Retinal microvascular changes in patients with pancreatitis and their clinical significance.

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

Effects of High-Hydrostatic-Pressure Treatment on Polyphenols and Volatile Aromatic Compounds in Marselan Wine.

This study investigated the effects of high-hydrostatic-pressure (HHP) treatment of varying intensity (100-600 MPa) and duration (10-30 min) on polyphenols and volatile aromatic compounds in Marselan red wine. The types and concentrations of polyphenols and volatile aromatic compounds were compared before and after HHP treatment; the results indicated that HHP treatment at 300 MPa for 20 min significantly increased the total polyphenol content to 369.70 mg/L, a rise of 35.82%. The contents of key polyphenols, such as resveratrol and protocatechuic acid, were significantly enhanced. Furthermore, while the total content of volatile aromatic compounds did not change significantly under this condition compared to the untreated samples, the concentration of ester compounds significantly increased to 1.81 times that of the untreated group, thereby enriching the floral and fruity aromas of the wine and effectively improving its aromatic profile and sensory quality. Principal component analysis (PCA) further validated the positive impact of HHP treatment on the flavor characteristics of Marselan red wine. These findings provide technical support for the use of HHP in improving wine quality.

Geographical characterization of wines from seven regions of China by chemical composition combined with chemometrics: Quality characteristics of Chinese 'Marselan' wines.

This study investigated the basic and functional compositions, volatile compounds, intelligent sensory characteristics and antioxidant capacity of the commercial 'Marselan' wines from seven Chinese regions. The Nei Mongol wines featured high total reducing sugar, fructose, ammonia nitrogen, 17 monomeric phenolic acids contents and elevated antioxidant capacity. Malic acid was the only organic acid that significantly different in all seven regions. Malvidin-3-O-glucoside and trans-peonidin-3-O-(6-O-p-coumaryl)-glucoside showed the highest and lowest contents. A total of 102 volatiles was detected and Hebei wines had the most (91). Hexanoic acid and ß-damascenone were considered to have high potential sensory effects (OAV ≥ 1) as compounds detected in all regions. Floral, sweet, and fruity were the most important aroma series. E-eye analysis revealed the colors of the samples tended to yellowish with aging. PCA and OPLS-DA based on the basic wine composition, monomeric organic acids and anthocyanins allowed achieving a discrimination of the seven regions, respectively.

Different emotional states engage distinct descending pathways from the prefrontal cortex.

Emotion regulation, essential for adaptive behavior, depends on the brain's capacity to process a range of emotions. Current research has largely focused on individual emotional circuits without fully exploring how their interaction influences physiological responses or understanding the neural mechanisms that differentiate emotional valence. Using in vivo calcium imaging, electrophysiology, and optogenetics, we examined neural circuit dynamics in the medial prefrontal cortex (mPFC), targeting two key areas: the basal lateral amygdala (BLA) and nucleus accumbens (NAc). Our results demonstrate distinct activation patterns in the mPFC→BLA and mPFC→NAc pathways in response to social stimuli, indicating a mechanism for discriminating emotions: increased mPFC→BLA activity signals anxiety, while heightened mPFC→NAc responses are linked to exploration. Additionally, chronic emotional states amplify activity in these pathways-positivity enhances mPFC→NAc, while negativity boosts mPFC→BLA. This study sheds light on the nuanced neural circuitry involved in emotion regulation, revealing the pivotal roles of mPFC projections in emotional processing. Identifying these specific circuits engaged by varied emotional states advances our understanding of emotional regulation's biological underpinnings and highlights potential targets for addressing emotional dysregulation in psychiatric conditions. Significance statement: While existing circuitry studies have underscored the significance of emotional circuits, the majority of research has concentrated on individual circuits. The assessment of whether and how the balance among multiple circuits influences overall physiological outcomes is often overlooked. This study delves into the neural underpinnings of emotion regulation, focusing on how positive and negative valences are discriminated and managed. By examining the specific pathways from the medial prefrontal cortex (mPFC) to key emotional centers-the basal lateral amygdala (BLA) for negative valence and the nucleus accumbens (NAc) for positive one-we uncovered a novel dual-balanced neural circuit mechanism that enables this essential aspect of human cognition.

Dietary supplements: clinical cholesterol-lowering efficacy and potential mechanisms of action.

This review aims to analyse the efficacy of dietary supplements in reducing plasma cholesterol levels. Focusing on evidence from meta-analyses of randomised controlled clinical trials, with an emphasis on potential mechanisms of action as supported by human, animal, and cell studies. Certain dietary supplements including phytosterols, berberine, viscous soluble dietary fibres, garlic supplements, soy protein, specific probiotic strains, and certain polyphenol extracts could significantly reduce plasma total and low-density lipoprotein (LDL) cholesterol levels by 3-25% in hypercholesterolemic patients depending on the type of supplement. They tended to be more effective in reducing plasma LDL cholesterol level in hypercholesterolemic individuals than in normocholesterolemic individuals. These supplements worked by various mechanisms, such as enhancing the excretion of bile acids, inhibiting the absorption of cholesterol in the intestines, increasing the expression of hepatic LDL receptors, suppressing the activity of enzymes involved in cholesterol synthesis, and activating the adenosine monophosphate-activated protein kinase signalling pathway.

Meta-analysis and machine learning reveal the antiobesity effects of melatonin on obese rodents.

Melatonin appears to be a promising supplement for obesity treatment. The antiobesity effects of melatonin on obese rodents are influenced by various factors, including the species, sex, the dosage of melatonin, treatment duration, administration via, daily treatment time, and initial body weight (IBW). Therefore, we conducted a meta-analysis and machine learning study to evaluate the antiobesity effect of melatonin on obese mice or rats from 31 publications. The results showed that melatonin significantly reduced body weight, serum glucose (GLU), triglycerides (TGs), low-density lipoprotein (LDL), and cholesterol (TC) levels in obese mice or rats but increased high-density lipoprotein (HDL) levels. Melatonin showed a slight positive effect on clock-related genes, although the number of studies was limited. Meta-regression analysis and machine learning indicated that the dosage of melatonin was the primary factor influencing body weight, with higher melatonin dosages leading to a stronger weight reduction effect. Together, male obese C57BL/6 mice and Sprague-Dawley rats with an IBW of 100-200 g showed better body weight reduction when supplemented with a dose of 10-30 mg/kg melatonin administered at night via injection for 5-8 weeks.

Ocular microvascular alteration in patients with myocardial infarction-a new OCTA study.

Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p < 0.05 each). In the deep layers, the deep MIR and deep TMI), as well as densities in the SL, IL, L, C1, C2 and C6 regions were significantly lower in MI patients (p < 0.05 each). In contrast, the conjunctival microvascular density was significantly higher in MI patients than in healthy controls (p < 0.001). The microvascular densities measured in the deep and superficial retinal layers and in the conjunctiva differ in MI patients and healthy controls. OCTA is effective in detecting changes in the ocular microcirculation.

Acid-Sensing Ion Channel 1a Contributes to the Prefrontal Cortex Ischemia-Enhanced Neuronal Activities in the Amygdala.

Following a stroke, the emergence of amygdala-related disorders poses a significant challenge, with severe implications for post-stroke mental health, including conditions such as anxiety and depression. These disorders not only hinder post-stroke recovery but also elevate mortality rates. Despite their profound impact, the precise origins of aberrant amygdala function after a stroke remain elusive. As a target of reduced brain pH in ischemia, acid-sensing ion channels (ASICs) have been implicated in synaptic transmission after ischemia, hinting at their potential role in reshaping neural circuits following a stroke. This study delves into the intriguing relationship between post-stroke alterations and ASICs, specifically focusing on postsynaptic ASIC1a enhancement in the amygdala following prefrontal cortex (PFC) ischemia induced by endothelin-1 (ET-1) injection. Our findings intriguingly illustrate that mPFC ischemia not only accentuates the PFC to the amygdala circuit but also implicates ASIC1a in fostering augmented synaptic plasticity after ischemia. In contrast, the absence of ASIC1a impairs the heightened induction of long-term potentiation (LTP) in the amygdala induced by ischemia. This pivotal research introduces a novel concept with the potential to inaugurate an entirely new avenue of inquiry, thereby significantly enhancing our comprehension of the intricate mechanisms underlying post-stroke neural circuit reconfiguration. Importantly, these revelations hold the promise of paving the way for groundbreaking therapeutic interventions.

Using abandoned unripe grape resources to solve the low-acid problem in the northwest wine region of China.

Low acid is the main defect in the northwest wine region of China in recent years. The fermentation of unripe grape (UG) and wine grapes with low acid contents was carried out. Compared with control group (CK), the addition of UG addressed the core flaw that low acid grape bring to wine firstly, it significantly increased titratable acid, tartaric acid and malic acid while significantly decreasing alcohol and volatile acids in wine. Secondly, UG significantly improved wine color, the color parameters a*, b*, C* and L* were significantly increased to different degrees. At the same time, the addition of UG significantly improves other qualities of wine, including the phenolic substances and antioxidant capacity of wine. In addition, adding UGJ2% significantly improved the sensory quality, and pleasant volatile substances such as phenethyl alcohol, ethyl hexanoate, ethyl butyrate and isoamyl acetate were significantly increased, giving the wine more prominent floral and fruity aromas.

Characteristics of Syndrome Differentiation and Immune Imbalance in Children with Atopic Dermatitis / 世界科学技术-中医药现代化

Objective To investigate the syndrome differentiation characteristics of children with atopic dermatitis(AD)and the immune imbalance status in children with different syndrome types of AD.Methods A total of 159 AD children and 100 normal control children were enrolled.The peripheral blood eosinophil(Eo)count was measured by impedance method,total serum immunoglobulin E(IgE)by immunoturbidimetric assay,and interferon-gamma(IFN-γ),interleukin-4(IL-4),interleukin-5(IL-5)and interleukin-17(IL-17)were measured by multiple microspheres flow immunofluorescence assay.Results Among 159 AD children,syndrome of heart-fire and spleen-deficiency was most commom,accounting for 38.4%,followed by syndrome of blood-deficiency and wind-dryness(22.0%),syndrome of heat accumulation in heart and spleen(20.1%)and syndrome of spleen-deficiency and dampness-accumulation(19.5%).Compared with normal control group,there was no significant difference in serum IFN-γ level among different syndrome types of AD.The levels of peripheral blood Eo,serum total IgE,IL-4 and IL-17 in AD with heart-fire and spleen-deficiency syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo,IL-4,IL-5 and IL-17 in AD with blood-deficiency and wind-dryness syndrome were significantly increased(P<0.05).The levels of IL-4,IL-5 and IL-17 in AD with heat accumulation in heart and spleen syndrome were significantly increased(P<0.05).The levels of peripheral blood Eo and serum IL-4 in AD with spleen-deficiency and dampness-accumulation syndrome were significantly increased(P<0.05).Conclusion Heart-fire and spleen-deficiency syndrome is the most common type in children with AD,however,the main type under 3 years old is heat accumulation in heart and spleen syndrome.Th2/Th17 immune imbalance are the main pathogenesis in heart-fire and spleen-deficiency syndrome,blood-deficiency and wind-dryness syndrome and heat accumulation in heart and spleen syndrome,and Th2 immune imbalance is the main pathogenesis of spleen-deficiency and dampness-accumulation syndrome.

Analysis of clinical features of 78 infants with scabies / 中华皮肤科杂志

Objective:To analyze clinical features of 78 infants with scabies and their causes of misdiagnosis.Methods:A retrospective analysis was performed on infants aged < 6 months with confirmed scabies at Department of Dermatology in Zhengzhou Children′s Hospital, Jingjiang People′s Hospital, Tangdu Hospital of the Fourth Military Medical University, Second Affiliated Hospital of Soochow University and Henan Provincial People′s Hospital from January 1, 2016 to December 31, 2018. Then, epidemiological features, skin lesion characteristics, treatment and causes of misdiagnosis of infantile scabies were analyzed.Results:A total of 78 infants with scabies were collected. Their age of onset and duration from onset to diagnosis [ M ( P25, P75) ] were 8.5 (7, 12) and 4 (3.5, 5) weeks respectively. At the time of diagnosis, 45 (57.7%) patients showed lower body weight than the first quartile [ P25] of body weight of age- and gender-matched healthy peers, 40 (47.4%) had fussiness and irritation, and 68 (87.2%) had sleep disorders like night crying and increased frequency of night waking. Infantile scabies more frequently occurred in autumn (30 cases [38.5%]) and winter (22 cases [28.2%]) , and least frequently occurred in summer (8 cases [10.3%]) . In the case of 58 patients, there was at least 1 member with scabies at the same time, who had resided with the patients in their families for a long time; in the case of 12 patients, scabies was transmitted through previous contact with temporary residents with scabies in their families. Scabies lesions most commonly occurred on the chest and abdominal regions (80.8%) , followed by the limbs (76.9%) ; skin lesions were polymorphic, and lesions at different stages could coexist; the rashes mainly manifested as edematous red or non-edematous brown papules, blisters, papulovesicles and nodules, and some burrows could be characterized by an oval, linear, serpiginous, comma- or J-shaped appearance. All the patients had visited the clinic for 1 - 4 times with an average of 2.38 visits. Forty-eight (61.5%) patients initially visited non-dermatology departments, and 30 (38.5%) initially visited dermatological outpatient clinics. Incorrect diagnoses included infantile eczema, papular urticaria, impetigo, miliaria, prurigo, urticaria pigmentosa, infantile acropustulosis, herpes simplex and varicella. All the patients received topical sulfur 5% ointment. Nine (11.5%) patients experienced a sudden exacerbation of skin lesions after the topical treatment, and 20 (25.6%) needed 2 - 3 sessions of treatment. No recurrence was observed in all the patients at 2, 4 and 8 weeks after the end of treatment. Conclusions:Infantile scabies lesions are polymorphic, widely distributed, and easily misdiagnosed. To prevent misdiagnosis and improve the early diagnosis rate, a detailed clinical interrogation with clinical-epidemiological examination should be performed.

Association of metabolic syndrome with chronic kidney disease in premenopausal and postmenopausal women / 南方医科大学学报

OBJECTIVE@#To explore the relationship between metabolic syndrome (MS) and the risk for chronic kidney disease (CKD) in premenopausal and postmenopausal women.@*METHODS@#We conducted a cross-sectional study among 1346 community-based women from June to October 2012 and collected the data of personal history, lifestyle, physical measures and laboratory indicators. The diagnosis of CKD was established for an eGFR of less than 60 mL/min per 1.73 m or albuminuria. The diagnosis of metabolic syndrome was based on the International Diabetes Federation Guide. According to an epidemiological survey in Guangdong province, women older than 48.9 years were classified as having a postmenopausal status. The prevalence of MS and CKD was determined in both the premenopausal and postmenopausal women, and the association between MS and CKD was analyzed using logistic regression models.@*RESULTS@#MS was significantly correlated with CKD in premenopausal women in both unadjusted analyses (OR=3.10, 95% : 1.32-7.28, =0.009) and in analysis after adjustment for potential confounders (OR=4.09, 95% : 1.63- 10.32, =0.003). When adjusted for diabetes, hypertension, and hyperuricemia, no correlation was found between MS and CKD in premenopausal women (OR=1.56, 95% : 0.31-7.63, = 0.592); in the unadjusted analyses, MS was significantly correlated with CKD in postmenopausal women ( < 0.001). After further adjustment for age, education status, current smoking, physical inactivity, and current drinking, MS was still significantly correlated with CKD (OR=2.60, 95% : 1.69-3.99, < 0.001). When adjusted for diabetes, hypertension, and hyperuricemia, the correlation between MS and CKD was still significant (OR=1.61, 95% : 1.09-2.37, =0.018). In the unadjusted model, a high blood pressure (OR=2.77, 95%CI: 1.57-4.89, < 0.001), an elevated serum triglyceride level (OR=1.84, 95%: 1.16-2.90, =0.009) and a high fast glucose level (OR=2.07, 95%: 1.30-3.28, =0.002) were all significantly correlated with CKD in postmenopausal women. After adjusting for age, current smoking, current alcohol use, education status and physical inactivity, a high blood pressure (OR=2.28, 95%: 1.22-4.26, =0.01), a high serum triglyceride level (OR=1.71, 95%: 1.03-2.86, =0.039) and a high fast glucose (OR=2.25, 95%: 1.36-3.73, =0.002) were still significantly correlated with CKD in postmenopausal women. Blood pressure, serum triglyceride level, fast glucose, serum HDL cholesterol level and central obesity were not correlated with CKD in either the unadjusted model or adjusted model in premenopausal women ( > 0.05).@*CONCLUSIONS@#MS is correlated with CKD in both premenopausal and postmenopausal women, and the association is dependent on diabetes, hypertension, and hyperuricemia in premenopausal women but not in postmenopausal women.

S100 calcium binding protein A16 promotes fat synthesis through endoplasmic reticulum stress in HepG2 cells / 生理学报

The aim of this study was to investigate the role of S100 calcium binding protein A16 (S100A16) in lipid metabolism in hepatocytes and its possible biological mechanism. HepG2 cells (human hepatoma cell line) were cultured with fatty acid to establish fatty acid culture model. The control model was cultured without fatty acid. Each model was divided into three groups and transfected with S100a16 over-expression, shRNA and vector plasmids, respectively. The concentration of triglyceride (TG) in the cells was measured by kit, and the lipid droplets was observed by oil red O staining. Immunoprecipitation and mass spectrometry were used to find the interesting proteins interacting with S100A16, and the interaction was verified by immunoprecipitation. The further mechanism was studied by Western blot and qRT-PCR. The results showed that the intracellular lipid droplet and TG concentrations in the fatty acid culture model were significantly higher than those in the control model. The accumulation of intracellular fat in the S100a16 over-expression group was significantly higher than that in the vector plasmid transfection group. There was an interaction between heat shock protein A5 (HSPA5) and S100A16. Over-expression of S100A16 up-regulated protein expression levels of HSPA5, inositol-requiring enzyme 1α (IRE1α) and pIREα1, which belong to endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway. Meanwhile, over-expression of S100A16 up-regulated the mRNA expression levels of adipose synthesis-related gene Srebp1c, Acc and Fas. In the S100a16 shRNA plasmid transfection group, the above-mentioned protein and mRNA levels were lower than those of vector plasmid transfection group. These results suggest that S100A16 may promote lipid synthesis in HepG2 cells through endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway.

Expression of serum neutrophil gelatinase-associated lipocalin in children with psoriasis and its pathogenic mechanisms / 中华皮肤科杂志

Objective To explore the relationships of neutrophil gelatinase-associated lipocalin (NGAL) with severity of skin lesions in children with psoriasis and peripheral neutrophil count,and to evaluate in vitro effect of NGAL on expression of tumor necrosis factor-α (TNF-α) and interleukin-22 (IL-22) by a human immortalized keratinocyte cell line HaCaT.Methods From January 1st 2017 to December 31st 2018,98 children who newly developed psoriasis were enrolled from Department of Dermatology of 6 hospitals in China,including 51 males and 47 females.Their age was 7.00 ± 2.99 years (range:3-14 years),and their course of disease was 7.4 ± 5.85 days (range:3-28 days).The serum level of NGAL was detected in all the patients before and two weeks after treatment,and the relationships of NGAL with psoriasis area and severity index (PASI) scores and peripheral neutrophil count were evaluated.Western blot analysis and reverse-transcription (RT)-PCR were performed to determine the protein and mRNA expression of TNF-α and IL-22 in HaCaT cells,respectively,after 12-hour treatment with NGAL at concentrations of 0 (control group),0.125,0.25,0.5,1 mg/L.Statistical analysis was carried out with SPSS 16 software.by using t test and one-way analysis of variance.Results After 2-week treatment,the PASI score,neutrophil count and NGAL level in children with psoriasis significantly decreased (1.80 ± 1.19,[6.16 ± 0.76] × 109/L,90.86 ± 0.75 μ g/L,respectively) compared with those before the treatment (10.38 ± 3.42,[11.01 ± 2.85] × 109/L,113.48 ± 21.26 μ g/L,respectively;t =31.42,18.34,16.37 respectively,all P ＜ 0.001).Before the treatment,the serum level of NGAL in the patients was positively correlated with the PASI score and peripheral neutrophil count (r =0.918,0.799 respectively,both P ＜ 0.05).The mRNA and protein expression of IL-22 in HaCaT cells significantly differed among these groups treated with different concentrations of NGAL (F =176.31,296.96 respectively,both P ＜ 0.001),so did the mRNA and protein expression of TNF-α (F =193.28,318.80 respectively,both P ＜ 0.001).Additionally,the protein and mRNA expression of IL-22 and TNF-α in HaCaT cells was significantly higher in the 0.125-,0.25-,0.5-and 1-mg/L NGAL group than in the control group (all P ＜ 0.05).The NGAL level was positively correlated with the protein and mRNA expression of TNF-α and IL-22 in HaCaT cells (all P ＜ 0.05).Conclusions The serum level of NGAL was high in children with psoriasis,and positively correlated with severity of skin lesions and peripheral neutrophil count.NGAL can upregnlate the expression of TNF-α and IL-22 in HaCaT cells in vitro.

Expression of serum neutrophil gelatinase-associated lipocalin in children with psoriasis and its pathogenic mechanisms / 中华皮肤科杂志

Objective@#To explore the relationships of neutrophil gelatinase-associated lipocalin (NGAL) with severity of skin lesions in children with psoriasis and peripheral neutrophil count, and to evaluate in vitro effect of NGAL on expression of tumor necrosis factor-α (TNF-α) and interleukin-22 (IL-22) by a human immortalized keratinocyte cell line HaCaT.@*Methods@#From January 1st 2017 to December 31st 2018, 98 children who newly developed psoriasis were enrolled from Department of Dermatology of 6 hospitals in China, including 51 males and 47 females. Their age was 7.00 ± 2.99 years (range: 3-14 years) , and their course of disease was 7.4 ± 5.85 days (range: 3-28 days) . The serum level of NGAL was detected in all the patients before and two weeks after treatment, and the relationships of NGAL with psoriasis area and severity index (PASI) scores and peripheral neutrophil count were evaluated. Western blot analysis and reverse-transcription (RT) -PCR were performed to determine the protein and mRNA expression of TNF-α and IL-22 in HaCaT cells, respectively, after 12-hour treatment with NGAL at concentrations of 0 (control group) , 0.125, 0.25, 0.5, 1 mg/L. Statistical analysis was carried out with SPSS 16 software. by using t test and one-way analysis of variance.@*Results@#After 2-week treatment, the PASI score, neutrophil count and NGAL level in children with psoriasis significantly decreased (1.80 ± 1.19, [6.16 ± 0.76] × 109/L, 90.86 ± 0.75 μg/L, respectively) compared with those before the treatment (10.38 ± 3.42, [11.01 ± 2.85] × 109/L, 113.48 ± 21.26 μg/L, respectively; t = 31.42, 18.34, 16.37 respectively, all P < 0.001) . Before the treatment, the serum level of NGAL in the patients was positively correlated with the PASI score and peripheral neutrophil count (r = 0.918, 0.799 respectively, both P < 0.05) . The mRNA and protein expression of IL-22 in HaCaT cells significantly differed among these groups treated with different concentrations of NGAL (F = 176.31, 296.96 respectively, both P < 0.001) , so did the mRNA and protein expression of TNF-α (F = 193.28, 318.80 respectively, both P < 0.001) . Additionally, the protein and mRNA expression of IL-22 and TNF-α in HaCaT cells was significantly higher in the 0.125-, 0.25-, 0.5- and 1-mg/L NGAL group than in the control group (all P < 0.05) . The NGAL level was positively correlated with the protein and mRNA expression of TNF-α and IL-22 in HaCaT cells (all P < 0.05) .@*Conclusions@#The serum level of NGAL was high in children with psoriasis, and positively correlated with severity of skin lesions and peripheral neutrophil count. NGAL can upregulate the expression of TNF-α and IL-22 in HaCaT cells in vitro.

Urinary Extracellular Vesicle: A Potential Source of Early Diagnostic and Therapeutic Biomarker in Diabetic Kidney Disease / 中华医学杂志(英文版)

<p><b>Objective</b>Diabetic kidney disease (DKD) has become one of the major causes of end-stage renal disease. Urinary extracellular vesicles (uEVs) contain rich biological information which could be the ideal source for noninvasive biomarkers of DKD. This review discussed the potential early diagnostic and therapeutic values of proteins and microRNAs in uEVs in DKD.</p><p><b>Data Sources</b>This review was based articles published in PubMed, Embase, Cochrane, and Google Scholar databases up to November 20, 2017, with the following keywords: "Diabetic kidney disease", "Extracellular vesicle", and "Urine".</p><p><b>Study Selection</b>Relevant articles were carefully reviewed, with no exclusions applied to the study design and publication type.</p><p><b>Results</b>There is no "gold standard" technology to separate and/or purify uEVs. The uEVs contain a variety of proteins and RNAs and participate in the physiological and pathological processes of the kidney. UEVs, especially urinary exosomes, may be useful biomarkers for early diagnosis and treatment to DKD. Furthermore, the uEVs has been used as a therapeutic target for DKD.</p><p><b>Conclusion</b>Proteins and nucleic acids in uEVs represent promising biomarker for the diagnosis and treatment of DKD.</p>

Characterization of a small molecule inhibitor of tumor necrosis factor-alpha production / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Numerous studies have shown that reducing the level of tumor necrosis factor-alpha (TNFα) through the use of anti-TNF antibodies or soluble TNF receptor is a safe and efficacious treatment to inflammatory diseases such as rheumatoid arthritis. Therefore, novel approaches to achieve this outcome are desired. The aim of this study was to investigate the characterization of a small molecule inhibitor, Y316, which blocks TNF mRNA upregulation and TNF production by lipopolysaccharides (LPS) stimulated monocytes.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMC) from healthy volunteers were plated in 24-well plates and stimulated with LPS (1 µg/ml), phorbol-12-myristate-13-acetate (PMA) (100 ng/ml), zymosan (10 µg/ml) and Tsst (100 ng/ml). Supernatants were collected after 4-hour culture at 37°C, and quantitative determination of TNFα, interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and IL-2 production in the supernatants was performed by colorimetric enzyme-linked immunosorbent assay (ELISA). Total RNA of PBMC was isolated and cytokine mRNA quantitation was performed by using a RNA level measuring kit (R & D Systems). PBMC were pretreated with Y316 (10 µmol/L, 1 µmol/L, 0.1 µmol/L, 0.01 µol/L and 0.001 µmol/L) or dimethyl sulfoxide at 37°C for 10 minutes, and then stimulated with LPS or PMA, protein concentrations of p44.42, IKBα, P38 and Jun NH2-terminal kinase were determined by Western blotting. Cyclic adenosine-3',5'-monophosphate (cAMP) of PBMC was measured by enzyme immunoassay kit (Amersham Pharmacia Biotech).</p><p><b>RESULTS</b>Y316 blocked TNF production and inhibited the upregulation of TNF mRNA levels in response to LPS, and also prevented the production of IL-1 and IL-6. In contrast, Y316 augmented the production of IL-10 in LPS-stimulated monocytes. Y316 failed to prevent the production of IL-2 and TNF in antigen-stimulated T cells, suggesting that its effects may be cell-type specific. Y316 prevented the phosphorylation and activation of the MAPK, ERK, and therefore appeared to mediate its effects on TNF by acting at an early point in the signaling cascade induced in response to LPS. There was no effect of Y316 on cAMP levels either alone or in the presence of LPS.</p><p><b>CONCLUSIONS</b>Y316 appears to be a small molecule inhibiting TNF production, which may act via a novel mechanism. Identification of the target of Y316 may lead to the development of alternative strategies for achieving selective cytokine inhibition.</p>

Effects of simvastatin on the mouse model of sclerotic skin / 中华皮肤科杂志

Objective To study the effect of simvastatin on the mouse model of sclerotic skin. Methods A total of 44 mice were divided into two groups, i.e., early administration group (n=24) and post-induction administration group (n=20), and the former was classified into three subgroups, including negative group, model group and simvastatin-treated group, and the latter into two groups, namely blank control group, simvastatin-treated group. The mouse model of sclerotic skin was established by local injec-tions of bleomycin in the back of BALB/c mice. Simvastatin was administered by gavage at a dose of 5 μg per kilogram body weight per day for 4 weeks to mice at the same time when bleomycin was injected in the early group or after 4-week bleomycin injection in the post-induction group. Skin sections were prepared 24 hours after the last administration of simvastatin for histopathological examination and measurement of derma l thickness with HE staining, determination of hydroxyproline content via colorimetry, and mRNA expression of procollagen α1 (Ⅰ) by RT-PCR. Results In the early administration group, a significant increment was observed in the diameter of dermal collagen, skin thickness, and hydroxyproline content in model group compared with the negative control group (all P <0.01), whereas decreased dermal thickness, hydroxyproline content and mRNA expression of procollagen α1(Ⅰ) were noticed in simvastatin-treated group in comparison with the model group (P<0.05, 0.01 and 0.05, respectively). No obvious improvement was achieved in dermal thickness or hydroxyproline content in simvastatin-treated group compared with blank control group (both P0.05), but the mRNA expression of procollagen α1 (Ⅰ) was inhibited in the former group (P<0.05). Conclusion Skin sclerosis is relieved significantly by administration of simvastatin at the induction of scle- rosis but not by that after the induction of sclerotic skin.

Effects of genistein on biological activities of and collagen synthesis by human skin fibroblasts in vitro / 中华皮肤科杂志

Objective To study the effects of genistein on the biological characteristics of and collagen synthesis by human skin fibroblasts in vitro.Methods Human skin fibroblasts(HSFBs)were obtained from the prepuce of healthy adolescents,and suhjected to primary culture.Atier 5 to 15 passages of culture,HSFBs were treated with various concentmtions(0.03125,0.0625,0.125,0.25,0.5,1mg/L)of genistein for different durations.The potential of cell proliferation was detected by MTT assay and growth curves were drawn for HSFBs.Flow cytometry(FCM)and RT-PCR were used to estimate cell cycle phases and mRNA expression of type Ⅰ procollagen.respectively.Results The proliferation rate of HSFBs was 97.7%,113.8%,132.5%,116.4%,94.5%and 83.3%after treatment with genistein of 0.03125,0.0625,0.125,0.25,0.5 and 1 mg/L,respectively.The genistein of more than 0.5 mg/L displayed an inhibitive effect on the proliferation of HSFBs.while that between 0.0625 and 0.25 mg/L showed a promotive effect.Atier treatment with genistein at 0.0625,0.1 25 and 0.25 mg/L,the percentage of HSFBs in S phase and G2 phase significantly increased compared with untreated HSFBs(S phase:41.15%±2.88%,61.89%±3.16%,48.18%±1.68%vs30.12%±0.60%,P＜0.05;G2 phase:9.76%±3.99%,10.40%±0.54%,7.46%±2.47%vs 0.61%±0.16%,P＜0.05).Compared with the untreated HSFBs.the relative mRNA expression level of type Ⅰ procollagen was increased with genistein of 0.0625,0.125 and 0.25 mg/L(0.4814±0.0138,0.5767±0.0291,0.5675±0.0272 vs 0.4101±0.0236,P＜0.01),but decreased with genistein of Ⅰ and 0.5 mg/L(0.1662±0.0165 and 0.2017±0.0203 vs 0.4101±0.0236,P＜0.01).ConclusionCertain concentrations of genistein could enhance the proliferation and growth of as well as mRNA expression of type Ⅰ procollagen in HSFBs.

Amino acid substitution or insertion patterns in penicillin-binding protein 2 in Neisseria gonorrhoeae isolates with reduced susceptibility to ceftriaxone / 中华皮肤科杂志

Objective To investigate the amino acid patterns in penicillin-binding protein 2(PBP2)in Neisseria gonorrhoeae isolates with reduced susceptibility to ceftriaxonc.and the relationship between the amino acid patterns and reduced ceftriaxone susceptibility.Methods DNA was extracted from 13 clinical isolates of N.gonorrhoeae.including 11 strains with decreased susceptibility to ceftriaxone and 2 sensitive isolates.The full-length penA gene encoding the penicillin-binding protein 2 was amplified and sequenced.BLASTn and BLASTx programs were used to assess the insertion and substitution patterns of nucleotides in penA gene and of amino acids in PBP2,respectively.Results BLASTn analysis revealed insertion or substitution of 18-38 nucleotides in the penA gene of gonococcal isolates with reduced ceftriaxone susceptibility.As shown by BLASTX analysis.there were five patterns of amino acid substitution or insertion in PBP2 of the 11 isolates with reduced ceftriaxone susceptibility.However.mosaic structure of PBP2 was not found in any of these isolates.Conclusion Mosaic PBP2 seems not to be the major factor contributing to the decrease in susceptibility of N.gonorrhoeae to ceftriaxone.