Interventional effects of Pueraria oral liquid on T2DM rats and metabolomics analysis.

Pueraria lobata, commonly known as kudzu, is a medicinal and food plant widely used in the food, health food, and pharmaceutical industries. It has clinical pharmacological effects, including hypoglycemic, antiinflammatory, and antioxidant effects. However, its mechanism of hypoglycemic effect on type 2 diabetes mellitus (T2DM) has not yet been elucidated. In this study, we prepared a Pueraria lobata oral liquid (POL) and conducted a comparative study in a T2DM rat model to evaluate the hypoglycemic effect of different doses of Pueraria lobata oral liquid. Our objective was to investigate the hypoglycemic effect of Puerarin on T2DM rats and understand its mechanism from the perspective of metabolomics. In this study, we assessed the hypoglycemic effect of POL through measurements of FBG, fasting glucose tolerance test, plasma lipids, and liver injury levels. Furthermore, we examined the mechanism of action of POL using hepatic metabolomics. The study's findings demonstrated that POL intervention led to improvements in weight loss, blood glucose, insulin, and lipid levels in T2DM rats, while also providing a protective effect on the liver. Finally, POL significantly affected the types and amounts of hepatic metabolites enriched in metabolic pathways, providing an important basis for revealing the molecular mechanism of Pueraria lobata intervention in T2DM rats. These findings indicate that POL may regulate insulin levels, reduce liver damage, and improve metabolic uptake in the liver. This provides direction for new applications and research on Pueraria lobata to prevent or improve T2DM.

[Effects of Application of Different Organic Materials on Phosphorus Accumulation and Transformation in Vegetable Fields].

Presently, the improvement of soil organic matter is the basis to ensure food security, but the accumulation and transformation characteristics of soil phosphorus (P) as affected by organic matter remain unclear. The accumulation, transformation, and migration characteristics of soil P in different soil layers of vegetable fields were researched under the application of organic materials. Six treatments were set up in the experiment:control (no fertilization), traditional fertilizer application by farmers, biochar, chicken manure, food waste, and straw application. Available phosphorus (Olsen-P), water-soluble phosphorus (CaCl2-P) content, soil phosphorus forms, soil organic matter (SOM), and pH were determined during the pepper harvest period. In the 0-5 cm and 5-10 cm soil layers, the available phosphorus content of traditional fertilization of farmers was higher, and the available phosphorus content of the four organic materials was in the order of straw > biochar > chicken manure > food waste. Compared to that with food waste, the straw and biochar treatments increased soil available phosphorus by 59.6%-67.3% and 29.1%-36.9%, respectively. The straw treatment could easily enhance the soil labile P pool, and soil labile P in the 0-5 cm soil layer increased by 47.3% and 35.1% compared with that under the chicken manure and food waste treatments, respectively. With the increase in soil depth, the proportion of available phosphorus in the chicken manure treatment decreased the least, and available phosphorus of the 20-30 cm soil layer accounted for 55.9% of the topsoil layer but only accounted for 16.0%-34.0% under treatment with the other three materials. Compared with that under the traditional fertilization of farmers, the pH significantly increased by 0.18-0.36 units after the application of organic fertilizer, and the pH of the chicken manure and food waste treatments was significantly higher than that of biochar and straw (P < 0.05). SOM content under the biochar treatment significantly increased by 7.7%-17.6% compared to that under the other three organic materials. Among the four organic materials, the straw treatment boosted the labile P pool the most, which was conducive to the rapid increase in plant-available P. Phosphorus was most likely to migrate downward under the chicken manure treatment. In the field management based on soil fertility enhancement, the application of biochar could not only improve soil pH and SOM but also avoid excessive accumulation of phosphorus in the surface layer, which decreases environmental risks.

The compensatory increase of Gli-similar 3 inhibited neuronal apoptosis through regulating Mps one binder kinase activator 1b (MOB1b): a possible strategy for the functional recovery after spinal cord injury.

Spinal cord injury (SCI) is a devastating disease characterized by neuronal apoptosis. Gli-similar 3 (GLIS3), a transcriptional factor, was involved in cell apoptosis and associated with the transcription of downstream target genes related to neuronal function. However, the function of GLIS3 in SCI remains unknown. Therefore, we used the mouse model of SCI to explore the role of GLIS3 in SCI. The results showed that GLIS3 expression was significantly increased in spinal cord tissues of SCI mice, and GLIS3 overexpression promoted the functional recovery, reserved histological changes, and inhibited neuronal apoptosis after SCI. Through online tools, the potential target genes of GLIS3 were analyzed and we found that Mps one binder kinase activator 1b (Mob1b) had a strong association with SCI among these genes. MOB1b is a core component of Hippo signaling pathway, which was reported to inhibit cell apoptosis. MOB1b expression was significantly increased in mice at 7 days post-SCI and GLIS3 overexpression further increased its expression. Dual-luciferase reporter assay revealed that GLIS3 bound to the promoter of Mob1b and promoted its transcription. In conclusion, our findings reveal that the compensatory increase of GLIS3 promotes functional recovery after SCI through inhibiting neuronal apoptosis by transcriptionally regulating MOB1b. Our study provides a novel target for functional recovery after SCI.

The risk of concurrent malignancies in patients with multiple endocrine neoplasia type 1: insights into clinical characteristics of those with multiple endocrine neoplasia type 1.

OBJECTIVE: Summarize and analyze the characteristics of patients with Multiple Endocrine Neoplasia type 1 (MEN-1) who were diagnosed with malignant tumors that do not belong to MEN-1 components. METHODS: Clinical data from patients with MEN-1 who visited Peking Union Medical College Hospital between April 2012 and April 2022 were collected. We compared the clinical characteristics of patients with malignant tumors outside of their MEN-1 components to those without additional tumors. MEN-1 gene testing was performed on most of these patients using Sanger sequencing, whole-exome sequencing, or MLPA. RESULTS: A total of 221 MEN-1 patients were diagnosed, of which 23 (10.40%) were found to have malignant tumors that did not belong to MEN-1 components, including papillary thyroid carcinoma (PTC) (4.52%), breast cancer (1.81%), urologic neoplasms (1.35%), primary hepatic carcinoma (PCC) (0.09%), meningeal sarcoma (0.05%), glioblastoma (0.05%), cervical cancer (0.05%), and lung carcinoma (0.05%). MEN-1 gene mutations were identified in 11 patients, including missense mutations, frameshift mutations, and splice mutations. The prevalence of each endocrine neoplasm, particularly gastroenteropancreatic neuroendocrine tumor, was higher in MEN-1 patients with other malignant tumors compared to MEN-1 patients without malignant tumors. CONCLUSION: Our retrospective study revealed a higher incidence of non-MEN-1 component malignant tumors in MEN-1 patients, especially breast cancer, PTC, and urologic neoplasms. These patients also exhibit more severe clinical phenotypes of MEN-1.

Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets.

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet ß-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.

Diagnosis, Genetics, and Management of 24 Patients With Cardiac Paragangliomas: Experience From a Single Center.

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

Magnetic resonance imaging of knees: a novel approach to predict recombinant human growth hormone therapy response in short-stature children in late puberty.

BACKGROUND: There is no appropriate tool to predict recombinant human growth hormone (rhGH) response before therapy initiation in short-stature children in late puberty. The current study aimed to explore the associations between magnetic resonance imaging (MRI) stages of the knee growth plates and rhGH response in short-stature children in late puberty. METHODS: In this prospective cohort study, short-stature children in late puberty were treated with rhGH and followed up for 6 months. We proposed a novel knee MRI staging system according to the growth plate states of distal femurs or proximal tibias and divided the participants into three groups: unclosed growth plate group, marginally closed growth plate group, and nearly closed growth plate group. The primary outcomes were height gain and growth velocity (GV), which were assessed three months later. RESULTS: Fifty participants were enrolled, including 23 boys and 27 girls. GV and height gain after 6 months of rhGH therapy decreased successively in the three groups with an increased degree of growth plate fusion, especially when grouped by proximal tibias (GV1-3 mon from 9.38 to 6.08 to 4.56 cm/year, GV4-6 mon from 6.75 to 4.92 to 3.25 cm/year, and height gain from 4.03 to 2.75 to 1.95 cm, all P < 0.001). Moreover, the MRI stages of growth plates independently served as a significant variable for GV and height gain after therapy, especially when grouped by proximal tibias (all P < 0.01). CONCLUSION: The MRI staging method is expected to be an effective tool for predicting rhGH response before therapy initiation in short-stature children in late puberty.

Blood Lipid Disorders in Post-Operative Craniopharyngioma Children and Adolescents and the Improvement with Recombinant Human Growth Hormone Replacement.

Context: The high prevalence of hypothalamic obesity (HO) and dyslipidemia in individuals with craniopharyngioma (CP) following surgery is a cause for increasing concern. However, few studies have explored the lipid profile in pediatric CP patients, with inconsistent findings. In addition, the role of recombinant human growth hormone (rhGH) replacement remains unclear in these patients. Objective: To compare the blood lipid profile among post-operative craniopharyngioma children and adolescents with that among healthy controls and to reveal the effects of rhGH replacement. Methods: Data of 79 post-operative craniopharyngioma children and adolescents in our center were retrospectively collected. Sixty patients underwent rhGH replacement during the follow-ups. We selected 36 patients who received rhGH replacement therapy, while 20 patients received rhGH replacement for at least 1 year and had complete lipid data before and after treatment and compared them with 19 patients who did not receive rhGH replacement therapy. Results: Craniopharyngioma patients had higher total cholesterol (TC) (5.17 vs 3.77 mmol/L), triglyceride (TG) (1.51 vs 0.73 mmol/L), and low-density lipoprotein cholesterol (LDL-C) (3.14 vs 2.10 mmol/L), and lower high-density lipoprotein cholesterol (HDL-C) (1.06 vs 1.39 mmol/L) than controls (all p < 0.001). The lipid profile of obese and non-obese patients was not significantly different. After rhGH replacement, TC was 0.90 mmol/L lower (p = 0.002) and LDL-C was 0.73 mmol/L lower (p = 0.010) than baseline. Although the baseline LDL-C was higher, patients with rhGH replacement had lower LDL-C (-0.73 mmol/L adjusted for age and sex, p = 0.045) after the initiation of replacement compared with patients without rhGH replacement. Conclusion: The lipid profile of obese and non-obese children and adolescents with craniopharyngioma was unfavorable, and rhGH replacement could improve their lipid profile.

Two New C18 -Diterpenoid Alkaloids from Aconitum leucostomum Worosch.

Two new lappaconitine-type C18 -diterpenoid alkaloids, named as leucostosines C (1) and D (2), together with six known compounds (3-8), were isolated from the roots of Aconitum leucostomum Worosch. Their structures were elucidated by various spectroscopic analyses, including IR, HR-ESI-MS, NMR spectra and X-ray experiments. Leucostosine C is the first diterpenoid alkaloid bearing the 7-amino group. The isolated compounds were tested for the acetylcholinesterase (AChE) inhibitory effect and neuroprotective activity, none of them showed significant activities.

Research Advances in Pharmacology, Safety, and Clinical Applications of Yunnan Baiyao, a Traditional Chinese Medicine Formula.

Ethnopharmacology relevance: Yunnan Baiyao (YNBY), a traditional Chinese medicine formulae, has some significant properties including activating blood circulation to dissipate blood stasis (Huo-Xue-Hua-Yu), eliminating swelling and alleviating pain (Xiao-Zhong-Zhi-Tong), and eliminating necrotic tissues and promoting granulation (Qu-Fu-Sheng-Ji). Aim of this study: This paper intends to provide a comprehensive and critical analysis of studies on YNBY, proposing new possible therapeutic directions of this formula. Materials and methods: Relevant data on YNBY were retrieved from available databases and a hand-search by searching the keywords such as "Yunnan Baiyao," "pharmacology," "toxicity," and "clinical applications." Results: Traditionally, YNBY has been used to cure hemorrhage, bruises, swelling, and pain caused by injuries in the Chinese folk. Modern pharmacological studies show that YNBY possesses pharmacological activities including hemostasis, invigorating the circulation of blood, wound healing, anti-inflammation, analgesia, antibiosis, infection prevention, and other effects. Toxicological studies demonstrate that YNBY has a certain toxicology, which is mainly caused by Aconitum alkaloids from Cao-wu (CW, Aconiti Kusnezoffii Radix). The developmental non-toxic reaction dose (NOAEL) of YNBY for embryos and fetuses is 0.5 g/kg in rats. In addition, the NOAEL for fertility and early embryo development toxicity is 4.0 g/kg in rats. Clinical trials have confirmed the safety of YNBY in a large number of patients, and adverse drug reactions (ADRs) such as abdominal pain, diarrhea, allergy, and others in very few people. YNBY is routinely used in clinic to cure bleeding, pain, swelling, upper digestive tract ulcer, postoperative wound, arthritis, mouth ulcers, ulcerative colitis, etc. Conclusions: Hemostasis is a conspicuous effect of YNBY. Except for this effect, analgesia and anti-infection may be new research directions of this formula. In addition, the in vitro and in vivo pharmacology and mechanisms of action of YNBY are encouraged as well as the pharmacokinetics of this formulae. Furthermore, the material basis of the pharmacological effects of YNBY also needs clear identification.

[Occurrence Characteristics and Health Risk Assessment of Endocrine Disrupting Chemicals in Groundwater in Wuxi-Changzhou].

The concentrations of 22 endocrine disrupting chemicals, including 4 categories of sex hormones, progesterones, glucocorticoids, and phenolic hormones, in groundwater of Wuxi-Changzhou were analyzed using solid-phase extraction and ultra-performance liquid chromatography tandem mass spectrometry. The results indicated that 20 EDCs were detected, among which bisphenol A (BPA), estrone (E1), estradiol (E2), and 17α-ethinyl estradiol (EE2) were the main components with detection ratios greater than 90%, followed by estriol (E3) and methyl-prednisolonel (Meprednl), which had detection rates 67.7% and 48.4%, respectively. The average concentration of BPA was the highest (4.95 ng·L-1), followed by that of Meprednl, E2, prednisolone (Prednl), testosterone propionate (TES-pro), and megestrol-acetate (MA; 2.84, 0.71, 0.64, 0.58, and 0.53 ng·L-1, respectively). The total concentration in each site ranged from 0.38 to 147.35 ng·L-1. The sites with higher concentration were mainly distributed in the Xinbei District, Liyang City, and the Zhonglou District of Changzhou City. The potential sources were analyzed by a principal component analysis (PCA) combining the point sources near sample sites. The results showed that domestic sewage, aquaculture, and industrial wastewater were the main sources, following by medical wastewater. A non-carcinogenic risk assessment showed a low risk of EDCs in the groundwater of the study area, and the risk of drinking water was greater than that of skin exposure. EE2 had the highest non-carcinogenic risk and is suggested to be monitored in priority.

Fully automated identification and quantification of five polar pesticides in groundwater by isotope dilution-online solid phase extraction coupled with high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry.

A fully automated method for identification and quantification of five polar pesticides in groundwater by isotope dilution-online solid-phase extraction (SPE) coupled with high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry was developed. After one step of filtration, an aliquot of a 7.5-ml water sample was automatedly preconcentrated and purified on a turbulent Cyclone SPE column. The analytes were eluted in backflush mode, then separated on an analytical column and acquired by full MS/dd-MS2 scan in negative and positive ions mode. The major parameters for sample loading, cleanup, and elution were optimized in detail. Preconcentration and ionization efficiency were highly improved by using 0.1% acid solution in the mobile phase. The method provided good linearity of calibration coefficients (R2 > 0.995), sensitive method limits of detection (0.5-10.0 ng/L), accurate mass spectra (within 5 ppm error), satisfactory matrix spiking recoveries (98.4% to 109%), and high precision (intraday/interday relative standard deviations 1.57-8.90%). The method was successfully applied to analyze large batch groundwater of National Groundwater Monitoring Project and suspect screening of potential pesticides in groundwater. The study provided a practical alternative for a simple, robust, sensitive, and accurate identification and qualification of five polar pesticides in groundwater.

Identification of U-shaped curve relation between proneurotensin and risk of coronary artery disease (CAD) in patients with premature CAD.

BACKGROUND AND AIMS: Neurotensin (NT) is a gut hormone with broad effects on the cardiovascular system. Recent data suggested that circulating proneurotensin (pro-NT)-the stable precursor fragment of NT-could independently predict cardiovascular artery disease (CAD) development. However, serum pro-NT levels in patients with premature cardiovascular artery disease (PCAD) are still unknown. This study aims to determine serum pro-NT levels in patients with PCAD and investigate its relationship with PCAD risk. METHODS AND RESULTS: A total of 490 subjects, including 364 with PCAD and 126 without PCAD (NPCAD), and 182 controls were enrolled in the study. Data of baseline clinical parameters and biochemical variables were collected. Serum pro-NT levels were measured by ELISA. Serum pro-NT levels were higher in patients with PCAD than in controls (59.42 ± 66.66 vs. 38.07 ± 48.48 pg/mL, P < 0.05), especially in patients with BMI<25 kg/m2. Serum pro-NT levels were independently related to PCAD (ß = 0.349, P < 0.001), and the association revealed a U-shaped curve characteristic between pro-NT tertiles and CAD risk in patients with premature CAD and controls. Subjects with low and high tertiles of pro-NT levels had 1.79-fold and 2.23-fold higher risks of PCAD, respectively, than subjects with median pro-NT levels (P < 0.05). After adjusting for age, gender, and BMI in Model 1 and other confounders in Model 2 and Model 3, the U-shaped relationship remained significant. CONCLUSION: Serum pro-NT levels were significantly increased in patients with PCAD. The association between pro-NT levels and PCAD risk presents a U-shaped curve characteristic, which demonstrated that subjects with lower and higher pro-NT levels both were more likely to have PCAD.

Comparative Proteome Analysis of Epicardial and Subcutaneous Adipose Tissues from Patients with or without Coronary Artery Disease.

BACKGROUND AND AIMS: Owing to its unique anatomical structure and metabolism, epicardial adipose tissue (EAT) has attracted amount of attention in coronary artery disease (CAD) research. Here, we analyzed differences in proteome composition in epicardial (EAT) and subcutaneous adipose tissues (SAT) from patients with or without CAD. METHODS: EAT and SAT samples were collected from 6 CAD patients and 6 non-CAD patients. Isobaric Tagging for Relative and Absolute Quantitation (iTRAQ) analysis combined with liquid chromatography tandem-mass spectrometry (LC-MS/MS) was performed to identify the differentially expressed proteins. RESULTS: In total, 2348 proteins expressed in EAT and 2347 proteins expressed in SAT were separately identified. 385 differentially expressed proteins were found in EAT and 210 proteins were found in SAT in CAD patients compared to non-CAD patients. Many proteins differentially expressed in EAT of CAD patients were involved in biological functions associated with CAD development such as cell-to-cell signaling and interaction, inflammatory response, and lipid metabolism. Differential expressions of proteins (MMP9, S100A9, and clusterin) in EAT or SAT were involved in several signaling pathways such as mitochondrial dysfunction, acute phase inflammation, and LXR/RXR activation, which was confirmed by western blotting, and similar results were obtained. CONCLUSIONS: The largest profiles of differentially expressed proteins in EAT and SAT between CAD patients and non-CAD patients were identified. The significant signal pathways, mitochondrial dysfunction, and LXR/RXR activation, which differential proteins were involved in, were firstly found to play roles in EAT of CAD patients, and clusterin was firstly found to be upregulated in EAT of CAD patients.

Clinical characteristics of non-alcoholic fatty liver disease in Chinese adult hypopituitary patients.

BACKGROUND: Patients with hypothalamic-pituitary disease have the feature of central obesity, insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease (NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients. AIM: To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients. METHODS: Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospital between August 2012 and April 2018. According to abdominal ultrasonography, these patients were divided into an NAFLD (-) group and an NAFLD (+) group, and the latter was further divided into an NAFLD group and a cirrhotic group. The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed. RESULTS: A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43 (87.0%) of these patients exhibited growth hormone (GH) deficiency, and 39 (78.3%) had diabetes insipidus. A total of 27 (54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2O and 151.0 mmol/L, respectively, which were significantly higher than those of the NAFLD patients (P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index (BMI) and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD (P = 0.011 and 0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI (r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD. CONCLUSION: NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.

Antioxidant defence system is responsible for the toxicological interactions of mixtures: A case study on PFOS and PFOA in Daphnia magna.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two types of perfluorinated compounds (PFCs) frequently studied in recent years due to their potential for bioaccumulation and toxicity to humans. Usually, PFCs can co-exist in various environment. Therefore, over- or under-estimated risk assessments would result if antagonism or synergism occurred in mixture toxicity. In the present study, the acute and chronic toxicities of single and mixtures of PFOA and PFOS to Daphnia magna were investigated. PFOS was more toxic than PFOA, both in 48-h acute toxicity and 21-d chronic toxicity. In acute toxicity tests, mixture toxicities showed strong synergistic effects on mortality. The experimental EC50 of the mixture is 4.44 × 10-5 mol/L, whereas the predicted EC50 is 8.19 × 10-5 mol/L by Concentration Addition Model and 9.73 × 10-5 mol/L by Independent Action Model. In chronic toxicity tests, synergistic effects were also found in the aspects of offspring. The offspring rate is reduced significantly to 39.8% at the 9.61 × 10-7 mol/L of mixture, while, PFOS and PFOA do not have effects when they are tested individually at corresponding concentrations. To explore the potential mechanism of the synergistic effect, the interactions between PFCs and proteins, including acetylcholinesterase, superoxide dismutase, catalase, ecdysone receptor and glutathione-S-transferase, were investigated by the Molecular Docking. The docking results revealed that the driving forces for the binding of PFCs with proteins were predominantly hydrophobic and hydrogen-bonding interactions. Based on the binding models, we deduced that the potential mechanism of synergism is that PFOS and PFOA have similar binding modes with catalase and have different binding modes with superoxide dismutase. Overall, these data provide experimental evidence that there is strong synergism in acute and chronic toxicity of mixtures to D. magna and demonstrate that molecular structure of some components of the antioxidant defence system contributes to the synergistic interaction.

[Severe Hyperthyroidism-Heart Failure-Severe Liver Injury:Report of One Case and Literature Review].

Severe hyperthyroidism can cause the injuries of multiple organs including heart and liver and ultimately be fatal. A 26-year-old young woman admitted to Peking Union Medical College Hospital for severe hyperthyroidism due to irregular use of anti-thyroid drugs. She had heart failure,atrial fibrillation,and severe liver damage at admission. Anti-thyroid drugs were then actively used to treat the primary disease,along with interventions to correct heart failure and control atrial fibrillation. Severe total bilirubin elevation was found during the treatment, which was resolved after the use of glucocorticoid and liver-protective therapy. The patient was regularly followed up after discharge,and the clinical manifestations were good.

Cushing's disease with pulmonary Cryptococcus neoformans infection in a single center in Beijing, China: A retrospective study and literature review.

BACKGROUND: Patients with Cushing's disease (CD) with hypercortisolism have an increased risk of opportunistic infection. However, most CD patients exposed to infections are diagnostic latency, leading to a poor prognosis. METHODS: Six patients in our hospital and an additional six patients in the literature were included in this study. Clinical information of CD patients with pulmonary Cryptococcus neoformans are reviewed. RESULTS: The average baseline total cortisol and ACTH in serum at 8 am of all the patients was 44.85 µg/dL (normal range 4.0-22.3 µg/dL) and 200.3 pg/mL (normal range 0-46 pg/mL), respectively. Lymphopenia was found in 2 out of 6 patients in our hospital. The pulmonary radiologic findings included nodules (4/12), masses with or without a cavity (5/12), infiltration (5/12), and consolidation (4/12). The diagnosis of C.neoformans was established by lung pathology results (7/12), microorganism culture (3/12), and serum cryptococcal polysaccharide antigen (4/12). Lung lobectomy was performed in two patients who had a nodule in one lung lobe. Antifungal drugs were administered, including amphotericin-B (7/12), fluconazole (4/12), flucytosine (2/12) and liposomal amphotericin (1/12). Additional therapies for CD included trans-sphenoidal pituitary adenoma surgery (9/12), adrenalectomy (1/12) and ketoconazole (2/12). Seven patients survived, and five patients died. CONCLUSION: Pulmonary C.neoformans is an uncommon but fatal opportunistic infection in CD patients. Pulmonary nodules or masses should be aggressively investigated to exclude the C.neoformans among CD patients. The infiltration lesions in chest CT scan and lymphopenia are associated with poor prognosis.

Structure of a MacAB-like efflux pump from Streptococcus pneumoniae.

The spr0693-spr0694-spr0695 operon of Streptococcus pneumoniae encodes a putative ATP-binding cassette (ABC)-type efflux pump involved in the resistance of antibiotics and antimicrobial peptides. Here we report the crystal structures of Spr0694-0695 at 3.3 Å and Spr0693 at 3.0 Å resolution, revealing a MacAB-like efflux pump. The dimeric Spr0694-0695 adopts a non-canonical fold of ABC transporter, the transmembrane domain of which consists of eight tightly packed transmembrane helices with an insertion of extracellular domain between the first and second helices, whereas Spr0693 forms a nanotube channel docked onto the ABC transporter. Structural analyses combined with ATPase activity and antimicrobial susceptibility assays, enable us to propose a putative substrate-entrance tunnel with a lateral access controlled by a guard helix. Altogether, our findings provide structural insights and putative transport mechanism of a MacAB-like efflux pump in Gram-positive bacteria.