and retention time were less than 1.5% for repetitive separation of 2-methoxy-2-phenylethanol and 1-phenyl-1-pentanol. The chiral core-shell composite (S)-DTP-COF@SiO2 exhibited good enantiomeric separation performance, which not only demonstrates its potential as a novel CSP material in HPLC but also expands the range of applications for chiral COFs.

Pulmonary hypertension- a novel phenotypic hypothesis of Kabuki syndrome: a case report and literature review.

BACKGROUND: Pediatric pulmonary hypertension (PH) is a serious and rare disease that is often derived from genetic mutations. Kabuki syndrome (KS) is a chromosomal abnormality disease that has its origin in the mutation of lysine methyltransferase 2D(KMT2D). Recent evidence has shown that KMT2D mutations are associated with pediatric pulmonary disorders. However, the relationship between the clinical courses of PH and the KMT2D mutation is reported in extremely few cases. Therefore, in this paper, a case was presented and previous literature was reviewed for better understanding of the correlation between pediatric PH and KMT2D mutations. CASE PRESENTATION: A 3-year-old girl was transferred to our center for severe cough, shortness of breath, fatigue and fever. Physical examination revealed facial deformities and growth retardation. Echocardiography showed a small atrial septal defect (ASD), and right heart catheterization indicated a significant increase in pulmonary vascular pressure and resistance. The genetic test suggested that she had a KMT2D gene mutation. The patient was finally diagnosed with KS. She was given targeted drugs to reduce pulmonary vascular pressure, but the effect was unsatisfactory. CONCLUSIONS: KS can be complicated with multiple organ malformations and dysfunction. With the progress of next generation sequencing, an increasing number of new phenotypes related to KMT2D mutations have been reported. A bold hypothesis is proposed in this article, that is, PH may be a new phenotype associated with KMT2D mutations. It is suggested that KS and PH should be differentiated from each other to avoid delayed diagnosis and treatment in clinical practice. There is no specific drug for KS treatment. The prognosis of children with inherited PH is usually poor, and lung transplantation may increase their survival rates.

Correlation between individual physical characteristics and spinal cerebrospinal fluid volume.

Spinal cerebrospinal fluid (CSF) volume is the primary determinant for the spread of spinal anesthesia. However, it cannot generally be obtained during spinal anesthesia, and patient physical characteristics are always adopted to obtain a suitable spinal spread. In this study, we sought to explore the relationship between individual physical characteristics and thoracosacral CSF volume to provide a theoretical basis for more accurate spinal anesthesia. In total 35 healthy volunteers were enrolled in this study. Three-dimensional magnetic resonance imaging was used to reconstruct and measure the spinal CSF volume. Physical characteristics and spinal CSF volume were recorded. Bivariate and multiple linear regression analyses were used to analyze the correlation between the individual physical characteristics and thoracosacral CSF volume. Total of 31 participants were included in the final analysis. Bivariate linear correlation analysis showed that the volume of thoracosacral CSF was correlated with both individual dorso-sacral distance and height (both p < 0.01), but not with abdominal girth (p > 0.05). Multiple linear regression analyses revealed that the adjusted R2 values were 0.404 for the regression equation between thoracosacral CSF volume, dorso-sacral distance, and abdominal girth. Our study showed that dorso-sacral distance and abdominal girth were essential factors contributing to thoracosacral CSF volume. A longer dorso-sacral distance and smaller abdominal girth mean larger spinal CSF volume.

[Research Progress in the Application of Terahertz Spectroscopy and Imaging Technology in Stomatology].

Terahertz waves, the electromagnetic waves in the range of 0.1 to 10 THz, has the advantages of being damage-free, causing no ionizing radiation injury, and being capable of recognizing the fingerprint spectrum of molecular characteristics, thus holding encouraging prospects for wide applications in the field of biomedicine. Terahertz spectrum can be used to identify and characterize biological structures of different levels, from biomolecules such as proteins to cells and tissues, through the spectral signals and/or restored images of the samples. Herein, we summarized the current stomatogical application of and research progress in terahertz spectroscopy and imaging in dentistry, reported the latest research findings, strengths and limitations from three perspectives, tooth anatomical structure, the extent of caries progression, and oral soft tissue, and suggested possible directions for future exploration.

Comparative study of 1064 nm nanosecond, 1064 nm picosecond, 755 nm, and 595 nm lasers for tattoo removal: An essential role by macrophage.

OBJECTIVES: Tattoo removal is in high demand, and many types of lasers can be used for tattoo removal. Macrophages play an important role in the persistence of tattoos. However, comparative studies of the efficacy of tattoo removal with different lasers versus the relationship between the destruction of pigment particles or recruitment of macrophages after laser treatment are lacking. MATERIALS AND METHODS: Tattoo models were established on the rat dorsal surface and randomly treated with 1064 nm nanosecond, 1064 nm picosecond, 755 nm, and 595 nm lasers for one session. Clinical photographic evaluation, melanin index, hematoxylin and eosin staining, identification of macrophages by CD68 staining, and transmission electron microscopy were conducted at different time points. RESULTS: Regardless of the pulse duration, all lasers included were effective for the removal of black tattoos, with 1064 nm lasers having the best efficacy, followed by 755 and 595 nm lasers. The diameter of the pigment particles and recruitment of dermal macrophages correlated with the efficacy of tattoo removal. CONCLUSIONS: In this study, the 1064 nm lasers were found to be the most effective for black tattoo removal. However, there was no significant difference between the 1064 nm picosecond and the nanosecond lasers. Macrophage recruitment plays an essential role in pigment metabolism during laser-tattoo removal.

Evaluation of radial and ulnar artery blood flow after radial artery decannulation using colour Doppler ultrasound.

BACKGROUND: There is a lack of reports in the literature regarding changes in radial artery blood flow after decannulation. The objective of this study was to investigate changes in radial and ulnar artery blood flow after radial artery decannulation using Doppler ultrasound and to explore the factors that influence radial artery blood flow recovery. METHODS: In current observational study, we used colour Doppler ultrasound to measure the cross-sectional area of the radial (SR) and ulnar artery (SU) and peak systolic velocity of the radial (PSVR) and ulnar artery (PSVU) for both hands at four time points in patients with radial artery cannulation: pre-cannulation (T0), 30 min after decannulation (T1), 24 h after decannulation (T2), and 7 days after decannulation (T3). Repeated measures analysis of variance and logistic regression analysis were performed to analyse the data. RESULTS: Overall, 120 patients were included in the present study. We obtained the following results on the side ipsilateral to the cannulation: compared with T0, the ratio of PSVU/PSVR increased significantly at T1 and T2 (p < 0.01); compared with T1, the ratio of PSVU/PSVR decreased significantly at T2 and T3 (p < 0.01); compared with T2, the ratio of PSVU/PSVR decreased significantly at T3 (p < 0.01). Female sex (OR, 2.76; 95% CI, 1.01-7.57; p = 0.048) and local hematoma (OR 3.04 [1.12-8.25]; p = 0.029) were factors that were significantly associated with the recovery of radial artery blood flow 7 days after decannulation. CONCLUSIONS: There was a compensatory increase in blood flow in the ulnar artery after ipsilateral radial artery decannulation. Female sex and local hematoma formation are factors that may affect the recovery of radial artery blood flow 7 days after catheter removal.

Anesthetic strategy for obese patients during gastroscopy: deep sedation or conscious sedation? A prospective randomized controlled trial.

OBJECTIVE: This paper aims to compare the incidence of SpO2 values < 95% and < 90% of the obese patients between conscious sedation and deep sedation and whether conscious sedation was superior to the deep sedation for obese patients during diagnostic gastroscopy. METHODS: Obese patients undergoing diagnostic gastroscopy were randomly assigned to two different intervention groups: group CS (conscious sedation) or group DS (deep sedation). Group CS patients were managed by conscious sedation [Modified Observer Assessment of Alertness/Sedation (MOAA/S) at 4-5] protocol, and group DS patients were managed by deep sedation (MOAA/S at ≤ 2) protocol. Propofol and sufentanil (0.1 and 0.05 mg/kg) were, respectively, infused for sedation and analgesia in CS and DS protocols. The primary endpoints were to compare the incidence of SpO2 values < 95% and < 90% of the patients between the two groups. The incidence of successful sedation, satisfaction scores of patients and endoscopist were assessed as secondary endpoints. RESULTS: 115 obese patients (59 in group CS and 56 in group DS) were enrolled in this study. The incidences of SpO2 < 95% and < 90% in group CS (42.4% and 6.8%) were significantly lower than those in group DS (69.6% and 19.6%, with P = 0.003 and 0.041, respectively). The incidence of successful sedation was similar between groups (86.4% vs 89.3%, P = 0.641). Patient satisfaction scores and endoscopist satisfaction scores were both similar between groups (P = 0.548 and 0.171). CONCLUSION: Conscious sedation with propofol and sufentanil (0.1 mg/kg) reduced the incidence of hypoxic events without affecting gastroscopy procedure and satisfaction compared with the deep sedation for obese patients during diagnostic gastroscopy. TRIAL REGISTRATION: ChiCTR-1900024894; registration date, July 31, 2019. http://www.chictr.org.cn .

The Application Value of Magnetic Resonance Imaging (MRI) in the Clinical Diagnosis in Hospital Management.

BACKGROUND & OBJECTIVE: To evaluate the application value of dynamic enhanced magnetic resonance imaging (DCE-MRI) in the clinical diagnosis in hospital based on the fuzzy C-means clustering algorithm and conduct its cost-benefit analysis in practice. METHODS: This study was conducted from October 11th 2020 to November 25, 2020. Eighteen patients with lung cancer confirmed by pathology were collected and examined by DCE-MRI one day before and one month after surgery using a fuzzy C-means clustering algorithm. And then, taking Guang'an District People's Hospital as an example, the present paper conducts the cost-benefit analysis with the utilization of net present value (NPV). RESULTS: After 1-month review, eleven patients with effective treatment, four numerical Ktrans, Kep, Ve, Vp compared with preoperative decreased, which Ktrans, Kep, the change of the Ve was statistically significant (P < 0.05), the Vp of decline has no statistical significance (P > 0.05), the experimental and ineffective group after an operation, compared to four numerical Ktrans and Vp difference was statistically significant (P < 0.05), the corresponding AUC (area under the curve) to 1 and 0.818, the sensitivity of 100% and 85.7%, a specific degree of 100% and 72.7%. The NPV analysis results showed that the hospital could achieve profit and loss balance in the third year after purchasing MRI equipment and then gradually obtain positive cash inflow. CONCLUSION: The application of MRI in the Clinical Diagnosis helps hospital promote the therapeutic effect, thus having great practical value, and also contributes to increasing benefits in the long run.

[Effect of calorie-enriched formula on postoperative catch-up growth in infants with cyanotic congenital heart disease: a propective randomized controlled study].

OBJECTIVE: To study the effect of calorie-enriched formula on postoperative catch-up growth in infants with cyanotic congenital heart disease (CHD). METHODS: A total of 100 infants with cyanotic CHD who underwent surgical operation from January to December, 2017, were randomly divided into a high-calorie group (receiving calorie-enriched formula after surgery) and a conventional group (receiving standard formula after surgery), with 50 infants in each group. All infants were followed up for 6 months. The observation indices included body height, body weight, prealbumin, and N-terminal pro-brain natriuretic peptide before surgery, at the time of ventilator weaning and extubation after surgery, and at 1, 3, and 6 months after surgery. Height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and weight-for-height Z-score (WHZ) were also assessed. Adverse reactions were recorded for both groups. RESULTS: There were 25 cases (50%) and 21 cases (42%) of malnutrition in the high-calorie group and the conventional group respectively before surgery (P > 0.05). The nutritional status of the two groups improved 6 months after surgery (P < 0.05). At 6 months after surgery, compared with the conventional group, the high-calorie group had a lower proportion of infants with malnutrition (18% vs 36%, P < 0.05) and also a lower proportation of infants with a WAZ score of < -2 (P < 0.05). The infants with malnutrion in the high-calorie group had higher HAZ, WAZ, and WHZ than those in the conventional group (P < 0.05). No gastrointestinal intolerance was observed in both groups during hospitalization. CONCLUSIONS: Compared with the standard formula, calorie-enriched formula can better help with postoperative catch-up growth in infants with cyanotic CHD.

Protective effect of baicalin against cognitive memory dysfunction after splenectomy in aged rats and its underlying mechanism.

Postoperative cognitive dysfunction is a common neurological complication, characterized by impaired learning and memory, that occurs after anesthesia and surgery, especially in elderly patients. The traditional Chinese medicine baicalin is known to have neuroprotective effects. Therefore, we have investigated whether baicalin can improve postoperative cognitive impairment in aged rats after splenectomy. A total of 60 Sprague Dawley rats were randomly divided, equally, into the splenectomy, sham operation (Sham), low-dose baicalin (Baicalin A), medium-dose baicalin (Baicalin B), and high-dose baicalin (Baicalin C) groups. Splenectomy was performed under anesthesia in all groups except for the Sham group, in which an appropriate concentration of saline was administered. The effects of baicalin on learning and memory were examined by the Y-maze behavioral experiments. Although splenectomy had a negative effect on cognitive function in the acute phase, all the rats spontaneously recovered on a postoperative day seven. Nonetheless, in the acute phase, the medium and high doses of baicalin slightly alleviated these effects of the procedure. The protein expression of the inflammatory cytokines tumor necrosis factor-α, Interleukin-6, and Interleukin-1ß was assessed using enzyme-linked immunosorbent assay. Their levels were elevated in the acute phase but were returned to normal with the medium and high dose of baicalin. Real-time PCR analysis of the mRNA expression of the N-methyl-D-aspartic acid receptor TNF-α, which is known to be involved in long-term potentiation, revealed that baicalin promoted its transcription. Thus, the findings indicate that baicalin may improve postoperative cognitive memory dysfunction in postoperative cognitive dysfunction in rats via anti-inflammatory mechanisms and pathways that involve N-methyl-D-aspartate receptor 2B subunit.

Real-time Microwave Exposure Induces Calcium Efflux in Primary Hippocampal Neurons and Primary Cardiomyocytes.

OBJECTIVE: To detect the effects of microwave on calcium levels in primary hippocampal neurons and primary cardiomyocytes by the real-time microwave exposure combined with laser scanning confocal microscopy. METHODS: The primary hippocampal neurons and primary cardiomyocytes were cultured and labeled with probes, including Fluo-4 AM, Mag-Fluo-AM, and Rhod-2, to reflect the levels of whole calcium [Ca2+], endoplasmic reticulum calcium [Ca2+]ER, and mitochondrial calcium [Ca2+]MIT, respectively. Then, the cells were exposed to a pulsed microwave of 2.856 GHz with specific absorption rate (SAR) values of 0, 4, and 40 W/kg for 6 min to observe the changes in calcium levels. RESULTS: The results showed that the 4 and 40 W/kg microwave radiation caused a significant decrease in the levels of [Ca2+], [Ca2+]ER, and [Ca2+]MIT in primary hippocampal neurons. In the primary cardiomyocytes, only the 40 W/kg microwave radiation caused the decrease in the levels of [Ca2+], [Ca2+]ER, and [Ca2+]MIT. Primary hippocampal neurons were more sensitive to microwave exposure than primary cardiomyocytes. The mitochondria were more sensitive to microwave exposure than the endoplasmic reticulum. CONCLUSION: The calcium efflux was occurred during microwave exposure in primary hippocampal neurons and primary cardiomyocytes. Additionally, neurons and mitochondria were sensitive cells and organelle respectively.

Real-time Assessment of Cytosolic, Mitochondrial, and Nuclear Calcium Levels Change in Rat Pheochromocytoma Cells during Pulsed Microwave Exposure Using a Genetically Encoded Calcium Indicator.

Little information is available about the effects of exposure to pulsed microwaves on neuronal Ca2+ signaling under non-thermal conditions. In this study, rat pheochromocytoma (PC12) cells were exposed to pulsed microwaves for 6 min at a specific absorption rate (SAR) of 4 W/kg to assess possible real-time effects. During microwave exposure, free calcium dynamics in the cytosol, mitochondria, and nucleus of cells were monitored by time-lapse microfluorimetry using a genetically encoded calcium indicator (ratiometric-pericam, ratiometric-pericam-mt, and ratiometric-pericam-nu). We established a waveguide-based real-time microwave exposure system under accurately controlled environmental and dosimetric conditions and found no significant changes in the cytosolic, mitochondrial, or nuclear calcium levels in PC12 cells. These findings suggest that no dynamic changes occurred in [Ca2+]c, [Ca2+]m, or [Ca2+]n of PC12 cells at the non-thermal level.

Microwave-induced Apoptosis and Cytotoxicity of NK Cells through ERK1/2 Signaling.

OBJECTIVE: To investigate microwave-induced morphological and functional injury of natural killer (NK) cells and uncover their mechanisms. METHODS: NK-92 cells were exposed to 10, 30, and 50 mW/cm2 microwaves for 5 min. Ultrastructural changes, cellular apoptosis and cell cycle regulation were detected at 1 h and 24 h after exposure. Cytotoxic activity was assayed at 1 h after exposure, while perforin and NKG2D expression were detected at 1 h, 6 h, and 12 h after exposure. To clarify the mechanisms, phosphorylated ERK (p-ERK) was detected at 1 h after exposure. Moreover, microwave-induced cellular apoptosis and cell cycle regulation were analyzed after blockade of ERK signaling by using U0126. RESULTS: Microwave-induced morphological and ultrastructural injury, dose-dependent apoptosis (P < 0.001) and cell cycle arrest (P < 0.001) were detected at 1 h after microwave exposure. Moreover, significant apoptosis was still detected at 24 h after 50 mW/cm2 microwave exposure (P < 0.01). In the 30 mW/cm2 microwave exposure model, microwaves impaired the cytotoxic activity of NK-92 cells at 1 h and down regulated perforin protein both at 1 h and 6 h after exposure (P < 0.05). Furthermore, p-ERK was down regulated at 1 h after exposure (P < 0.05), while ERK blockade significantly promoted microwave-induced apoptosis (P < 0.05) and downregulation of perforin (P < 0.01). CONCLUSION: Microwave dose-dependently induced morphological and functional injury in NK-92 cells, possibly through ERK-mediated regulation of apoptosis and perforin expression.

Microwave-Induced Structural and Functional Injury of Hippocampal and PC12 Cells Is Accompanied by Abnormal Changes in the NMDAR-PSD95-CaMKII Pathway.

Recent studies have highlighted the important role of the postsynaptic NMDAR-PSD95-CaMKII pathway for synaptic transmission and related neuronal injury. Here, we tested changes in the components of this pathway upon microwave-induced neuronal structure and function impairments. Ultrastructural and functional changes were induced in hippocampal neurons of rats and in PC12 cells exposed to microwave radiation. We detected abnormal protein and mRNA expression, as well as posttranslational modifications in the NMDAR-PSD95-CaMKII pathway and its associated components, such as synapsin I, following microwave radiation exposure of rats and PC12 cells. Thus, microwave radiation may induce neuronal injury via changes in the molecular organization of postsynaptic density and modulation of the biochemical cascade that potentiates synaptic transmission.

Middle finger length-based tracheal intubation depth improves the rate of appropriate tube placement in children.

BACKGROUND: It is challenging for anesthetists to determine the optimal tracheal intubation depth in children. We hypothesize that a measure three times the length of the middle finger can be used for predicting tracheal tube depth in children. METHODS: Eighty-six children (4-14 years of age) were included in this study. After the children were anesthetized, a fiberoptic bronchoscope (FOB) was inserted into the trachea, the lengths from the upper incisor teeth to carina and vocal cords were measured, and a suitably sized cuffed tracheal tube was inserted into the trachea. Age-based and middle finger length-based formulas were used to determine the tracheal intubation depth. RESULTS: All 86 children enrolled were included in this study. Compared with the age-based intubation, the rate of appropriate tube placement was higher for middle finger length-based intubation (88.37% vs 66.28%, P = 0.001). The proximal intubation rate was lower in middle finger length-based intubation (4.65% vs 32.56%, P < 0.001). There was only weak evidence for a difference in the distal intubation rate between the two methods (6.97% vs 1.16%, P = 0.054). The correlation coefficient between middle finger length and optimal tracheal tube depth was larger than that between age and optimal tracheal tube depth (0.883 vs 0.845). CONCLUSIONS: Our data indicate that the appropriate tube placement rate can be improved by using three times the middle finger length as the tracheal intubation depth in children.

Microwave exposure impairs synaptic plasticity in the rat hippocampus and PC12 cells through over-activation of the NMDA receptor signaling pathway.

OBJECTIVE: The aim of this study is to investigate whether microwave exposure would affect the N-methyl-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity impairment. METHODS: 48 male Wistar rats were exposed to 30 mW/cm2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H&E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. RESULTS: Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and related signaling molecules (Ca2+/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein) were examined. CONCLUSION: 30 mW/cm2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.

Subcomponent self-assembly construction of tetrahedral cage FeII4L4 for high-resolution gas chromatographic separation.

Metal organic cages (MOCs), as an emerging discrete supramolecular compounds, have received widespread attention in separation, biomedicine, gas capture, catalysis, and molecular recognition due to their porosity, adjustability and stability. Herein, we present a new chiral MOC FeII4L4 coated capillary column prepared for gas chromatographic (GC) separation of different types of organic compounds, including n-alkanes, n-alcohols, alkylbenzenes, isomers, especially for racemic compounds. There are 20 different kinds of racemates (e.g., alcohols, ethers, epoxides, esters, alkenes, and aldehydes) were well resolved on the FeII4L4 chiral column and a maximum resolution value for 1-phenyl-1-propanol reaches 6.17. The FeII4L4 coated column exhibited high column efficiency (3100 plates m-1 for n-dodecane) and good enantiomeric resolution complementary to that of a commercial ß-DEX 120 column and the previously reported chiral MOC [Fe4L6] (ClO4)8 coated column. The relative standard deviation (RSDs) of the peak area and retention time of glycidol and nitrotoluene were below 1.2 %. This study reveals that chiral MOCs have good application prospects in chromatographic separation.

[Efficacy of endothelin receptor antagonist bosentan on the long-term prognosis in patients after Fontan operation].

OBJECTIVE: To investigate the long-term effect of bosentan on outcome in patients after Fontan operation. METHODS: Patients after Fontan surgery were randomly divided into bosentan group (B, n = 16) and control group (C, n = 23). Bosentan was applied within 7 days after Fontan surgery as follows: at the first month, 7.8125 mg Bid for patients with body weight ≤ 10 kg; 15.625 mg Bid for patients with body weight between 10-20 kg; 31.25 mg Bid for patients with body weight 20-30 kg and 62.5 mg Bid for patients with body weight > 30 kg. At the second month, the bosentan dose was doubled and Bosentan therapy was continued for more than 1 year. Group C didn't take drugs affecting pulmonary artery pressure. All patients were followed up for 2 years and incidence of mortality, protein losing enteropathy, pulmonary arteriovenous fistulae, 6-minute walk test, heart function were compared between the two groups. RESULTS: After 2 years, mortality tended to be lower in group B compared to group C [6.25% (1/16) vs. 21.8% (5/23), P > 0.05]. Incidence of pulmonary arteriovenous fistulae and protein losing enteropathy were significantly lower in group B than in group C (6.25% vs. 34.78%, P = 0.01;6.25% vs. 39.13%, P = 0.02, respectively) . The results of 6-minute walk test[ (485 ± 44) m vs. (302 ± 183) m] and heart function in group B (3 NYHA III/IV patients in group B vs. 14 NYHA III/IV patients in group C, all P < 0.05) were all better than group C. The concentrations of vasoactive factors such as brain natriuretic peptide (BNP, 279.07 ± 128.17 vs. 457.67 ± 221.30), endothelin (ET, 3.30 ± 0.61 vs. 4.98 ± 1.24) and thromboxane (TXA2, 97.2 ± 24.0 vs. 163.22 ± 24.4) were also significantly lower in group B than in group C (all P < 0.05). Prostacyclin (PGI2) level and incidence of arrhythmias were similar between the two groups. There was no thrombotic event in both groups during follow up. CONCLUSION: Bosentan trerapy in patients post Fontan operation could reduce the incidence of pulmonary arteriovenous fistulae and protein losing enteropathy and improve heart function.

Non-classic radiation-induced liver disease after intensity-modulated radiotherapy for Child-Pugh grade B patients with locally advanced hepatocellular carcinoma.

BACKGROUND: The incidence of classic radiation-induced liver disease (cRILD) has been significantly reduced. However, non-classic radiation-induced liver disease (ncRILD) remains a major concern following radiotherapy in patients with hepatocellular carcinoma (HCC). This study evaluated the incidence of ncRILD following intensity-modulated radiotherapy (IMRT) for Child-Pugh grade B (CP-B) patients with locally advanced HCC and established a nomogram for predicting ncRILD probability. METHODS: Seventy-five CP-B patients with locally advanced HCC treated with IMRT between September 2014 and July 2021 were included. The max tumor size was 8.39 cm ± 5.06, and the median prescribed dose was 53.24 Gy ± 7.26. Treatment-related hepatotoxicity was evaluated within three months of completing IMRT. A nomogram model was formulated to predict the probability of ncRILD, using univariate and multivariate analysis. RESULTS: Among CP-B patients with locally advanced HCC, ncRILD occurred in 17 (22.7%) patients. Two patients (2.7%) exhibited a transaminase elevation of ≥ G3, fourteen (18.7%) exhibited a Child-Pugh score increase of ≥ 2, and one (1.3%) demonstrated both a transaminase elevation of ≥ G3 and a Child-Pugh score increase of ≥ 2. No cRILD cases were observed. A mean dose to the normal liver of ≥ 15.1 Gy was used as the cutoff for ncRILD. Multivariate analysis revealed that the prothrombin time before IMRT, tumour number, and mean dose to the normal liver were independent risk factors for ncRILD. The nomogram established on the basis of these risk factors displayed exceptional predictive performance (AUC = 0.800, 95% CI 0.674-0.926). CONCLUSIONS: The incidence of ncRILD following IMRT for CP-B patients with locally advanced HCC was acceptable. A nomogram based on prothrombin time before IMRT, tumour number, and mean dose to the normal liver accurately predicted the probability of ncRILD in these patients.

Radiotherapy plus anti-PD1 versus radiotherapy for hepatic toxicity in patients with hepatocellular carcinoma.

PURPOSE: In this study, we aimed to compare the radiation-induced hepatic toxicity (RIHT) outcomes of radiotherapy (RT) plus antibodies against programmed cell death protein 1 (anti-PD1) versus RT alone in patients with hepatocellular carcinoma (HCC), evaluate prognostic factors of non-classic radiation-induced liver disease (ncRILD), and establish a nomogram for predicting the probability of ncRILD. PATIENTS AND METHODS: Patients with unresectable HCC treated with RT and anti-PD1 (RT + PD1, n = 30) or RT alone (n = 66) were enrolled retrospectively. Patients (n = 30) in each group were placed in a matched cohort using propensity score matching (PSM). Treatment-related hepatotoxicity was evaluated and analyzed before and after PSM. The prognostic factors affecting ncRILD were identified by univariable logistic analysis and Spearman's rank test in the matched cohort to generate a nomogram. RESULTS: There were no differences in RIHT except for increased aspartate aminotransferase (AST) ≥ grade 1 and increased total bilirubin ≥ grade 1 between the two groups before PSM. After PSM, AST ≥ grade 1 occurred more frequently in the RT + PD1 group (p = 0.020), and there were no significant differences in other hepatotoxicity metrics between the two groups. In the matched cohort, V25, tumor number, age, and prothrombin time (PT) were the optimal prognostic factors for ncRILD modeling. A nomogram revealed a good predictive performance (area under the curve = 0.82). CONCLUSIONS: The incidence of RIHT in patients with HCC treated with RT + PD1 was acceptable and similar to that of RT treatment. The nomogram based on V25, tumor number, age, and PT robustly predicted the probability of ncRILD.