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 new aspects of the systemic and cellular lipid metabolism in FD, a possible involvement of platelets in FD, and potential novel markers for FD screening and monitoring.

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.

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.

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.

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 .

Regulation of mRNA transcripts, protein isoforms, glycosylation and spatial localization of ACE2 and other SARS-CoV-2-associated molecules in human airway epithelium upon viral infection and type 2 inflammation

SARS-CoV-2 infection continues to pose a significant life threat, especially in patients with comorbidities. It remains unknown, if asthma or allergen- and virus-induced airway inflammation are risk factors or can constitute some forms of protection against COVID-19. ACE2 and other SARS-CoV-2-related host proteins are limiting factors of an infection, expression of which is regulated in a more complex way than previously anticipated. Hence, we studied the expression of ACE2 mRNA and protein isoforms, together with its glycosylation and spatial localization in house dust mite (HDM)-, interleukin-13 (IL-13)- and human rhinovirus (RV)-induced inflammation in the primary human bronchial airway epithelium of healthy subjects and patients with asthma. IL-13 decreased the expression of long ACE2 mRNA and glycosylation of full-length ACE2 protein via alteration of the N-linked glycosylation process, limiting its availability on the apical side of ciliated cells. RV infection increased short ACE2 mRNA, but it did not influence its protein expression. HDM exposure did not affect ACE2 mRNA or protein. IL-13 and RV significantly regulated mRNA, but not protein expression of TMPRSS2 and NRP1. Regulation of ACE2 and other host proteins was similar in healthy and asthmatic epithelium, underlining the lack of intrinsic differences, but rather the dependence on the inflammatory milieu in the airways.

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.

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.

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.

Physical development monitoring of primary school students in the Oroqen Inhabited Area from 2013 to 2018 / 中国学校卫生

Objective@#To understand physical development of children aged 7 to 12 in the oroqen autonomous banner experimental primary school in the oroqen settlement area from 2013 to 2018, and to provide scientific basis for their physical fitness and health.@*Methods@#According to the standards of "National Student Physical Health Standards (2014 Revised Edition)" and the standards of "Overweight and Obesity Screening for School age Children and Adolescents" issued by the National Health and Family Planning Commission in 2018, the Oroqen Autonomous Banner Experimental Primary School was 7-12 years old. The average value and growth rate of children s height, weight and BMI in the past 6 years.@*Results@#From 2013 to 2018, the height and weight of boys and girls aged 7 to 12 showed an increasing trend, with height growth values of boys were 1.8,1.7,1.9,2.6,5.7,5.9 cm,girls were 2.8,4.5,1.9,1.8,3.6,2.9 cm.And the weight groups values of boys were 2.2,2.5,5.1,6.3,6.4,7.2 kg,girls were 2.4,3.6,3.1,1.3,4.6,3.0 kg. The growth rate of girls aged 7 to 8 was higher than that of boys, and the growth rate of boys aged 9 to 12 was higher than that of girls. With the increase of age, the average BMI of boys and girls aged 7 to 12 showed an upward trend, and the BMI of boys of the same age was always higher than that of girls. Among them, the average BMI of boys aged 7 to 12 in 2018 exceeded the critical value of overweight BMI.@*Conclusion@#The physical shape of children aged 7-12 years increases with age, but the development tends to be overweight and obese, which is related to the natural environment of life, lifestyle, and reduction in physical activity.

Distribution of ACE2, CD147, cyclophilins, CD26 and other SARS-CoV-2 associated molecules in human tissues and immune cells in health and disease

BackgroundMorbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. MethodsWe performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. ResultsACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2- and CD147-related genes in the lesional skin of patients with atopic dermatitis. ConclusionsOur data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID-19 morbidity and severity patterns.

Comparison of physical health of De’ang and Han pupils in Dehong Prefecture / 中国学校卫生

Objective@#To understand the differences in physical indices, physical functions, and physical fitness among primary school students of De’ang and Han nationalities in the De’ang community, and to provide a reference for the healthy development of the physique of children and adolescents.@*Methods@#The cluster sampling method was used to select the test data of height, weight, vital capacity, 50 meter running, seated forward flexion, and 1 minute skipping rope of 2 493 De’ang and Han pupils in five complete primary schools in Mangshi, Dehong Prefecture. Differences in each indices were compared between groups.@*Results@#For physical indicators: height in boys in 8,9 and 11 year old group, girls in 7 and 8 year old group, were significantly higher in Han nationality,weight among Han boys of 9 years old was higher than Deang nationality; For physical function indicators: vital capacity of girls 11 years old group and 12 years old group, boys 9 years old group, 10 years old group, 12 years old group, children of Han nationality were higher than Deang peers. For physical fitness indicators: in 50 m running, Han boys of 8,9,10 and 12 year old,as well as Han girls of 8 year old were higher than age matched peers of De’ang nationality;For seated forward flexion, Han boys of 11 years old and girls of 9 years old, were lower than Deang; in 1 min skipping, Han boys of 9,10,11 and 12 year old,as well as Han girls of 9 and 10 year old, were lower than the De’ang nationality.@*Conclusion@#Unbalanced development of physical fitness is observed among primary school students of De’hong and Han nationality, with significant differences in physical, functional and fitness indices.

Efficacy of transversus abdominis plane block combined with butopenol PCIA for analgesia after cesarean section under general anesthesia / 中华麻醉学杂志

Objective To evaluate the efficacy of transversus abdominis plane (TAP) block combined with butopenol patient-controlled intravenous analgesia (PCIA) for analgesia after cesarean section under general anesthesia.Methods Ninety American Society of Anesthesiologists physical status Ⅰ or Ⅱ parturients,aged 18-42 yr,weighing 52-88 kg,at 38-42 weeks of gestation,scheduled for elective cesarean section under general anesthesia,were divided into 3 groups (n=30 each) using a random number table method:TAP block group (group TAP),butopenol PCIA group (group B) and TAP block plus butopenol PCIA group (group TB).In group TAP,bilateral TAP blocks were performed under ultrasound guidance at the end of surgery,and 0.375％ ropivacaine 20 ml was injected into each side.In group B,butopenol 1 mg was intravenously injected at 30 min before the end of operation,PCIA was performed at the end of surgery,PCIA solution contained butopenol 8 mg and ondansetron 8 mg (diluted to 100 ml in sodium chloride injection),and the PCIA pump was set up to deliver a 0.5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.Butopenol 1 mg was intravenously injected at 30 min before the end of operation,and TAP block in combination with butopenol PCIA was performed at the end of operation in group TB.When the postoperative visual analog scale score was greater than or equal to 4 points,morphine 10 mg was intramuscularly injected as rescue analgesic.The requirement for morphine was recorded within 48 h after operation.The occurrence of agitation during emergence from anesthesia and adverse reactions within 48 h after operation were also recorded.Results No adverse reactions such as hematoma at the puncture site or local anesthetic intoxication were observed in TAP group and TB group.Compared with group TAP,the incidence of postoperative shivering and requirement for morphine were significantly decreased in group TB (P＜0.05).The incidence of postoperative nausea and v omiting and requirement for morphine were significantly lower in group TB than in group B (P＜0.05).Conclusion The combination of TAP block and butopenol PCIA exerts better efficacy for analgesia after cesarean section under general anesthesia than either alone.

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.

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.

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.

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.

Expression of calreticulin and its relationship with autoantibodies and inflammatory cytokines in early rheumatoid arthritis / 天津医药

Objective To investigate the expression of calreticulin and its correlation with autoantibodies and inflammatory cytokines in patients with early rheumatoid arthritis (RA). Methods Serum samples were obtained from 106 patients with early active RA, 95 patients with stable RA, 85 osteoarthritis (OA) and 80 healthy controls (HC). Serum levels of calreticulin, anti- cyclic peptide antibody (CCP), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were measured by enzyme-linked immnuosorbent assay (ELISA). The serum level of rheumatoid factor (RF) was detected by immunoturbidimetry. The correlations between serum calreticulin and inflammatory cytokines were evaluated using Spearman's rank correlation test. Results Serum levels of calreticulin were significantly higher in patients with early active RA [(5.84±2.62)μg/L] than those in patients with stable RA [(4.26±1.42)μg/L], patients with OA [(3.92±1.10)μg/L] and HC [(3.86 ± 0.91)μg/L] (P<0.001). There were no statistical differences in serum levels of calreticulin between stable RA, OA and HC groups (P>0.05). Serum levels of calreticulin were significantly higher in RF-positive RA patients than those of RF-negative RA patients [(6.12±2.87)μg/L vs. (4.92±1.22)μg/L, P=0.045]. Serum calreticulin levels were also significantly higher in anti-CCP-positive RA patients than those of anti-CCP-negative RA patients [(6.39±2.93)μg/L vs. (4.69±1.17)μg/L, P=0.002]. The serum level of calreticulin was positively correlated with IL-1β (rs=0.386, P=0.009), IL-6 (rs=0.405, P=0.006) and TNF-α(rs=0.428, P=0.003) in early active RA patients. Conclusion The elevated serum level of calreticulin is related to autoantibodies and inflammatory cytokines in early RA patients, suggesting that calreticulin can be used as a potential biomarker for early diagnosis and prognosis of RA.

Population-based study on the relationship between folic acid supplementation and the occurrence risk of congenital heart defects / 复旦学报（医学版）

Congenital heart disease (CHD) is the most common congenital malformations.It occurs under the combined effect of genetic and environmental factors.In recent years,the correlation of key nutritional factors,the modifiable environmental factors,with the occurrence risk of CHD has attracted increasing attention.One of the most representative key nutritional factors is folic acid,and many studies suggest that maternal folic acid supplementation during periconceptional period could reduce the risk of CHD occurrence.However,many challenges remain in order to clarify the relationship between folic acid and CHD,which is worthy of further study.