Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD. Methods: Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected. Results: YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment. Conclusions: YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

Isoquercitrin attenuates the progression of non-alcoholic steatohepatitis in mice by modulating galectin-3-mediated insulin resistance and lipid metabolism.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a global health problem with no effective treatment. Isoquercitrin (IQ) alters hepatic lipid metabolism and inhibits adipocyte differentiation. The underlying regulatory mechanisms of IQ in regulating insulin resistance (IR) and lipid metabolism remain unclear. PURPOSE: This study was aimed at investigating the effects of IQ on NASH and deciphering whether the underlying mechanisms are via modulation of galectin-3 mediated IR and lipid metabolism. METHODS: IR-HepG2 cell lines were used to demonstrate the ability of IQ to modulate galectin-3-mediated glucose disposal and lipid metabolism. A 20-week high-fat diet (HFD)-induced NASH model was established in C57BL/6J mice, and the protective effect of IQ on lipid disposal in the liver was verified. Further, the mRNA and protein levels of glucose and lipid metabolism were investigated, and lysophosphatidylcholine (LPC) and acylcarnitine (AC) profiling were performed to characterize the changes in endogenous substances associated with mitochondrial function and lipid metabolism in serum and cells. Furthermore, the pharmacokinetic features of IQ were explored in a rat model of NASH. RESULTS: IQ restored liver function and ameliorated inflammation and lipid accumulationin NASH model mice. Notably, significant regulation of the proteins included fatty acid-generating and transporting, cholesterol metabolism enzymes, nuclear transcription factors, mitochondrial metabolism, and IR-related enzymes was noted to be responsible for the therapeutic mechanisms of IQ against experimental NASH. Serum lipid metabolism-related metabolomic assay confirmed that LPC and AC biosynthesis mostly accounted for the therapeutic effect of IQ in mice with NASH and that IQ maintained the homeostasis of LPC and AC levels. CONCLUSION: This is the first study showing that IQ protects against of NASH by modulating galectin-3-mediated IR and lipid metabolism. The mechanisms responsible for liver protection and improved lipid metabolic disorder by IQ may be related to the suppression of IR and regulation of mitochondrial function and lipid metabolism. Galectin-3 down-regulation represents a potentially novel approach for the treatment and prevention of NASH.

Disseminated Herpes Zoster with Decreased CD4 Counts in a HIV-Infected Patient.

Herpes zoster is typically a blister rash involving a single skin group, caused by the reactivation of primary varicella zoster virus infection. Disseminated herpes zoster refers to the presence of more than 20 small blisters outside the primary or adjacent skin, which is rare and usually occurs in individuals with weakened immune function. This case described a patient diagnosed with disseminated herpes zoster, with a decrease in CD4 count (379 cells/mm3) and certain skin lesions. He was subsequently screened positive for HIV. Also, we summarized other studies on the CD4 value of HIV patients with herpes zoster. Overall, for herpes zoster patients with decreased CD4 levels and certain skin manifestations, such as diffuse, ulcerative, or pustular lesions, clinicians should be aware of HIV infection.

Lymphocytic Thrombophilic Arteritis: A Case Report with a History of 67 Years.

We report the case of a patient with Lymphocytic thrombophilic arteritis (LTA) with a history of 67 years. This is a relatively rare disease with no recognised guidelines for diagnosis and treatment. The long medical history from birth of this patient and the lack of positive progression may provide some new ideas for the treatment of this disease.

Dose evaluation of inter- and intra-fraction prostate motion in extremely hypofractionated intensity-modulated proton therapy for prostate cancer.

Inter- and intra-fractional prostate motion can deteriorate the dose distribution in extremely hypofractionated intensity-modulated proton therapy. We used verification CTs and prostate motion data calculated from 1024 intra-fractional prostate motion records to develop a voxel-wise based 4-dimensional method, which had a time resolution of 1 s, to assess the dose impact of prostate motion. An example of 100 fractional simulations revealed that motion had minimal impact on planning dose, the accumulated dose in 95 % of the scenarios fulfilled the clinical goals for target coverage (D95 > 37.5 Gy). This method can serve as a complementary measure in clinical setting to guarantee plan quality.

The elevated toxicity of the biodegradation product (guanylurea) from metformin and the antagonistic pattern recognition of combined toxicity: Insight from the pharmaceutical risk assessment and the simulated wastewater treatment.

The emerging contaminants metformin (MET) and its degradation product guanylurea (GUA) are released into aquatic environments through wastewater treatment plants (WWTPs). Thus, the environmental risks of wastewater with more treatments may be underestimated due to the lower effect concentration of GUA and the higher detected concentration of GUA in treated wastewater in comparison with MET. In this study, we aimed to investigate the combined toxicity mode of MET and GUA to Brachionus calyciflorus by simulating the degrees of wastewater treatments through adjustments to the ratio of MET and GUA in medium. The results showed that the 24 h-LC50 of MET, GUA, their mixtures of equal concentrations and the mixtures of equal toxic units to B. calyciflorus were 907.44, 544.53, 1185.82 and 940.52 mg/L, respectively, demonstrating GUA is significantly more toxic than MET. An antagonistic interaction between MET and GUA was found in mixture toxicity assessments. Compared with the control, MET treatments only significantly affected the intrinsic rate of population increase of rotifers (rm), while all life-table parameters were significantly affected by GUA. In addition, at medium and high concentrations (120 and 600 µmol/L), the net reproductive rate (R0) and rm of rotifers under GUA were significantly lower than those under MET. Notably, increased proportion of GUA relative to MET in binary-mixture treatments resulted in increased survival risk and reduced fecundity of rotifers. Moreover, the responses of population dynamics to exposures of MET and GUA were mainly attributed to the reproduction of rotifer, indicating that an improved wastewater treatment process is necessary to protect aquatic ecosystems. The study highlights the importance of considering the combined toxicity of emerging contaminants and degradation product in environmental risk assessment, especially the unintentional transformations of parent compound in treated wastewater.

Asymmetric Total Synthesis of Naphthospironone A.

Naphthospironone A, a polyhydroxy cagelike bioactive natural product, was synthesised for the first time in this study. The spiro[bicyclo[3.2.1]octane-pyran] core was constructed by an acid-promoted epoxide-opening lactonisation and a base-induced intramolecular aldol-type cyclisation.

Detecting Hydronephrosis Through Ultrasound Images Using State-of-the-Art Deep Learning Models.

The goal of this study was to assess the feasibility of three models for detecting hydronephrosis through ultrasound images using state-of-the-art deep learning algorithms. The diagnosis of hydronephrosis is challenging because of varying and non-specific presentations. With the characteristics of ready accessibility, no radiation exposure and repeated assessments, point-of-care ultrasound becomes a complementary diagnostic tool for hydronephrosis; however, inter-observer variability still exists after time-consuming training. Artificial intelligence has the potential to overcome the human limitations. A total of 3462 ultrasound frames for 97 patients with hydronephrosis confirmed by the expert nephrologists were included. One thousand six hundred twenty-eight ultrasound frames were also extracted from the 265 controls who had normal renal ultrasonography. We built three deep learning models based on U-Net, Res-UNet and UNet++ and compared their performance. We applied pre-processing techniques including wiping the background to lessen interference by YOLOv4 and standardizing image sizes. Also, post-processing techniques such as adding filter for filtering the small effusion areas were used. The Res-UNet algorithm had the best performance with an accuracy of 94.6% for moderate/severe hydronephrosis with substantial recall rate, specificity, precision, F1 measure and intersection over union. The Res-UNet algorithm has the best performance in detection of moderate/severe hydronephrosis. It would decrease variability among sonographers and improve efficiency under clinical conditions.

Efficacy and safety of upadacitinib for the treatment of moderate-to-severe atopic dermatitis: a meta-analysis of randomized clinical trials.

Introduction: Recent studies have confirmed the possibility of using upadacitinib for treating atopic dermatitis (AD). However, there is no meta-analysis to summarize and quantify the efficacy and safety of the drug, especially for adolescents with AD. Aim: To evaluate the overall efficacy and safety of upadacitinib in adults and adolescents with AD. Material and methods: We developed this systematic review and meta-analysis according to PRISMA guidelines. Risk-of-bias assessment tool, RoB2 (revised version 2019) was used for quality assessment. Results: Four RCTs were enrolled in the analysis, 3 of which on both adults and adolescents, while the other on adults only. For either adults or adolescents, the group treated with upadacitinib all had better performance than controls: EASI-75 (adults): RR = 4.68, 95% CI: 4.09, 5.35; NRS4 (adults): RR = 4.07, 95% CI: 3.15, 5.25; EASI-75 (adolescents): RR = 4.16, 95% CI: 2.70, 6.42; NRS4 (adolescents): RR = 4.52, 95% CI: 2.49, 8.21. Furthermore, upadacitinib 30 mg was more effective than 15 mg. For serious AEs, upper respiratory tract infection and headache, there was no significant difference between the upadacitinib group and controls. However, the treatment of upadacitinib may increase the risk of nasopharyngitis, increase blood creatine phosphokinase and cause acne. Conclusions: Upadacitinib seems to be a promising drug for AD. More long-term and larger-sized randomized clinical trials are required to further assess the safety and efficacy of upadacitinib for AD.

Inhibitory Effects of Antipsychotic Chlorpromazine on the Survival, Reproduction and Population Growth Other Than Neurotransmitters of Zooplankton in Light of Global Warming.

Global warming and environmental pollution have created a unique combination of abiotic and biotic stresses to zooplankton. However, little information is available on the effects of antipsychotic drugs commonly used to treat psychosis, such as chlorpromazine (CPZ), on non-target aquatic organisms in light of global warming. This study investigated how dopamine concentrations (DAC), acute toxicity and chronic toxicity of Brachionus calyciflorus changed in response to CPZ and gradually increasing temperatures. The results showed that the concentration range of rotifer DAC was 1.06~2.51 ng/g. At 18, 25 and 32 °C, the 24 h LC50 was 1.795, 1.242 and 0.833 mg/L, respectively. Compared to the control, exposure to CPZ significantly decreased life expectancy at hatching, the net reproduction rate, generation time, population growth rate and dopamine concentration of B. calyciflorus in all three temperatures (p < 0.05). The toxicity of CPZ to rotifers was increased by high temperature. These findings indicated that CPZ is highly toxic to rotifers, displaying high ecological risks to aquatic ecosystems.

Source apportionment of soil heavy metals with PMF model and Pb isotopes in an intermountain basin of Tianshan Mountains, China.

A boom in tourism may lead to the enrichment in heavy metals (HMs) in soils. Contamination with HMs poses a significant threat to the security of the soil environment. In this study, topsoil samples were collected from a tourist area of Sayram Lake, and the concentrations of HMs (Cr, Cu, Ni, Pb, Zn and Cd) were determined. With contamination and eco-risk assessment models, correlation analysis, Pb isotope ratios, redundancy analysis and positive matrix factorization (PMF) model, the risks and sources of HMs in the soil were studied. The Igeo results suggested that Cd was the primary pollutant in the tourist area of Sayram Lake. The potential ecological risk index (PERI) showed that the study area was at low risk, and the pollution load index (PLI) indicated that the study area had a moderate contamination level. Qualitative and quantitative analyses apportioned three sources of HMs, namely, natural sources (38.5%), traffic sources (27.2%) and mixed sources (tourist waste and atmospheric deposition) (34.3%). Redundancy analysis results showed that the HMs content was related to SiO2, Al2O3, TiO2, P2O5, MnO, K2O, Fe2O3 and SOC, and heavy metals tended to be stored in soil particles of grain sizes < 32 µm. These findings are expected to provide useful insights into the source identification of HMs in the soils of mountain tourism areas and provide a scientific decision-making basis for sustainable tourism development and for the assessment of ecological service values in the Tianshan Mountains.

The Relationship between Brachionus calyciflorus-Associated Bacterial and Bacterioplankton Communities in a Subtropical Freshwater Lake.

Zooplankton bodies are organic-rich micro-environments that support fast bacterial growth. Therefore, the abundance of zooplankton-associated bacteria is much higher than that of free-living bacteria, which has profound effects on the nutrient cycling of freshwater ecosystems. However, a detailed analysis of associated bacteria is still less known, especially the relationship between those bacteria and bacterioplankton. In this study, we analyzed the relationships between Brachionus calyciflorus-associated bacterial and bacterioplankton communities in freshwater using high-throughput sequencing. The results indicated that there were significant differences between the two bacterial communities, with only 29.47% sharing OTUs. The alpha diversity of the bacterioplankton community was significantly higher than that of B. calyciflorus-associated bacteria. PCoA analysis showed that the bacterioplankton community gathered deeply, while the B. calyciflorus-associated bacterial community was far away from the whole bacterioplankton community, and the distribution was relatively discrete. CCA analysis suggested that many environmental factors (T, DO, pH, TP, PO43-, NH4+, and NO3-) regulated the community composition of B. calyciflorus-associated bacteria, but the explanatory degree of variability was only 37.80%. High-throughput sequencing revealed that Raoultella and Delftia in Proteobacteria were the dominant genus in the B. calyciflorus-associated bacterial community, and closely related to the biodegradation function. Moreover, several abundant bacterial members participating in carbon and nitrogen cycles were found in the associated bacterial community by network analysis. Predictive results from FAPROTAX showed that the predominant biogeochemical cycle functions of the B. calyciflorus-associated bacterial community were plastic degradation, chemoheterotrophy, and aerobic chemoheterotrophy. Overall, our study expands the current understanding of zooplankton-bacteria interaction and promotes the combination of two different research fields.

Down-regulating Nrf2 by tangeretin reverses multiple drug resistance to both chemotherapy and EGFR tyrosine kinase inhibitors in lung cancer.

Multiple drug resistance (MDR) is the major obstacle for both chemotherapy and molecular-targeted therapy for cancer, which is mainly caused by overexpression of ABC transporters or genetic mutation of drug targets. Based on previous studies, we hypothesized that ROS/Nrf2 is the common target for overcoming acquired drug resistance to both targeted therapy and chemotherapy treatments. In this study, we firstly proved that the levels of ROS and Nrf2 were remarkably up-regulated in both H1975 (Gefitinib-resistant lung cancer cells with T790M) and A549/T (paclitaxel-resistant) cells, which is consistent with the clinical database analysis results of lung cancer patients that Nrf2 expression level is negatively related to survival rate. Nrf2 Knockdown with siRNA or tangeretin (TG, a flavonoid isolated from citrus peels) inhibited the MDR cell growth by suppressing the Nrf2 pathway, and efficiently enhanced the anti-tumor effects of paclitaxel and AZD9291 (the third generation of TKI) in A549/T or H1975, respectively. Moreover, TG sensitized A549/T cells-derived xenografts to paclitaxel via inhibiting Nrf2 and its downstream target P-gp, leading to an increased paclitaxel concentration in tumors. Collectively, targeting Nrf2 to enhance ROS may be a common target for overcoming the acquired drug resistance and enhancing the therapeutic effects of chemotherapy and molecular-targeted therapy.

Divergent leaf and fine root "pressure-volume relationships" across habitats with varying water availability.

Fine roots and leaves, the direct interfaces of plants with their external environment along the soil-plant-atmosphere continuum, are at the front line to ensure plant adaptation to their growing habitat. This study aimed to compare the vulnerability to water deficit of fine roots and leaves of woody species from karst and mangrove forests-two water-stressed habitats-against that of timber and ornamental woody species grown in a well-watered common garden. Thus, pressure-volume curves in both organs of 37 species (about 12 species from each habitat) were constructed. Fine roots wilted at a less negative water potential than leaves in 32 species and before branch xylem lost 50% of its hydraulic conductivity in the 17 species with available data on branch xylem embolism resistance. Thus, turgor loss in fine roots can act as a hydraulic fuse mechanism against water stress. Mangroves had higher leaf resistance against wilting and lower leaf-specific area than the karst and common garden plants. Their fine roots had high specific root lengths (SRL) and high capacitance to buffer water stress. Karst species had high leaf bulk modulus, low leaf capacitance, and delayed fine root wilting. This study showed the general contribution of fine roots to the protection of the whole plant against underground water stress. Our findings highlight the importance of water storage in the leaves and fine roots of mangrove species and high tolerance to water deficit in the leaves of mangrove species and the fine roots of some karst species.

The combination of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair alleviated inflammation in liver fibrosis.

Objective: To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair (LFP) in carbon tetrachloride (CCl4)-induced rat liver fibrosis. Methods: The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.8.0 and the STRING database, and potential protein functions were analyzed using bioinformatics analysis. Based on these analyses, we determined the main active ingredients of LFP and evaluated their effects in a CCl4-induced rat liver fibrosis model. Serum biochemical indices were measured using commercial kits, hepatocyte tissue damage and collagen deposition were evaluated by histopathological studies, and myofibroblast activation and inflammation were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. High-performance liquid chromatography-mass spectrometry was performed to determine the levels of homocysteine, reduced glutathione, and oxidized glutathione, which are involved in inflammation and oxidative stress. Results: The main active components of LFP were quercetin, kaempferol, and luteolin, and its main targets were α-smooth muscle actin, cyclooxygenase-2, formyl-peptide receptor-2, prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator-2, interleukinß, tumor necrosis factor α, CXC motif chemokine ligand 14, and transforming growth factor ß1. A combination of quercetin, kaempferol, and luteolin alleviated the symptoms of liver fibrosis. Conclusion: The results of this study support the role of LFP in the treatment of liver fibrosis, and reveal that LFP reduces collagen formation, inflammation, and oxidative stress. This study suggests a potential mechanism of action of LFP in the treatment of liver fibrosis.

Bioaccumulation and biomagnification effects of nano-TiO2 in the aquatic food chain.

The increasing production of nano-TiO2 has attracted extensive concerns about the ecological consequence and health risk of these compounds in natural ecosystem. However, little is known about its toxicity on zooplankton, especially its possibility to access to the food chain via dietary exposure. To address this concern, the toxic and cumulative effects of nano-TiO2 on an aquatic food chain were explored through two trophic levels independently or jointly including producer and consumer. The results revealed that exposure to suspensions of nanomaterials had negative effects on both producers and consumers. Specifically, nanoparticles reduced the density of algal cells in a concentration-dependent way, and hatching life expectancy, average lifespan, net reproductive rate, and population intrinsic growth rate of rotifers decreased significantly with the concentration of nanomaterials increased (P < 0.05). Notably, nanoparticles accumulated in algal cells and were transferred to consumers through dietary exposure. Biomagnification of nano-TiO2 was observed in this simplified food chain, as many of the biomagnification factor (BMF) values in this study were >1. Exposure concentration, exposure time and their interactions play a strong part in the accumulation of nanoparticles in algae and rotifers. Overall, the present findings confirmed that nano-TiO2 was deleterious to plankton, posing a significant environmental threat to aquatic ecosystems. Graphical abstract.

Clinical Outcome Discrimination in Pediatric ARDS by Chest Radiograph Severity Scoring.

Background: There is no accurate radiological measurement to estimate the severity of pediatrics acute respiratory distress syndrome (PARDS). We validated the effectiveness of an adult radiographic assessment of lung edema (RALE) score in PARDS. Aim: To assess the severity and prognosis of PARDS based on a chest radiograph (CXR) RALE scoring method. Methods: Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria were used to diagnose PARDS. General demographics, pulmonary complications, and 28-day mortality of the patients were recorded. Subgroups were compared by prognosis (survive and death) and etiology (infection and noninfection). Two observers calculated RALE independently. Each quadrant of CXR was scored by consolidation scores 0 (none alveolar opacity), 1 (extent <25%), 2 (extent 25%-50%), 3 (50%-75%), and 4 (>75%) and density scores 1 (hazy), 2 (moderate), and 3 (dense). Quadrant score equals consolidation score times density score. Total score equals to the sum of four quadrants scores. The ROC curve and survival curve were established, and the optimal cutoff score for discrimination prognosis was set. Results: 116 PARDS (72 boys and 44 girls) and 463 CXRs were enrolled. The median age was 25 months (5 months, 60.8 months) and with a mortality of 37.9% (44/116). The agreement between two independent observers was excellent (ICC = 0.98, 95% CI: 0.97-0.99). Day 3 score was independently associated with better survival (p < 0.001). The area under the curve of ROC was 0.773 (95% CI: 0.709-0.838). The cutoff score was 21 (sensitivity 71.7%, specificity 76.5%), and the hazard ratio (HR) was 9.268 (95% CI: 1.257-68.320). The pulmonary complication showed an HR of 3.678 (95% CI: 1.174-11.521) for the discrimination. Conclusion: CXR RALE score can be used in PARDS for discriminating the prognosis and has a better agreement among radiologist and pediatrician. PARDS with pulmonary complications, day 3 score whether greater than 21 points, have a better predictive effectiveness.

Comparison of survival, acute toxicities, and dose-volume parameters between intensity-modulated radiotherapy with or without internal target volume delineation method and three-dimensional conformal radiotherapy in cervical cancer patients: A retrospective and propensity score-matched analysis.

BACKGROUND: To evaluate whether the use of the internal target volume (ITV) delineation method improves the performance of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in terms of survival, acute toxicities, and dose-volume parameters. METHODS: A total number of 477 cervical cancer patients who received concurrent chemoradiotherapy (CCRT) from January 2012 to December 2016 were retrospectively analyzed. They were divided into four groups: the non-ITV (N-ITV) + IMRT, ITV + IMRT, N-ITV + 3DCRT, and ITV + 3DCRT groups, with 76, 41, 327, and 33 patients, respectively. Survival analysis was performed with the Kaplan-Meier and the log-rank tests, and acute toxicity analysis was performed with the chi-squared test and the binary logistic regression test. Using the propensity score matching (PSM) method, 92 patients were matched among the four groups, and their dose-volume parameters were assessed with the Kruskal-Wallis method. RESULTS: The median follow-up time was 49 months (1-119) for overall survival (OS). The 5-year OS rate was 66.4%. The ITV delineation method was an independent prognostic factor for OS (HR [95% CI]: 0.52 [0.27, 0.98], p = 0.044) and progression-free survival (PFS) (HR [95% CI]: 0.59 [0.36, 0.99], p = 0.045). The ITV + IMRT group had the lowest incidence rate (22%) and the N-ITV + IMRT group had the highest incidence rate of grade ≥3 hematological toxicity (HT) (46.1%) among the four groups. The pelvic bone marrow relative V10, V20, and V30 in the N-ITV + IMRT group was higher than those in the ITV + IMRT and N-ITV + 3DCRT groups (p < 0.05). CONCLUSIONS: The use of ITV for IMRT treatment planning was associated with improved overall survival and progression-free survival, with lower HT rate.

Evaluation of lipid metabolism imbalance in HIV-infected patients with metabolic disorders using high-performance liquid chromatography-tandem mass spectrometry.

Human immunodeficiency virus (HIV) infection and highly active antiretroviral therapy use are associated with the disruption of lipid and glucose metabolism. Herein, a sensitive and robust high-performance liquid chromatography-tandem mass spectrometry method for the quantitation of lysophosphatidylcholines (LPCs) and acylcarnitines (ACs) in human blood serum was developed and validated to investigate them as markers of metabolic disorders in HIV-infected patients. Under optimal extraction and detection conditions, the lower limits of quantification reached 5 ng/mL (LPCs) and 0.1 ng/mL (ACs), and precision and accuracy for both intra- and inter-day analyses were generally below 15%. Serum samples were stable for at least six months when stored at - 80 °C and for at least 12 h when stored at 4 °C or 25 °C. We investigated inter-group differences and associations between the biomarkers and observed a particular volatilitytrend of LPCs and ACs for HIV-infected patients with metabolic disorders. Thus, the developed method can be used for the rapid and sensitive quantitation of LPCs and ACs in vivo to further appraise the process of HIV infection, evaluate interveningmeasures, conduct mechanistic investigations, and further study the utility of LPCs and ACs as biomarkers of HIV infection coupled with metabolic disorders.

Quercetin 7-rhamnoside protects against alpha-naphthylisothiocyanate (ANIT)-induced in cholestatic hepatitis rats by improving biliary excretion and inhibiting inflammatory responses.

Objective: To explore the pharmacological effects and molecular mechanism of quercetin 7-rhamnoside (Q7R) in the treatment of cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT). Methods: ANIT-induced cholestatic hepatitis rat model was used to investigate the hepatoprotective effects of three different doses of Q7R (1.25 mg/kg; 2.5 mg/kg; 5 mg/kg). Serum biochemical indices were detected using commercial kits. H&E and masson staining were used to observe hepatic tissue damage and collagen deposition in hepatocytes. The metabolism of bile acid-related substances was detected via HPLC-MS/MS by 5-(diisopropylamino) amylamine (DIAAA) derivative method. Hepatocyte injury, cholestasis, and inflammation were detected at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively. Results: Q7R can decrease the level of CYP7A1, and increase FXR, CYP27A1 so then improving abnormal bile acid secretion. Furthermore, Q7R can also ameliorating inflammation by reduce TNF-α, IL-1ß, PTGS1, PTGS2, NCOA2, NF-κB level. Therefore, Q7R had an effective therapeutic effect on ANIT-induced cholestatic hepatitis, improving abnormal bile acid secretion, and inhibiting inflammatory responses. Conclusion: The results demonstrated that Q7R treat cholestatic hepatitis by regulating bile acid secretion and alleviating inflammation.