A new pyrazine from Hypecoum erectum L / 药学学报

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo2(OAc)4 induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

Efficacy and safety of ustekinumab in the treatment of moderate to severe plaque psoriasis in Singapore

INTRODUCTION@#Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of both interleukin (IL)-12 and IL-23, and it is approved for the treatment of moderate to severe plaque psoriasis. In this study, we assessed the efficacy and safety of patients receiving ustekinumab for psoriasis.@*METHODS@#This retrospective study included all adults with chronic plaque psoriasis who were prescribed ustekinumab in a tertiary dermatologic centre between December 2009 and December 2015. Efficacy end points included a proportion of patients achieving at least 50% and 75% improvement from baseline psoriasis area and severity index (PASI) and body surface area (BSA) at Weeks 4 and 16.@*RESULTS@#A total of 99 patients were prescribed ustekinumab; 69% of these were Chinese, followed by 15% Indians and 9% Malays. 31 patients had documented PASI scores and 55 patients had documented BSA improvements. In patients with recorded PASI scores, 29 (93.5%) of 31 patients achieved PASI 50, and 21 (67.7%) of 31 achieved PASI 75 at week 16. In patients with recorded BSA, 43 (78.2%) of 55 had at least 50% BSA improvement, and 31 (56.4%) of 55 achieved 75% BSA improvement at 16 weeks. Regarding safety, no patient experienced tuberculosis reactivation. A total of 11 (11%) of 99 patients had latent tuberculosis infection and were treated with prophylactic isoniazid. No patient experienced serious adverse events. No cardiovascular events, cutaneous malignancies or deaths were reported over six years.@*CONCLUSION@#Ustekinumab is safe and efficacious in the treatment of patients with moderate to severe plaque psoriasis in a multiethnic Asian population.

Effects of repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride on executive function in depressed adolescents with non-suicidal self-injury / 中国基层医药

Objective:To investigate the effects of repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride on executive function in depressed adolescents with non-suicidal self-injury.Methods:The clinical data of 120 depressed adolescents with depressive disorders who were admitted to The Second Hospital of Jinhua from August 2021 to July 2022 were retrospectively analyzed. They were randomly assigned to undergo treatment either with paroxetine hydrochloride (control group, n = 60) or repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride (observation group, n = 60). All patients were treated for 2 months. Hamilton Depression Rating Scale-24 (HAMD-24) score, Non-suicidal Self-injury Behavior and Function Scale for Adolescents (ANSSIQ) score, executive function, brain-derived neurotrophic factor, 5-hydroxytryptamine, and clinical efficacy were determined in each group. Results:After treatment, the Hamilton Depression Rating Scale-24 score in the observation group was significantly lower than that in the control group [(15.85 ± 1.08) points) vs. (18.72±1.21) points, t = 13.71, P < 0.001). After treatment, the number of self-injury attacks, number of self-injury impulsions, and the intensity of self-injury thought within 2 weeks in the observation group were significantly lower than those in the control group ( t = 3.42, 3.03, 1.92, all P < 0.05). The scores of the Trail Making Test, Stroop Word test, Stroop Color test, and Stroop Color-Word Interference Test were significantly higher in the observation group than those in the control group ( t = 2.66, 3.33, 3.97, 4.64, all P < 0.01). Brain-derived neurotrophic factor and 5-hydroxytryptamine levels in the observation group were (11.45 ± 1.79) μg/L and (136.68 ± 11.90) μg/L, respectively, which were significantly higher than (9.06±2.21) μg/L and (124.82 ± 10.34) μg/L in the control group ( t = 6.51, 5.83, both P < 0.001). The total response rate in the observation group was significantly higher than that in the control group (91.7% vs. 78.3%, Z = 2.73, P = 0.006). Conclusion:Repetitive transcranial magnetic stimulation combined with paroxetine hydrochloride is highly effective on depressive disorders in adolescents with non-suicidal self-injury. The combined therapy can reduce symptoms, improve executive function and cognitive function, and optimize serological indicators, and thereby deserves the clinical promotion.

A new flavonoid glycoside from Epimedium sagittatum / 药学学报

Fourteen flavonoids were isolated and purified from Epimedium sagittatum by various chromatography techniques such as macroporous adsorbent resin, silica gel, ODS, Sephadex LH-20, HW-40C and semi-preparative HPLC. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as 3′-hydroxy-baohuoside-Ⅱ (1), huazhongilexone-7-O-β-D-glucopyranoside (2), kaempferol-3-O-α-L-rhamnoside (3), baohuoside-Ⅱ (4), icariside-Ⅱ (5), kaempferol 3,7-di-O-α-L-rhamnopyranoside (6), (+)-aromadendrin (7), kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L-rhamnopyranoside (8), sagittatoside A (9), 2″-O-rhamnosyl icariside-II (10), apigenin-7-O-β-D-glucoside (11), quercetin 3-O-β-D-apiofuranoyl-(1→2)-α-L-rhamnopyranoside (12), kaempferol (13), icariin (14). Among them, compound 1 is a new compound, while compounds 2, 6-8, 11, and 12 were isolated from E.sagittatum for the first time.

Isolation and identification of two new compounds from Semen Persicae / 药学学报

Five compounds were isolated from the ethyl acetate fraction of Semen Persicae by using various chromatographic methods, including ODS, Sephadex LH-20, HPLC and semipreparative HPLC. Their structures were identified by 1D-NMR, 2D-NMR, HR-ESI-MS, UV, IR, circular dichroism (CD) and ECD calculation techniques: (2R,3R)-5,7,4′-trihydroxy-3′-methoxy-3-formylflavan-3-ol-5-O-β-D-glucopyranoside (1), (7R,8S)-dihydrodehydrodiconiferyl 6″-benzoyl alcohol-9-O-β-D-glucopyranoside (2), (7R,8S)-dihydrodehydrodiconiferyl alcohol-9-β-O-D-glucopyranosid (3), 2-methoxy-4-(2-propenyl)-phenyl-O-β-D-glucopyranoside (4), 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol (5). Compound 1 and 2 are new compounds, and compounds 3-5 were obtained from Prunus davidiana (Carr.) Franch. for the first time.

Two new terpene glycosides from the Alpiniae Oxyphyllae Fructus / 药学学报

Two undescribed terpene glycosides and two compounds were isolated from the n-butanol fraction of Alpiniae Oxyphyllae Fructus by using various chromatographic methods, including MCI Gel, Sephadex LH-20, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified by spectroscopy methods (1D, 2D NMR, UV, IR, MS, etc.), and the absolute configuration of the compound 1 was determined by ECD calculation and acid hydrolysis. Compounds 1 and 2 are new compound, and compounds 3 and 4 were isolated from Alpiniae Oxyphyllae Fructus for the first time.

Neonatal hydrocephalus: single-center 10-year experiences / 中国新生儿科杂志

Objective:To study the past 10 years' experiences of neonatal hydrocephalus in a single-center.Methods:From January 2010 to December 2019, clinical data of infants with hydrocephalus admitted to Neonatology Department of our hospital were retrospectively analyzed. The infants were assigned into different groups according to gestational age, different etiologies and treatments. Their clinical characteristics and outcomes were compared.Results:A total of 223 infants with hydrocephalus were included. 136 (61.0%) infants were in the preterm group and 87 (39.0%) in the full-term group. The incidence of post-intracranial hemorrhage (ICH) hydrocephalus in preterm infants was significantly higher than full-term infants ( P<0.001). According to the etiologies, 58 infants (26.0%) had congenital hydrocephalus (congenital group), 82 cases (36.8%) developed post-ICH hydrocephalus (ICH group), 48 cases (21.5%) had post-CNS-infection hydrocephalus (infection group) and 35 cases (15.7%) had post-ICH+CNS-infection hydrocephalus (ICH+infection group). The incidences of perinatal asphyxia, neonatal resuscitation and endotracheal intubation within 3 d after birth in the ICH group were significantly higher than the other groups ( P<0.05). Among the four groups, the infection group had the highest incidence of neonatal sepsis, the congenital group had the highest incidence of patent ductus arteriosus and the ICH group had the highest incidence of respiratory diseases (all P<0.05).137 cases (61.4%) received non-surgical therapy, 48 cases (21.5%) had temporary drainage, 37 cases (16.6%) with permanent shunt and 1 case (0.4%) intracranial hematoma removal. The congenital group and ICH group with permanent shunt showed significantly higher rate of improvement than temporary drainage group and non-surgical group ( P<0.001). Conclusions:The main etiologies of neonatal hydrocephalus are ICH and CNS infection. The incidence of post-ICH hydrocephalus in premature infants was quite high. Hydrocephalus of different etiologies have different comorbidities. Maternal and infant care during pregnancy and delivery, prevention of neonatal sepsis and ICH are crucial in the prevention of hydrocephalus. More studies are needed for better treatment.

Alkaloids from fruit of Lycium chinense var. potaninii / 中国中药杂志

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 μmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.

Research progress on application of multi-enzyme-catalyzed cascade reactions in enzymatic synthesis of natural products / 中国中药杂志

As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.

Advances in epigenetic modification genes in rare diseases with abnormal cardiac development / 国际儿科学杂志

Epigenetic modification genes are defined as genes whose products modify the epigenome directly through DNA methylation, histone modification or chromatin remodeling.More and more studies have shown that mutations in epigenetic modification genes are an important etiology of rare diseases with abnormal cardiac development.And these diseases usually affect multiple organs including heart due to the change of epigenetic components.Moreover, children′s lives and health are often threatened by a lack of effective drugs and complex cardiovascular malformations.This article reviews advances in molecule genetics of Tatton-Brown-Rahman syndrome, Kabuki syndrome, Rubinstein-Taybi syndrome, CHARGE syndrome and Sifrim-Hitz-Weiss syndrome, and mainly elaborates the mechanism of cardiovascular malformations caused by mutations in corresponding epigenetic modification genes, providing more comprehensive reference for clinical diagnosis and management.

Chemical constituents from fruits of Cornus officinalis and their anti-Alzheimer's disease activity / 药学学报

Fifteen compounds were isolated from fruits of Cornus officinalis by various chromatographic techniques such as Toyopearl HW-40C, Sephadex LH-20, silica gel, and the semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as neolignan A (1), caffeic acid (2), trans-p-hydroxy cinnamic acid (3), esculetin (4), scopoletin (5), benzyl-7-O-β-D-glucopyranoside (6), tachioside (7), 6-O-(4-hydroxybenzoyl) arbutin (8), 2-(3′,4′-dihydroxyphenyl)-1,3-benzodioxole-5-carboxaldehyde (9), (-)-pinoresinol-4-O-β-D-glucopyranoside (10), (7S,8R)-dihydrodehydrodiconiferyl alcohol-9-O-β-D-glucopyranoside (11), (7S,8R)-dihydrodehydrodiconiferyl alcohol-9′-O-β-D-glucopyranoside (12), (+)-lyoniresinol (13), (+)-isolariciresinol-9-O-β-D-glucopyranoside (14), and isolariciresinol-9′-O-β-D-glucopyranoside (15). Compound 1 was a new compound and named as neolignan A, and compounds 6-9 and 14 were isolated from Cornus officinalis for the first time. Compounds 2, 3 and 15 efficiently alleviated the PC12 cells injury induced by Aβ25-35, suggesting their potential anti-Alzheimer's disease activity.

Advance in role of cilia in the pathogenesis of congenital heart disease / 国际儿科学杂志

Congenital heart disease(CHD)is one of the most common genetic diseases, mainly refers to the abnormal cardiovascular development caused by various abnormal factors during fetal development.Studies have found that the normal development of cardiovascular functional structure requires accurate positioning of the left-right asymmetry.As an essential link in body material metabolism and signal-transducing mechanism, cilia may participate in the pathogenesis of CHD by affecting the distribution of the left-right asymmetry of human organs and tissues during embryonic development.Therefore, a thorough understanding of the role, molecular mechanism, and related regulatory genes of cilia in CHD can provide accurate diagnosis and treatment for clinical work to obtain a better prognosis.Here we review the effects of cilia on the positioning of the left-right asymmetry during embryo development and its role in the pathogenesis of CHD.

A new nucleoside from the Oenothera biennis L / 药学学报

Seven nucleoside compounds were isolated from the Oenothera biennis L. by various chromatographic techniques such as Diaion HP-20, silica gel, Sephadex LH-20, MCI and semi-preparative HPLC. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as 9-(3′-carbonyl methyl)hydroxypurine (1), 1-(3′-carbonyl methyl)purine-6,8-dione (2), N-methyl-2-pyridone-5-carboxamide (3), uracil (4), uridine (5), thymidine (6) and 2′-Ο-methoxy luridine (7). Compound 1 is a new nucleoside and compounds 2-7 were newly isolated from the Oenothera biennis L. Compounds 1-2 can significantly increase the viability of BEAS-2B cells induced by TGF-β1, showing potent anti-pulmonary fibrosis activity.

Effects of Tingli Dazao Xiefei Decoction on the immune inflammation and intestinal flora in asthmatic rats / 药学学报

The study aims to explore the intervention mechanism of Tingli Dazao Xiefei Decoction on asthma from the perspective of immune inflammation and intestinal flora, providing a theoretical basis for guiding clinical medication. The ovalbumin (OVA) asthmatic rat model was established by intraperitoneal injection of OVA sensitization solution and aerosol challenge, and divided into control (CON), model (M), dexamethasone group (DEX, 0.075 mg·kg-1) and Tingli Dazao Xiefei Decoction (TLDZ, 3.5 g·kg-1). Firstly, the effects of Tingli Dazao Xiefei Decoction on asthma symptoms of rats, lung and trachea pathological changes of asthmatic rats were observed by inducing cough and asthma experiment, phenol red excretion, hematoxylin-eosin staining (H&E), Masson and periodic acid Schiff (PAS) staining; the levels of transforming growth factor β1 (TGF-β1), interleukin (IL) 6 and IL-10 in rat serum and the levels of interferon γ (IFN-γ), immunoglobulin E (IgE), IL-4, IL-17A and tumor necrosis factor α (TNF-α) in bronchoalveolar lavage fluid (BALF) were detected by ELISA; the mRNA levels of IL-5, IL-13 and IL-33 in the lung were determined by qRT-PCR; the levels of macrophages and neutrophils in the spleen and the levels of natural killer cell (NK), helper T cell (Thc), dendritic cell (DC), regulatory T cell (Treg) and T helper cell 17 (Th17) in the peripheral blood were measured by flow cytometry combined with immunohistochemistry; the intestinal flora of asthmatic rats were analyzed by 16S rDNA high-throughput sequencing. Pathology and inflammatory results showed that Tingli Dazao Xiefei Decoction could effectively alleviate the asthma symptoms in rats, improve the pathological changes of lung tissue, reduce the production of goblet cells and collagen fibers, and reduce the inflammatory response in asthmatic rats; the results of immune cells showed that Tingli Dazao Xiefei Decoction could effectively increase the levels of NK, Thc, DC and Treg cells and reduce the levels of macrophages, neutrophils and Th17 cells in asthmatic rats; the results of intestinal flora showed that Tingli Dazao Xiefei Decoction could increase the levels of Lactobacillus, Ruminococcus, Christensenellaceae, Bifidobacterium and Eubacterium]_xylanophilum-group, and decrease the levels of Firmicutes, Desulfovibrio, Mucispirillum and Romboutsia in asthmatic rats. Therefore, it is speculated that Tingli Dazao Xiefei Decoction can improve the symptom of asthmatic rats by regulating the immune inflammation and intestinal flora in the asthmatic rats. All animal experiments in this article were approved by the Ethics Committee of Henan University of Chinese Medicine.

Berberine alleviates programmed necrosis of metabolic-associated fatty liver disease via activating Nrf2 pathway in mice / 中华肝脏病杂志

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.

A new diterpenoid acid from the rosin of Pinus kesiya var. langbianensis (A.Chev.) Gaussen ex Bui / 药学学报

One undescribed diterpenoid acid and six compounds were isolated from the 95% ethanol fraction of Pinus kesiya var. langbianensis (A.Chev.) Gaussen ex Bui resin by using various chromatographic methods, including MCI Gel, Sephadex LH-20, ODS, silica gel and semi-preparative HPLC. The planar structures were identified by spectroscopy methods (1D, 2D NMR, UV, IR, MS, etc.), and the absolute configuration of the new compound was determined by ECD calculation. Compound 1 is a new compound, and compounds 2, 5-7 were isolated from Pinus kesiya var. langbianensis (A.Chev.) Gaussen ex Bui for the first time.

Active components of Descurainia sophia improve lung permeability in rats with allergic asthma by regulating airway inflammation and epithelial damage / 中国中药杂志

The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.

Novel transdermal device for delivery of triamcinolone for nail psoriasis treatment

INTRODUCTION@#Nail psoriasis treatment is challenging due to difficult drug delivery and systemic therapy toxicities. Self-dissolvable microneedle patches embedded with corticosteroids offers a potentially rapid, minimally invasive drug delivery platform with good efficacy and minimal adverse side effects.@*METHODS@#We conducted a 4-month prospective randomised controlled trial. Subjects with psoriatic nails were randomised to receive microneedle device delivered topical steroids on one hand and control treatment (topical Daivobet gel) on the other. Two independent dermatologists blinded to the treatment assignment scored their Nail Psoriasis Severity Index (NAPSI) during visits at baseline, 2 and 4 months. All treatment was discontinued after 2 months. Average NAPSI score on each hand was analysed.@*RESULTS@#A total of 25 participants were recruited, aged 22 to 73 years. Majority were Chinese (72%), followed by Indian and Malay. There was equal randomisation of treatment to the left and right nail. While there was a rapid significant improvement in average NAPSI score for the control arm at 2 months, the treatment arm had a greater, more sustained improvement of the NAPSI score at 4 months. The average NAPSI score improved for both treatment and control group at 4 months compared to baseline. However, only the NAPSI value improvement in the controls at 2 months compared to baseline was statistically significant (P=0.0039). No severe adverse effects were reported.@*CONCLUSION@#To the best of our knowledge, this is the first prospective randomised control trial comparing microneedle technology against conventional topical steroids in nail psoriasis treatment. Our findings demonstrate microneedle technology is as efficacious as topical therapy.

Research progress of long non-coding RNA in congenital heart disease / 国际儿科学杂志

Congenital heart disease is one of the most common birth defects, which is the main cause of death in children.Cardiovascular development is a complex process involving multiple genes, signaling pathways and regulatory factors.According to the sequencing of human genome and encode project, more than 80% of the genes in the genome are transcribed, but only 3% of these transcripts correspond to protein-encoding RNA.It is pointed out that non-coding RNA is as important or even more important as encoding RNA.More and more evidences show that not only encoding genes are involved in the regulation of cardiovascular development, but also protein non-coding genes play an important role in the development of heart.This review will summarize the biological characteristic and function of long noncoding RNAs, and introduce the role of some representative lncRNA in heart development and congenital heart disease.

Long non-coding RNA SAP30-2:1 is downregulated in congenital heart disease and regulates cell proliferation by targeting HAND2 / 医学前沿

Congenital heart disease (CHD) is the most common birth defect worldwide. Long non-coding RNAs (lncRNAs) have been implicated in many diseases. However, their involvement in CHD is not well understood. This study aimed to investigate the role of dysregulated lncRNAs in CHD. We used Gene Expression Omnibus data mining, bioinformatics analysis, and analysis of clinical tissue samples and observed that the novel lncRNA SAP30-2:1 with unknown function was significantly downregulated in damaged cardiac tissues from patients with CHD. Knockdown of lncRNA SAP30-2:1 inhibited the proliferation of human embryonic kidney and AC16 cells and decreased the expression of heart and neural crest derivatives expressed 2 (HAND2). Moreover, lncRNA SAP30-2:1 was associated with HAND2 by RNA immunoprecipitation. Overall, these results suggest that lncRNA SAP30-2:1 may be involved in heart development through affecting cell proliferation via targeting HAND2 and may thus represent a novel therapeutic target for CHD.