The lipid transporter Mfsd2a maintains pulmonary surfactant homeostasis.

Pulmonary surfactant is a lipoprotein complex essential for lung function, and insufficiency or altered surfactant composition is associated with major lung diseases, such as acute respiratory distress syndromes, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. Pulmonary surfactant is primarily composed of phosphatidylcholine (PC) in complex with specialized surfactant proteins and secreted by alveolar type 2 (AT2) cells. Surfactant homeostasis on the alveolar surface is balanced by the rates of synthesis and secretion with reuptake and recycling by AT2 cells, with some degradation by pulmonary macrophages and loss up the bronchial tree. However, whether phospholipid (PL) transporters exist in AT2 cells to mediate reuptake of surfactant PL remains to be identified. Here, we demonstrate that major facilitator superfamily domain containing 2a (Mfsd2a), a sodium-dependent lysophosphatidylcholine (LPC) transporter, is expressed at the apical surface of AT2 cells. A mouse model with inducible AT2 cell-specific deficiency of Mfsd2a exhibited AT2 cell hypertrophy with reduced total surfactant PL levels because of reductions in the most abundant surfactants, PC containing dipalmitic acid, and PC species containing the omega-3 fatty acid docosahexaenoic acid. These changes in surfactant levels and composition were mirrored by similar changes in the AT2 cell lipidome. Mechanistically, direct tracheal instillation of fluorescent LPC and PC probes indicated that Mfsd2a mediates the uptake of LPC generated by pulmonary phospholipase activity in the alveolar space. These studies reveal that Mfsd2a-mediated LPC uptake is quantitatively important in maintaining surfactant homeostasis and identify this lipid transporter as a physiological component of surfactant recycling.

Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study.

BACKGROUND: Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood. METHODS: LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma samples collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted samples collected from mothers at 26-28 weeks of gestation (n=752) and 4-5 years postpartum (n=650), and their offspring at birth (n=751) and 6 years of age (n=338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort (n=1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation. RESULTS: Levels of 36% of the profiled lipids were significantly higher (absolute fold change > 1.5 and Padj < 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log2FC=-2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log2FC=-0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends (R2=0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specifically associated with decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy. CONCLUSIONS: In summary, our study provides a detailed landscape of the in utero lipid environment provided by the gestating mother to the growing fetus, and the magnitude of changes in plasma lipidomic profiles from birth to early childhood. We identified the effects of adiposity on the circulating lipid levels in pregnant and non-pregnant women as well as offspring at birth and at 6 years of age. Additionally, the pediatric vs maternal overlap of the circulating lipid phenotype of obesity risk provides intergenerational insights and early opportunities to track and intervene the onset of metabolic adversities. CLINICAL TRIAL REGISTRATION: This birth cohort is a prospective observational study, which was registered on 1 July 2010 under the identifier NCT01174875 .

Discovery of potent and selective urea-based ROCK inhibitors: Exploring the inhibitor's potency and ROCK2/PKA selectivity by 3D-QSAR, molecular docking and molecular dynamics simulations.

An activity model and a selectivity model from 3D-QSAR studies were established by CoMFA and CoMSIA to explore the SAR. Then docking was used to study the binding modes between ligand and kinases (ROCK2 and PKA), and the molecular docking results were further validated by MD simulations. Computational results suggested that substitution containing positive charge attached to the middle phenyl ring, or electropositive group in urea linker was favored for both activity and ROCK2/PKA selectivity. Finally, three compounds were designed, and biological evaluation demonstrated that these molecular models were effective for guiding the design of potent and selective ROCK inhibitors.

Plasma and platelet lipidome changes in Fabry disease.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by the progressive accumulation of globotriaosylceramide (Gb3) leading to systemic manifestations such as chronic kidney disease, cardiomyopathy, and stroke. There is still a need for novel markers for improved FD screening and prognosis. Moreover, the pathological mechanisms in FD, which also include systemic inflammation and fibrosis, are not yet fully understood. METHODS: Plasma and platelets were obtained from 11 ERT (enzyme-replacement therapy)-treated symptomatic, 4 asymptomatic FD patients, and 13 healthy participants. A comprehensive targeted lipidomics analysis was conducted quantitating more than 550 lipid species. RESULTS: Sphingadiene (18:2;O2)-containing sphingolipid species, including Gb3 and galabiosylceramide (Ga2), were significantly increased in FD patients. Plasma levels of lyso-dihexosylceramides, sphingoid base 1-phosphates (S1P), and GM3 ganglioside were also altered in FD patients, as well as specific plasma ceramide ratios used in cardiovascular disease risk prediction. Gb3 did not increase in patients' platelets but displayed a high inter-individual variability in patients and healthy participants. Platelets accumulated, however, lyso-Gb3, acylcarnitines, C16:0-sphingolipids, and S1P. CONCLUSIONS: This study identified lipidome changes in plasma and platelets from FD patients, a possible involvement of platelets in FD, and potential new markers for screening and monitoring of this disease.

Nonprotein calorie supplement improves adherence to low-protein diet and exerts beneficial responses on renal function in chronic kidney disease.

OBJECTIVE: Malnutrition is common in patients with chronic kidney disease (CKD) who are on low-protein diets and is a powerful predictor of morbidity and mortality in CKD. Studies have shown that patients on low-protein diets often have difficulty meeting nutritional energy requirements. Our study evaluated the effects of a nonprotein calorie (NPC) supplement on renal function and nutritional status in patients on a low-protein diet. DESIGN: This was a prospective, randomized, open-label, controlled clinical trial. SUBJECTS: A total of 109 patients with CKD (men, 67%; mean age, 54.5 ± 13 years) with stage 3 to 4 disease were randomly assigned to the intervention group (n = 55) or the control group (n = 54). INTERVENTION: All participants received individualized dietary counseling aimed at achieving a daily protein intake of 0.6 to 0.8 g and a daily energy intake of 30 to 35 kcal/kg. The intervention group consumed a 200-kcal NPC supplement daily. The control group received dietary counseling only. MAIN OUTCOME MEASURE: The estimated glomerular filtration rate (eGFR) was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Urine protein excretion, dietary protein and energy intake, and serum levels of creatinine, urea nitrogen, cholesterol, triglycerides, and albumin were assessed at baseline, at 12 weeks, and at 24 weeks. RESULTS: Dietary protein intake and urine protein excretion levels decreased significantly in the intervention group and were significantly lower than those of the control group. In addition, serum levels of creatinine and urea nitrogen decreased significantly, and eGFR increased significantly in the intervention group compared with baseline assessments. No significant differences were observed in the control group. CONCLUSIONS: The NPC supplement improved patient adherence to the low-protein diet and reduced urine protein excretion in patients with CKD.

Lipidomic profiling of human serum enables detection of pancreatic cancer.

Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers.

Prevalence and risk factors of peripheral arterial diseases in male Chinese octogenarians and nonagenarians with hypertension.

OBJECTIVE: To investigate the prevalence and risk factors of peripheral arterial disease (PAD) in male Chinese octogenarians and nonagenarians with hypertension. METHODS: Ankle-brachial index (ABI) was measured in the noninvasive vascular laboratory for hypertensive male octogenarians and nonagenarians enrolled from outpatient and inpatient departments. The baseline conditions were investigated using standard questionnaire and by routine physical examinations. PAD was diagnosed when an ABI≤0.9 in either lower extremity. RESULTS: Totally 290 male Chinese octogenarians and nonagenarians [age: (84.61±4.20) years] with hypertension who were receiving antihypertensive therapy were enrolled in this study, among whom 9 men with missing data except age and ABI measurements. The ABI was 0.948±0.258, with the range of highest frequency of 0.91-1.30, and 106 patients were diagnosed as PAD, 182 as non-PAD, and 2 had ABI>1.3. ABI in hypertensive men with PAD were significantly lower than in those without PAD (P<0.05). On the contrary, age, blood urea nitrogen, white blood cell counts, platelets and aspartic transaminase were significantly higher in PAD patients than in non-PAD patients (all P<0.05). The prevalence of PAD in this study population were 36.5%; more specifically, it significantly differed between different subgroups when stratified by age (28.6% vs. 46.3%, below and above 85 years), with and without hypertension (27.5% vs. 40.1%), stroke (44.7% vs. 27.5%), dyslipidemia (41.4% vs. 33.3%), coronary artery disease (44.1% vs. 13.9%), and diabetes mellitus (53.7% vs. 21.8%) (all P<0.05). The prevalences of PAD in hypertensive patients treated with diuretics, calcium antagonists, beta-blocker, or angiotensin receptor antagonist were 41.4%, 36.1%, 22.4%, and 26.8%, respectively. No association was observed between the prevalence of PAD and smoking/alcohol drinking in these subjects. Multivariate analysis showed that age (OR 1.12, 95%CI 1.014-1.238), blood urea nitrogen (OR 1.15, 95%CI 1.025-1.301), aspartic transaminase (OR 1.05, 95%CI 1.005-1.089), diabetes mellitus (OR 4.02, 95%CI 1.797-9.009), coronary artery disease (OR 6.34, 95%CI 1.734-23.214) were strong risk factors of PAD. CONCLUSION: PAD is highly prevalent among aged Chinese hypertensive men, in which age, blood urea nitrogen, aspartic transaminase, diabetes mellitus, coronary artery disease may be involved in the development of this condition.

Treatment of vascular paralysis syndrome with methylene blue during kidney transplantation: one case report / 中华器官移植杂志

The report described one case of vascular paralysis syndrome during kidney transplantation to provide references for clinical practice.After intraoperative opening of kidney artery and vein, the recipient developed vascular paralysis syndrome.However, the efficacy is not obvious after dosing of norepinephrine.After an intravenous infusion of methylene blue, the recipient has a successful removal of tracheal intubation and recovered well.

41 cases of chronic obstructive pulmonary disease caused by occupational irritating chemicals / 中华劳动卫生职业病杂志

Objective: To analyze the case characteristics of Chronic obstructive pulmonary disease caused by occupational irritant chemicals (OI-COPD). To provide basis for revising its diagnostic criteria. Methods: From June to December 2021, we investigated the information of OI-COPD patients confirmed by Shandong Institute of Occupational Health and Prevention of Occupational Diseases, Guangxi Zhuang Autonomous Region Institute of Occupational Disease Prevention and Control, Qingdao Central Hospital affiliated to Qingdao University and other diagnostic institutions in the past five years, a total of 41 cases. The basic information of OI-COPD cases, occupational risk factors exposure information, medical history, smoking history and clinical symptoms were analyzed retrospectively. The measurement data were tested for normal distribution, which was described by x±s, and compared between groups by t test; Those who do not conform to the normal distribution are described by the median [M (Q(1), Q(3)) ] and analyzed by nonparametric test; The counting data were expressed in frequency and rate (% ), and the comparison between groups was tested. Results: Of the 41 cases, 33 were male and 8 were female. The age of the patient diagnosed with OI-COPD was (49.5±10.3) years old, and the minimum age was 30 years old; Among them, 8 patients had a definite long-term smoking history (more than 5 years) ; The exposure duration of occupational risk factors was (18.6±10.3) years, of which 3 patients had exposure duration of less than 5 years; The occupational risk factors leading to OI-COPD include acids and acid-forming compounds, bases, aldehydes, nitrogen oxides, chlorine and its compounds, etc. The exposure level of occupational risk factors is related to the degree of COPD airflow restriction (χ(2)=6.17, P <0.05). 18 patients with diagnosis age <50 years old were diagnosed as early-onset COPD. The incidence of respiratory symptoms in the early diagnosis COPD group was lower than that in the non-early diagnosis COPD group, and the FEV1% pred was significantly higher than that in the non-early diagnosis COPD group. The difference was statistically significant (P<0.01 ) . Conclusion: The exposure level of occupational risk factors may be the risk factor affecting the degree of COPD airflow restriction. With the increase of the exposure level of COPD patients, the proportion of respiratory symptoms will also increase accordingly.

Effect of esketamine on postoperative acute lung injury in pediatric patients undergoing living donor liver transplantation / 中华麻醉学杂志

Objective:To evaluate the effect of esketamine on postoperative acute lung injury (ALI) in pediatric patients undergoing living donor liver transplantation.Methods:Sixty pediatric patients of either sex with biliary atresia, aged 0-36 months, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, with cardiac function grade I or Ⅱ, with Child-Pugh grade B or C, undergoing living donor liver transplantation, were divided into 2 groups ( n=30 each) using a computer-generated table of random numbers: control group (group C) and esketamine group (group S). Combined intravenous-inhalational anesthesia was performed with propofol and sevoflurane in both groups, and in addition esketamine was intravenously infused continuously after induction in group S. After anesthesia induction (T 0), at 60 min after start of surgery (T 1), at 10 min after anhepatic phase (T 2), at 60 min after portal vein opening (T 3), and immediately after abdominal closure (T 4), central venous blood samples were collected for determination of the serum concentrations of Clara cell secretory protein 16, surface active protein D, soluble receptor for advanced glycation end-products, high mobility group protein B1, interleukin-1beta and tumor necrosis factor-alpha (using enzyme-linked immunosorbent assay), concentrations of malondialdehyde (using TBA method), and activity of superoxide dismutase (using hydroxylamine method). The dynamic lung compliance was recorded from T 0 to T 4. Blood samples were taken from the radial artery at T 0 and 24 h after surgery (T 5) for blood gas analysis, and oxygenation index and respiratory index were calculated. Lung ultrasound scores were recorded at 24 h before surgery and T 5. The postoperative mechanical ventilation time and duration of intensive care unit stay were recorded. The occurrence of ALI within 7 days after liver transplantation was observed. Results:Compared with group C, the serum concentrations of Clara cell secretory protein 16, surface active protein D, soluble receptor for advanced glycation end products, high mobility group protein B1, interleukin-1beta, tumor necrosis factor-alpha and malondialdehyde were significantly decreased, and the activity of superoxide dismutase was increased at T 3, 4, the oxygenation index was increased and respiratory index was decreased at T 3-T 5, lung ultrasound C score and B score were decreased at T 5, the postoperative mechanical ventilation time and duration of intensive care unit stay were shortened, and the incidence of ALI was decreased in group S ( P<0.05). Conclusions:Esketamine can alleviate postoperative ALI in pediatric patients undergoing living donor liver transplantation.

Comparison of effects of different anesthesia methods on perioperative lung injury in pediatric patients with biliary atresia undergoing living donor liver transplantation / 中华麻醉学杂志

Objective:To compare the effects of different anesthesia methods on perioperative lung injury in pediatric patients with biliary atresia undergoing living donor liver transplantation.Methods:Ninety-one American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients with biliary atresia, regardless of gender, aged 0-36 months, with cardiac function grade of Ⅰ or Ⅱ and Child-Pugh grade of B or C, undergoing elective living donor liver transplantation, were selected. According to the anesthesia method, the pediatric patients were divided into 3 groups: propofol-based anesthesia group (P group, n=30), sevoflurane-based anesthesia group (S group, n=30) and propofol-sevoflurane-based anesthesia group (PS group, n=31). Group P received intravenous infusion of 1% propofol 9-15 mg·kg -1·h -1. In group S, sevoflurane was inhaled and the end-tidal concentration was maintained at 2.6%-4.0%.In PS group, 1% propofol 9-15 mg·kg -1·h -1 was intravenously infused and sevoflurane was inhaled, maintaining an end-tidal concentration at 1.0%-2.5%. Remifentanil 0.1-1.0 μg·kg -1·min -1 was intravenously infused during operation for analgesia, and cisatracurium besylate 1-2 μg·kg -1·min -1 was intravenously infused to maintain muscle relaxation in three groups. Immediately after anesthesia induction (T 0), at 60 min after start of surgery (T 1), at 10 min of anhepatic phase (T 2), at 60 min after portal vein opening (T 3), and immediately after abdominal closure (T 4), the concentrations of serum Clara cell secretory protein 16 (CC16), surfactant protein (SP-D), soluble receptors for advanced glycation end products (s-RAGE), high mobility group protein B1 (HMGB1), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were measured using enzyme-linked immunosorbent assay method, and lung compliance (Cdyn) was simultaneously recorded. At T 0-T 4 and 24 h after surgery (T 5), the arterial blood gas analysis was performed to calculate the oxygenation index (OI) and respiratory index (RI). Lung ultrasound scores (LUS scores) were assessed at 24 h before surgery and T 5. The occurrence of pulmonary complications was recorded within 7 days after surgery. The survival was observed for 6 months after surgery. Results:There were no statistically significant differences in serum concentrations of CC16, SP-D and s-RAGE concentrations and LUS scores at different time points between group S and group P ( P>0.05). Compared with S group and P group, the serum CC16 concentrations at T 3 and s-RAGE concentrations at T 3, 4 were significantly decreased, and the C and B scores were decreased at T 5 in PS group ( P<0.05). There were no statistically significant differences in the concentrations of serum HMGB1, IL-1β and TNF-α, Cydn and incidence of ALI/ARDS, pulmonary infection, pleural effusion, and atelectasis within 7 days after surgery among the three groups( P>0.05). The 6-month survival rate was 100% in the three groups. Conclusions:Propofol-sevoflurane-based anesthesia has a better efficacy in reducing perioperative lung injury than propofol-based anesthesia and sevoflurane-based anesthesia in the perioperative period of liver transplantation.

Clinical effects of island posterior femoral composite tissue flaps in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter / 中华烧伤杂志

Objective: To explore the clinical effects of island posterior femoral composite tissue flaps in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter. Methods: The retrospective observational study was conducted. From December 2018 to December 2021, 23 patients with sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter who met the inclusion criteria were admitted to Ganzhou People's Hospital, including 16 males and 7 females, aged 45 to 86 years. The size of pressure ulcers in ischial tuberosity ranged from 1.5 cm×1.0 cm to 8.0 cm×5.0 cm, and the size of pressure ulcers in greater trochanter ranged from 4.0 cm×3.0 cm to 20.0 cm×10.0 cm before debridement. After treatment of underlying diseases, debridement and vacuum sealing drainage for 5 to 14 days were performed. All the wounds were repaired by island posterior femoral composite tissue flaps, with area of 4.5 cm×3.0 cm-24.0 cm×12.0 cm, pedicle width of 3-5 cm, pedicle length of 5-8 cm, and rotation radius of 30-40 cm. Most of the donor site wounds were sutured directly, and only 4 donor site wounds were repaired by intermediate thickness skin graft from the contralateral thigh. The survival of composite tissue flaps, wound healing of the donor and recipient sites and the complications were observed. The recurrence of pressure ulcers, and the appearance and texture of flaps were observed during follow-up. Results: A total of 32 wounds in 23 patients were repaired by island posterior femoral composite tissue flaps (including 3 fascio subcutaneous flaps, 24 fascial flaps+fascio subcutaneous flaps, 2 fascial flaps+fascial dermal flaps, 2 fascial flaps+fascio subcutaneous flaps+femoral biceps flaps, and one fascial flap+fascio subcutaneous flap+gracilis muscle flap). Among them, 31 composite tissue flaps survived well, and a small portion of necrosis occurred in one fascial flap+fascio subcutaneous flap post surgery. The survival rate of composite tissue flap post surgery was 96.9% (31/32). Twenty-nine wounds in the recipient sites were healed, and 2 wounds were torn at the flap pedicle due to improper postural changes, and healed one week after bedside debridement. One wound was partially necrotic due to the flap bruising, and healed 10 days after re-debridement. Thirty-one wounds in the donor sites (including 4 skin graft areas) were healed, and one wound in the donor site was torn due to improper handling at discharge, and healed 15 days after re-debridement and suture. The complication rate was 12.5% (4/32), mainly the incision dehiscence of the flap pedicle and the donor sites (3 wounds), followed by venous congestion at the distal end of flap (one wound). During the follow-up of 3 to 24 months, the pressure ulcers did not recur and the flaps had good appearance and soft texture. Conclusions: The island posterior femoral composite tissue flaps has good blood circulation, large rotation radius, and sufficient tissue volume. It has a high survival rate, good wound healing, low skin grafting rate in the donor site, few postoperative complications, and good long-term effect in the repair of sinus cavity pressure ulcers in the areas of ischial tuberosity and greater trochanter.

Psychoimmunological effects of dioscorea in ovariectomized rats: role of anxiety level.

BACKGROUND: Anxiety levels in rats are correlated with interleukin-2 (IL-2) levels in the brain. The aim of the present study was to investigate the effects of dioscorea (wild yam), a Chinese medicine, on emotional behavior and IL-2 levels in the brain of ovariectomized (OVX) rats. METHODS: One month after ovariectomy, female Wistar rats were screened in the elevated plus-maze (EPM) test to measure anxiety levels and divided into low anxiety (LA) and high anxiety (HA) groups, which were then given dioscorea (250, 750, or 1500 mg/kg/day) by oral gavage for 27 days and were tested in the EPM on day 23 of administration and in the forced swim test (FST) on days 24 and 25, then 3 days later, the brain was removed and IL-2 levels measured. RESULTS: Compared to sham-operated rats, anxiety behavior in the EPM was increased in half of the OVX rats. After chronic dioscorea treatment, a decrease in anxiety and IL-2 levels was observed in the HA OVX rats. Despair behavior in the FST was inhibited by the highest dosage of dioscorea. CONCLUSION: These results show that OVX-induced anxiety and changes in neuroimmunological function in the cortex are reversed by dioscorea treatment. Furthermore, individual differences need to be taken into account when psychoneuroimmunological issues are measured and the EPM is a useful tool for determining anxiety levels when examining anxiety-related issues.

Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma / 中华医学杂志(英文版)

Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis, allergic asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps. It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion. Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma, which may partly explain the increasing prevalence of asthma in China and around the globe. The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community. The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter- and sub-epithelial areas and the development of epithelial tissue inflammation. Accordingly, preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma. This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma, the structure and molecular composition of the airway epithelial barrier, and the assessment of epithelial barrier integrity. The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed. In addition, the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants, and current treatments to restore the airway epithelial barrier are reviewed.

Optimal Dietary and Plasma Magnesium Statuses Depend on Dietary Quality for a Reduction in the Risk of All-Cause Mortality in Older Adults.

The association between dietary or plasma magnesium (Mg) with diabetes incidence and with mortality in free-living elderly was investigated. A total of 1400 participants from the Taiwanese Nutrition Survey, aged ≥ 65 years, and diabetes-free from the 1999-2000 were assessed. The dietary intake and plasma Mg concentration were obtained through 24h dietary recall and health examination at baseline. Participants were classified by quartiles (Q) of dietary Mg or by the plasma Mg normal range (0.75-0.95 mmol/L). Dietary diversity score (DDS, range 1-6) represented the dietary quality. During 8 and 10 years, 231 incident diabetes cases and 475 deaths were identified. Cox's proportional-hazards regression was used to evaluate the association between Mg and health outcomes. The hazard ratios (95% confidence interval) for death in Q2 and Q3 of Mg intakes with DDS > 4 were 0.57 (0.44-0.74) and 0.59 (0.39-0.88), respectively, compared with the lowest intake and DDS ≤ 4 participants. Participants with normal and high plasma Mg in conjunction with high DDS had relative risks of 0.58 (0.37-0.89) and 0.46 (0.25-0.85) in mortality compared with low plasma Mg and lower DDS. Optimal dietary Mg intake and plasma Mg depend on dietary quality to reduce the mortality risk in older adults.

Naringenin ameliorates renal impairment by increasing 20-HETE in diabetic mice / 中国药理学通报

Aim: To investigate the ameliorative effects of naringenin on renal injury and its roles in 20-HETE in diabetic mice. Methods: A diabetic model was established by long-term high-energy feeding combined with streptozotocin. The structural and functional changes of kidney were evaluated by renal pathological examination and blood urea nitrogen(BUN), serum creatinine(SCr), urinary albumin levels. The expression of CYP4A protein was detected by Western blot. The level of 20-HETE was measured by ELISA kit. Results: After four weeks of high-energy feeding, streptozotocin (40 mg. kg-1. d-1, IP) was given for five days. Then after seven days, fasting blood glucose of mice exceeded 11.1 mmol L-1, which suggested the establishment of diabetic model. After four weeks of diabetic onset, the levels of BUN, SCr, urinary albumin increased significantly(P <0. 01); kidney index(renal weight/body weight) and glomerular volume were raised(P <0. 01); increased collagen fiber and thickened basement membrane were observed in diabetic mice. Meanwhile, the expression of CYP4A protein in the kidney and the content of 20-HETE in serum decreased in model group (P < 0. 01). With naringenin supplementation(25 or 75 mg · kg-1 · d-1) for four weeks, both the structure and function of kidney were improved in diabetic mice, with the up-regulation of CYP4A protein expression and the increase of 20- HETE level(P < 0. 05). Conclusion: Naringenin can ameliorate renal injury in diabetic mice, which may be related to activating CYP4A and increasing 20-HETE.

Role of 20-HETE in amelioration of renal impairment by bezafibrate in mice with diabetic nephropathy / 中国药理学通报

Aim To investigate the protective effect of bezafibrate on renal injury and the changcs of 20- HETE in mice with diabetic nephropathy. Methods A diabctic model was established by long-term high-energy feeding combined with streptozotocin. The structural and functional changes of kidney were evaluated by renal pathological examination and blood urea nitrogen (BUN), serum creatinine ( Scr) , urinary albumin levels. The expressions of PPAIls and CYP4A protein were detected by Western blot. The level of 20-HETE was measured by ELISA kit. Results After four weeks with high-energy feeding, streptozotocin (40 mg • kg-1 • d"1 i. p) administration had been performed for five days. Then after seven days,fasting blood glucose (FBG) of mice exceeded 11.1 nimol • L"1, which suggested the establishment of the diabetic model. After four weeks of diabetic onset, the levels of BUN,Scr,urinary albumin increased significantly (P er and thickened basement membrane were observed in diabetic mice. Meanwhile,the expressions of PPARs and CYP4A protein in the kidney and the content of 20-HETE in serum decreased in model group (P <0. 01). With bezafibrate supplementation (75 mg • kg"' • d"1) for four weeks, both the structure and function of kidney were improved in diabetic mice,with the up-regulation of PPARs and CYP4A protein expressions and the increase of 20-HETE level (P <0. 01 ). Conclusions Bezafibrate can ameliorate renal injury in diabetic mice, which may be related to activating CYP4A-20-HETE.

Effect of Pien Tze Huang on bile excretion and its analgesic effect in experimental animals / 临床肝胆病杂志

ObjectiveTo investigate the effect of Pien Tze Huang on bile excretion and its analgesic effect in experimental animals. MethodsA total of 30 guinea pigs were randomly divided into Pien Tze Huang group, ursodeoxycholic acid group, and control group. According to body mass, the three groups were treated with Pien Tze Huang (140 mg/kg), ursodeoxycholic acid (22.5 mg/kg), and normal saline, respectively, by gavage for 4 consecutive days. Then bile drainage was performed to measure the volume of bile secretion and the change in bile composition. Related liver function parameters were also measured. A total of 30 mice were randomly divided into Pien Tze Huang group (360 mg/kg), ursodeoxycholic acid group (120 mg/kg), and control group. At one hour after the last administration, the mice were given intraperitoneal injection of 0.6% glacial acetic acid (0.15 ml/10 g), and the writhing test was performed to observe the analgesic effect of Pien Tze Huang. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group, the Pien Tze Huang group and the ursodeoxycholic acid group had a significant increase in the volume of bile secretion (P=0.039 and 0.009). There were no significant differences between the three groups in cholesterol, bilirubin, total bile acid, and phospholipid in bile (all P＞0.05) and liver function parameters (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, direct bilirubin, indirect bilirubin, and total bile acid) (all P＞0.05). Compared with the control group, the Pien Tze Huang group had a significant reduction in the number of writhing times (P＜0.001), suggesting that Pien Tze Huang had a marked analgesic effect. ConclusionAnimal experiments show that Pien Tze Huang has marked choleretic and analgesic effects, which provides theoretical and data support for the clinical application of Pien Tze Huang.

Effect of Pien Tze Huang on bile excretion and its analgesic effect in experimental animals / 临床肝胆病杂志

ObjectiveTo investigate the effect of Pien Tze Huang on bile excretion and its analgesic effect in experimental animals. MethodsA total of 30 guinea pigs were randomly divided into Pien Tze Huang group, ursodeoxycholic acid group, and control group. According to body mass, the three groups were treated with Pien Tze Huang (140 mg/kg), ursodeoxycholic acid (22.5 mg/kg), and normal saline, respectively, by gavage for 4 consecutive days. Then bile drainage was performed to measure the volume of bile secretion and the change in bile composition. Related liver function parameters were also measured. A total of 30 mice were randomly divided into Pien Tze Huang group (360 mg/kg), ursodeoxycholic acid group (120 mg/kg), and control group. At one hour after the last administration, the mice were given intraperitoneal injection of 0.6% glacial acetic acid (0.15 ml/10 g), and the writhing test was performed to observe the analgesic effect of Pien Tze Huang. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group, the Pien Tze Huang group and the ursodeoxycholic acid group had a significant increase in the volume of bile secretion (P=0.039 and 0.009). There were no significant differences between the three groups in cholesterol, bilirubin, total bile acid, and phospholipid in bile (all P＞0.05) and liver function parameters (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, direct bilirubin, indirect bilirubin, and total bile acid) (all P＞0.05). Compared with the control group, the Pien Tze Huang group had a significant reduction in the number of writhing times (P＜0.001), suggesting that Pien Tze Huang had a marked analgesic effect. ConclusionAnimal experiments show that Pien Tze Huang has marked choleretic and analgesic effects, which provides theoretical and data support for the clinical application of Pien Tze Huang.

Reverse phase high-performance liquid chromatography (RP-HPLC) system for analysis of vitamin D3 soft capsules with soybean oil matrix / 复旦学报（医学版）

Objective To develop a method for the determination and impurity analysis of vitamin D3 soft capsules with soybean oil matrix in reverse phase high performance liquid chromatography (RP-HPLC) system.Methods RP-HPLC system had Agilent Zorbax Eclipse XDB-C18 column (4.6 mm × 250 mm,5 ttm) with detection wavelength of 265 nm,column temperature of 25 ℃ and flow rate of 1 mL/min.Retention behaviors of vitamin D3 and its 3 isomers were studied by altering the mobile phase.Firstly,acetonitrile was mixed with different proportions of methanol,water and ethanol as the mobile phase to investigate the effects of these 4 mobile phase components on the retention behavior of vitamin D3 and its 3 main related substances (isomers) on a C18 column.Then,a suitable mobile phase was selected for content determination and impurity analysis according to the retention behavior study.Results The recovery was only 80.55％-84.37％ with 100％ acetonitrile as the mobile phase.The addition of ethanol in acetonitrile was found to make remarkably significant improvement.Recovery rate was achieved between 98.07 ％ and 103.23 ％ with V (acetonitrile) ∶V (ethanol) =90∶10 as the mobile phase,while improving pealk shape.The method showed good linearity [(0.52-5.2) x 10-4 t mol/L,R2＞0.999] and fine density (RSD＜2.32％) which can be used for determination.For impurities profile,it could be achieved using V (acetonitrile):V (water) =95:5 as the mobile phase which can obviate interference from soybean oil matrix.Conclusions The method established in this experiment can easily and accurately determine the content and impurity analysis of vitamin D3 soft capsules with soybean oil matrix in a RP-HPLC system.