Visualization of nasal powder distribution using biomimetic human nasal cavity model

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition / 中国天然药物

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

Experimental study of Lentinan antagonizes against hepatic lipid deposition induced by sodium arsenite in mice / 公共卫生与预防医学

Objective To investigate the ameliorative effect of Lentinan (LNT) on sodium arsenite (SA)-induced hepatic lipid deposition in mice. Methods C57BL/6 mice were used as the experimental subjects, which were divided into control group, SA-exposed group, LNT + SA-exposed group and LNT control group. Blood and liver tissue samples were collected at the end of the experiment, and serum glutathione transaminase (ALT) and glutathione aminotransferase (AST) levels were detected by enzyme-linked immunosorbent assay (ELISA). A part of liver tissues was stained with hematoxylin-eosin (HE) or oil red O to observe the characteristics of liver pathological damage and lipid deposition, and another part of liver tissues was used to detect triglyceride (TG) and Adiponectin (APN) levels by ELISA. Results Compared with control group or LNT control group, SA-exposed group showed the increased levels of AST and ALT, showing the characteristics of liver histopathological damage and lipid deposition, and the APN level decreased while the TG level increased (P<0.05). Compared with SA-exposed group, the levels of AST and ALT decreased in LNT + SA-exposed group, showing the reduced degree of liver tissue damage and lipid deposition, and APN level upregulated while TG level downregulated (P<0.05). Conclusion Chronic SA exposure induces liver function damage, APN downregulation and lipid deposition in C57BL/6 mice, while LNT intervention leads to the significantly improvement of hepatic damage and lipid deposition, which may be related to the elevated APN level in liver.

Heavy chain deposition disease in a case of clear cell renal cell carcinoma- A jack in the box

Renal cell carcinoma (RCC) is the most common subtype of adult renal tumors, and its detection rate in the early stages has been increased in the dawn of advanced imaging modalities. Nephrectomy is the mainstay of treatment; determination of tumor category and staging is the primary concern of oncopathologists. Non-neoplastic renal parenchyma is overlooked majority of times and thus misses the opportunity to detect concomitant medical renal diseases which also predict the renal outcome in the postoperative era. Although any kind of glomerular or extraglomerular pathology may be encountered, vascular changes in the form of arterionephrosclerosis are the commonest one. Here, we take the opportunity to report an unusual association of heavy chain deposition disease (HCDD) with clear cell subtypes of renal cell carcinoma in a 48-year-old male of Indian ethnicity.

Recent advances of pharmaceutical 3D printing extrusion molding technology / 药学学报

3D printing is an additive manufacturing technology with the help of digital control. Since FDA approved the first 3D printing drug in 2015, its research enthusiasm in the pharmaceutical field has been increasing year by year. In printing technology, fused deposition molding (FDM) and semi-solid extrusion (SSE) are the two most widely used extrusion molding technologies. In this review, recent advances of pharmaceutical 3D printing extrusion molding technology are reviewed from six aspects: mechanism, equipment, pharmaceutical excipients, applications, design and industrialization prospects of extrusion molding technology.

Iron deposition and Parkinson disease / 中华行为医学与脑科学杂志

Iron is an essential metal element for human body. It is involved in many important biological metabolic processes. Iron metabolism in the central nervous system has a strict regulatory mechanism. Iron deposition occurs when the homeostasis of iron metabolism is disrupted, leading to an increase in neuronal iron uptake and a decrease in iron discharge. Aging cells develop specific iron deposition, and excessive iron produce reactive oxygen species, which can damage DNA. Highly reactive aldehydes result in irreversible modification of proteins. Stored proteins were stimulated to release iron, which in turn produces more reactive oxygen species, ultimately leading to iron-mediated cell death and neurological dysfunction. The widely used methods for assessing iron deposition include susceptibility weighted imaging and quantitative susceptibility mapping. Abnormally elevated brain iron deposition has been observed in a variety of central nervous system diseases, especially in Parkinson disease. Iron deposition plays an important role in early diagnosis, differential diagnosis, disease evaluation and monitoring and therapeutic effect evaluation of Parkinson disease. This article reviews the research progress of iron deposition in Parkinson disease.

Effect of a novel phosphodiesterase type 5 inhibitor,CPD1,on unilateral renal interstitial fibrosis caused by ureteric obstruction in mice / 中国药理学通报

Aim To investigate the effects of CPD1,a novel phosphodiesterase 5 inhibitor,on renal pathological phenotype and fibrotic protein expression in renal fibrosis model mice. Methods Male C57BL/6 J mice were divided into three groups randomly(sham group,UUO group and UUO+CPD1 group). Unilateral ureteric obstruction model was constructed by surgery,and CPD1(5 mg·kg-1·d-1)was administered by intragastric administration two hours after the modeling for seven days. HE and Sirius Red staining were used to observe the distribution of tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of fibronectin(FN),α-SMA,collagen-I and kidney injury molecule-1(Kim-1). Results Compared with sham operation group,the renal tubules of mice were dilated and accompanied by a large amount of inflammatory infiltration. Moreover,the expressions of FN,α-SMA,collagen-I and Kim-1 proteins increased significantly(P<0.05)in UUO group. CPD1 treatment improved the kidney structure and decreased the expression of collagen fibers. Furthermore,CPD1 inhibited the expression of FN,α-SMA,collagen-I and Kim-1 markedly(P<0.05). Conclusions Phosphodiesterase 5 inhibitor CPD1 alleviates the progression of renal fibrosis induced by unilateral ureteral obstruction through down-regulating ECM deposition in the extracellular matrix and expression of Kim-1. The specific mechanism remains to be further studied.

Effect and mechanism of p-hydroxybenzaldehyde on experimental intestinal fibrosis / 中国药理学通报

Aim To investigate the effect of p-hydroxybenzaldehyde ( HD) on intestinal fibrosis in mice based on mouse intestinal fibrosis model and in vitro EMT model,and to explore the underlying mechanism Methods HE staining, Masson staining, immunohisto-chemistry ,qPCR, Western blot and other experimental methods were used to verify the effect of HD on intestinal fibrosis in mice and the potential mechanism. Results In vivo experiments showed that compared with the normal group, the DSS-induced intestinal fibrosis model group had shortened colon, increased colon his-topathological score, increased collagen volume fraction, and significantly increased collagen I expression. After treatment with 4, 10, and 25 mg • kg

Effect of Gualou Xiebai Decoction on type II cardiorenal syndrome based on endothelial/epithelial-to-mesenchymal transition and its mechanism / 中国药理学通报

Aim To investigate the protective effects of different doses Gualou Xiebai Decoction (GXD) on type II cardiorenal syndrome (type II CRS) and explore its preliminary mechanisms. Methods The type II cardiorenal syndrome rat model was replicated by li-gating the left anterior descending coronary artery. After 10 weeks of intragastric administration, the cardiac function of the rats in each group was evaluated by echocardiography; serum were collected for biochemical testing; heart and kidney tissue samples were stained with HE and Masson to observe pathological changes. The hydroxyproline content in the heart and kidney was detected. The expression levels of endothelial/epitheli-al-to-mesenchymal transition (EndMT/EMT) related proteins in heart and kidney tissues were detecterd by immunofluorescence double staining

Brain iron deposition increases in the bilateral substantia nigra of patients with medication-overuse headache: a quantitative susceptibility mapping analysis / 南方医科大学学报

OBJECTIVE@#To investigate iron accumulation level over the whole brain and explore the possible neuromechanism of medication-overuse headache (MOH) using quantitative susceptibility mapping (QSM).@*METHODS@#Thirty-seven MOH patients and 27 normal control subjects were enrolled in the study for examinations with both a multiecho gradient echo magnetic resonance (MR) sequence and brain high resolution structural imaging. A voxel-based analysis was performed to detect the brain regions with altered iron deposition, and the quantitative susceptibility mapping values of the positive brain regions were extracted. Correlation analysis was performed between the susceptibility values and the clinical variables of the patients.@*RESULTS@#In patients with MOH, increased susceptibility values were found mainly in the bilateral substantia nigra (SN) (MNI coordinate: 8, -18, -14; -6, -16, -14) as compared with the normal control subjects (P < 0.001), but these alterations in iron deposition were not significantly correlated with the clinical variables of the patients (P > 0.05). The susceptibility value in the left SN had an area under curve (AUC) of 0.734, and at the cut-off value of 0.077, its diagnostic sensitivity was 72.97% and its specificity was 70.37% for distinguishing MOH from normal controls; The susceptibility value in the right SN had an AUC of 0.699 with a diagnostic sensitivity of 72.97% and a specificity of 62.96% at the cut-off value of 0.084.@*CONCLUSION@#Increased iron deposition occurs in the bilateral SN of MOH patients, which provides a new insight into the mechanism of mesocorticolimbic dopamine system dysfunction in MOH. QSM technique can be used as a non-invasive means for quantitative analysis of brain iron deposition in migraine neuroimaging.

Mechanism of TRPC in promoting extracellular matrix deposition of glomerular mesangial cells / 西安交通大学学报(医学版)

【Objective】 To explore the role and mechanism of TRPC in promoting extracellular matrix (ECM) deposition in rat glomerular mesangial cells (HBZY-1). Methods Immunofluorescence staining was performed to observe the distribution and expression of TRPC1 and TRPC6 in HBZY-1 cells. After AngⅡ stimulation, qRT-PCR and Western blotting were used to detect the mRNA and protein expressions of Gαq/PLCβ4/TRPC signaling pathway main proteins and ECM deposition indicators (α-SMA, collagenⅢ and fibronectin). By silencing the expressions of TRPC1 and TRPC6 by RNA interference, the expressions of ECM deposition indicators were detected. Changes in [Ca2+]i influx were determined through Fluo-4AM Ca2+ imaging. 【Results】 Both TRPC1 and TRPC6 were expressed in HBZY-1, and were mainly located in cell membrane and cytoplasm. After AngⅡ stimulation, Gαq/PLCβ4/TRPC signaling pathway was activated, and the mRNA and protein expressions of Gαq, PLCβ4, TRPC1 and TRPC6 were all increased (P<0.05). [Ca2+]i influx also increased (P<0.01), and the mRNA and protein expressions of ECM deposition indicators (α-SMA, ColⅢ and Fn) were upregulated (P<0.05). Silencing the expressions of TRPC1 and TRPC6 by RNA interference led to decreased [Ca2+]i influx (P<0.05), and downregulated mRNA and protein expressions of ECM deposition indicators in HBZY-1 cells (P<0.05). The results suggested that inhibition of TRPC expressions could inhibit AngⅡ induced ECM deposition in HBZY-1 cells, which might be associated with decreased [Ca2+]i influx. 【Conclusion】 TRPC may be a novel therapeutic target of renal fibrosis.

Research progress on surface modification of titanium implants by strontium ions / 口腔疾病防治

@#Traditional titanium implants do not completely meet the clinical requirements because they are bioinert. The surface of titanium implants, modified by strontium ions, can enhance osseointegration and reduce peri-implantitis. In this paper, the biological properties of titanium implant surfaces modified by strontium ions were reviewed. Strontium ions can be coated on the implant surface by hydrothermal treatment, electrochemical deposition, phosphate chemical conversion, flame-spraying, supramolecular self-assembly, magnetron sputtering, laser deposition and alkali etching. Implant surfaces modified by strontium ions can not only promote osteogenesis and early osseointegration but also inhibit bacterial growth and reduce postoperative infections. Even better osseointegration and antibacterial effects can be achieved when strontium ions are incorporated with other elements, such as silver, zinc, gallium, and calcium. However, most of the studies on the use of strontium ion-modified titanium implants are animal experiments and in vitro experiments, and the observation time is short compared with the actual service life of the implants. Thus, the conclusions obtained may be different from the actual clinical application, and the long-term effects need to be studied. In addition, the osteogenic effects of various modification methods also need to be compared. Future research can focus on the following points: ① to find efficient modification methods that can be widely used in the clinic; ②to study how to control the concentration of strontium ions near the implant to exert their biological function and reduce their toxic side effects; and ③ to conduct long-term follow-up clinical trials to observe their osteogenic and antibacterial effects.

Punicalagin inhibits hepatic lipid deposition in obese mice via AMPK/ACC pathway / 中国中药杂志

Hepatic lipid deposition is one of the basic manifestations of obesity, and nowadays pharmacological treatment is the most important tool. Punicalagin(PU), a polyphenol derived from pomegranate peel, is a potential anti-obesity substance. In this study, 60 C57BL/6J mice were randomly divided into a normal group and a model group. After establishing a model of simple obesity with a high-fat diet for 12 weeks, the successfully established rat models of obesity were then regrouped into a model group, an orlistat group, a PU low-dose group, a PU medium-dose group, and a PU high-dose group. The normal group was kept on routine diet and other groups continued to feed the high-fat diet. The body weight and food intake were measured and recorded weekly. After 8 weeks, the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument. Oral glucose tole-rance and intraperitoneal insulin sensitivity were tested. Hemoxylin-eosin(HE) staining was applied to observe the hepatic and adipose tissues. The mRNA expression levels of peroxisome proliferators-activated receptor γ(PPARγ) and C/EBPα were determined by real-time quantitative polymerase chain reaction(Q-PCR), and the mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), anterior cingulate cortex(ACC), and carnitine palmitoyltransferase 1A(CPT1A) were determined by Western blot. Finally, the body mass, Lee's index, serum total glyceride(TG), serum total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) levels were significantly higher and high-density lipoprotein cholesterol(HDL-C) levels were significantly lower in the model group as compared with the normal group. The fat deposition in the liver was significantly increased. The mRNA expression levels of hepatic PPARγ and C/EBPα and the protein expression level of ACC were increased, while the mRNA and protein expression levels of CPT-1α(CPT1A) and AMPK were decreased. After PU treatment, the above indexes of obese mice were reversed. In conclusion, PU can decrease the body weight of obese mice and control their food intake. It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism, which can significantly improve hepatic fat deposition. Mechanistically, PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.

Effects of fiber surface deposited with silicon dioxide films on properties of fiber-reinforced composites / 口腔医学

Objective@#To investigate the effects of fiber surface deposited with silicon dioxide films by atomic layer deposition on properties of dental fiber-reinforced composites.@*Methods @#SiO2 films were deposited on the surface of quartz fiber by atomic layer deposition(ALD). Then the quartz fiber was used to manufacture fiber resin composites, which were divided into four groups: A(no soaking agent removal), B(soaking agent removed), C(soaking agent removed and silanization), and D(soaking agent removed, 600 ALD cycles performed and then silanization). Scanning electron microscopy, water contact angle test, hygroscopicity test, CCK8 test and three-point bending test were used to investigate the properties of fiber resin composites.@*Results@#The surface morphology of the quartz fiber treated by ALD was smooth and had no obvious change compared with that before treatment. Moreover, the quartz fiber showed hydrophobicity after silanization. The results of three-point bending test revealed that the mechanical properties of fiber-resin composites modified by ALD were significantly improved(P<0.05). When viewed by scanning electron microscopy, a good interfacial bonding could be seen between quartz fibers and the resin matrix in Group D. In addition, it was found that Group D had low absorbability, low solubility and good biocompatibility. @*Conclusion@#It is shown that deposition of SiO2 films on the quartz fiber by ALD can significantly enhance the mechanical properties of fiber-reinforced composites.

The properties of ZnO nanofilms on titanium surface by atomic layer deposition / 口腔医学

Objective@#To compare and investigate the physicochemical characteristics and antibacterial effect of ZnO nanofilms prepared by atomic layer deposition(ALD) at different deposition cycles.@*Methods@#According to different ALD cycles, four groups were set up (control group, 300, 600 and 1 200 cycles group). Using DEZn and water as precursors, ZnO nanofilms were prepared by ALD on the surface of pure titanium specimens. Surface morphology of the films was observed by scanning electron microscope (SEM); the element composition and crystal type of the films were observed by energy dispersive spectrometer (EDS) and X-Ray Diffraction (XRD); the hydrophilicity and thickness of the films were detected by water contact angle detector and ellipsometer. The cytotoxicity of the films was evaluated by CCK-8 assay. The antibacterial effect against S. aureus in vitro of the films was evaluated by optical density method.@*Results@#The surface morphology of the films was uniform and compact as shown through SEM. The grain size increased with the increase of the number of ALD cycles. EDS results showed that the films were mainly composed of Zn and O elements. XRD results confirmed that the composition of the films was ZnO. Results of water contact angle showed that the films were hydrophobic. The thickness of the films was nanoscale and there was a linear relationship between the thickness and ALD cycles. All experimental groups showed no cytotoxicity. The 1 200 cycles group showed the highest antibacterial rate of 65.9% and 52.3% at 24 and 48 hours respectively, which was the best among all experimental groups. @*Conclusion@#The ZnO nanofilms prepared by ALD at different cycles on pure titanium surface are uniform and compact. Thickness of the films increases with the increase of ALD cycles. The films have good biocompatibility and anti-S. aureus effect in vitro. The 1 200 cycles group has the best antibacterial effect.

MiR-340 mediates the involvement of high mobility group box 1 in the pathogenesis of liver fibrosis / 中华肝脏病杂志

Objective: To explore the pathogenic mechanism of the miR-340/high mobility group box 1 (HMGB1) axis in the formation of liver fibrosis. Methods: A rat liver fibrosis model was established by injecting CCl(4) intraperitoneally. miRNAs targeting and validating HMGB1 were selected with gene microarrays after screening the differentially expressed miRNAs in rats with normal and hepatic fibrosis. The effect of miRNA expressional changes on HMGB1 levels was detected by qPCR. Dual luciferase gene reporter assays (LUC) was used to verify the targeting relationship between miR-340 and HMGB1. The proliferative activity of the hepatic stellate cell line HSC-T6 was detected by thiazolyl blue tetrazolium bromide (MTT) assay after co-transfection of miRNA mimics and HMGB1 overexpression vector, and the expression of extracellular matrix (ECM) proteins type I collagen and α-smooth muscle actin (SMA) was detected by western blot. Statistical analysis was performed by analysis of variance and the LSD-t test. Results: Hematoxylin-eosin and Masson staining results showed that the rat model of liver fibrosis was successfully established. Gene microarray analysis and bioinformatics prediction had detected eight miRNAs possibly targeting HMGB1, and animal model validation had detected miR-340. qPCR detection results showed that miR-340 had inhibited the expression of HMGB1, and a luciferase complementation assay suggested that miR-340 had targeted HMGB1. Functional experiments results showed that HMGB1 overexpression had enhanced cell proliferation activity and the expression of type I collagen and α-SMA, while miR-340 mimics had not only inhibited cell proliferation activity and the expression of HMGB1, type I collagen, and α-SMA, but also partially reversed the promoting effect of HMGB1 on cell proliferation and ECM synthesis. Conclusion: miR-340 targets HMGB1 to inhibit the proliferation and ECM deposition in hepatic stellate cells and plays a protective role during the process of liver fibrosis.

Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo.@*METHODS@#Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.@*RESULTS@#Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01).@*CONCLUSION@#EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice / 中国中药杂志

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-β1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-β1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-β1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

Predictive factors and prognosis of post-stroke seizures / 中华行为医学与脑科学杂志

Objective:To assess the predictive factors and prognosis of post-stroke seizures.Methods:A total of 315 inpatients with acute anterior circulation cerebral infarction from January 2018 to December 2018 were retrospectively collected, including 95 patients with PSS as observation group and 220 patients without PSS as control group.Clinical characteristics of the patients were recorded, including gender, age, lesion specificity, imaging features, past history, and the time and type of seizures.The Alberta stroke program early CT score (ASPECTS) was used to assess the extent of infarction, the national institutes of health stroke scale (NIHSS) and the modified rankin scale (MRS) were used to assess the severity and prognosis of cerebral infarction.The hemorrhage transformation of cerebral infarction was graded according to the European cooperative acute stroke study Ⅲ(ECASS Ⅲ) classification system.SPSS 21.0 software was used for data analysis.Chi-square test was used for categorical variables and t-test or non-parametric test was used for continuous variables. Results:The observation group had lower ASPECTS scores compared with the control group (5(4, 7), 7 (5, 8)), the presence of atrial fibrillation, hemorrhage transformation, laminar necrosis(LN) and hemosiderin deposition (31.6%, 45.3%, 24.2%, 26.3%) were higher than those of control group (20.9%, 28.2%, 9.1%, 16.4%), and the differences were statistically significant (all P<0.05). In multivariate analysis, ASPECTS score ( OR=0.658, 95% CI=0.556-0.778, P<0.001), hemorrhage transformation ( OR=2.307, 95% CI=1.311-4.059, P=0.004), LN ( OR=2.530, 95% CI=1.250-5.123, P=0.010) and hemosiderin deposition ( OR=2.308, 95% CI=1.201-4.436, P=0.012) were the influencing factors of PSS.Partial secondary generalized seizures was the most common type of seizures, and in this group it accounted for 42.1% (40/95), simple partial seizures and complex partial seizures accounted for 12.6% (12/95)respectively, and generalized seizures accounted for 32.6% (31/95). The mean follow-up time of the two groups was 24.1 months and 24.6 months, respectively.The scores of MRS at the last follow-up and discharge (3(2, 4), 2(1, 4)) of the observation group were better than those of the control group (2(1, 3), 1(1, 3)), and the differences were statistically significant(both P<0.05). Conclusions:PSS after cerebral infarction can affect the prognosis of patients, and the large infarction scope, hemorrhage transformation, LN and hemosiderin deposition are the high risk factors of PSS.

Spray pattern and plume geometry measurement method of nasal spray and its correlation with nasal deposition / 药学学报

Nasal spray can treat local diseases such as rhinitis, it also plays an important role in the treatment of systemic diseases including vaccine immunity. As a drug-device combination product, spray pattern is often used as the quality indicator of nasal spray to ensure its quality, plume geometry can not only be combined with the spray pattern to evaluate the performance of the nasal spray, but also can predict the deposition of the nasal spray in the nasal cavity. This article systematically reviews the definition and measurement methods of the spray pattern and plume geometry of nasal spray and their correlation with nasal deposition behavior. The measurement parameters of spray pattern and plume geometry are defined. The influence of formulation, device and trigger parameters on spray pattern and plume geometry is clarified. The correlation between various parameters and nasal deposition is analyzed. The measurement parameters are classified according to the size and shape of the spray. Plume angle is closely related to the deposition of drugs in the nasal cavity. Jet-like plume with a smaller plume angle can increase the navigation ability of the nasal spray in the curved anatomical structure of the nasal cavity, which is conducive to increase drug deposition. This makes it possible to increase deposition of the nasal spray in the nasal cavity via appropriately increasing viscosity and thixotropy of the nasal spray formulation. This review provides the theoretical basis for the high quality nasal spray product development.