ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus （RSV） infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. Protein-protein interaction （PPI） networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established： 10 as the normal group， and the remaining mice were infected with RSV via slow nasal drip of RSV suspension， with cough induced using capsaicin solution. After modeling， mice were divided into a model group， a Montelukast Sodium group （1 mg·kg^-1·d^-1）， and low， medium， and high dose groups of Sangpi Zhike prescription （4.875，9.75，and 19.5 g·kg^-1·d^-1）， with 10 mice per group. From day 14 after RSV infection， the normal and model groups received saline via gavage， while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin（HE） staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 （ERK1/2） and phosphorylated （p）-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction（Real-time PCR） detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2， p-ERK1/2， p-c-Fos protein levels， and inflammatory cytokines interleukin（IL）-4 and （TNF）-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription， with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF， Fos， and Jun. KEGG enrichment revealed 179 pathways， primarily mitogen-activated protein kinase（MAPK）， cancer， TNF， and IL-17 signaling pathways. Animal experiments showed that， compared to those of the normal group， the lung tissue sections of the model group showed typical inflammatory damage， infiltration of inflammatory cells， rupture of alveolar septa， extensive alveolar fusion， and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased （P<0.01）， and the expression level of ERK1/2 mRNA was significantly elevated （P<0.01）. The levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α along the ERK pathway were significantly increased （P<0.05， P<0.01）. Compared to the model group， Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation， decreased p-ERK1/2/ERK1/2 ratios （P<0.05，P<0.01）， lower ERK1/2 mRNA levels， and downregulated ERK pathway proteins （P<0.05，P<0.01）. ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α on ERK pathway components， thereby mitigating lung and intestinal pathological damage.

GJ-4 is crocin enrichments extracted from Gardenia jasminoides J. Ellis, and our previous studies have shown that GJ-4 significantly improved learning and memory impairment induced by Aβ in mice. Herein, a memory deficit model was developed by injecting okadaic acid (OA) into the lateral ventricle of mice, and the neuroprotection and underlying mechanism of GJ-4 on neuronal injury caused by Tau hyperphosphorylation were investigated. The Animal Care & Welfare Committee, Institute of Materia Medica, CAMS & PUMC has approved all procedures (No.00000318). GJ-4 at different doses was intragastric administration to mice for 16 days. Step-down test and Morris water maze test showed that GJ-4 could significantly improve OA-induced memory impairment in mice, and reduced the loss of Nissl bodies in the hippocampus of mice. GJ-4 could also decrease the phosphorylation level of Tau protein at Ser396, Thr231 and Ser404 via increasing protein phosphatase 2A (PP2A) activity and inhibiting glycogen synthase kinase-3β (GSK-3β) activity. Besides, further researches indicated that GJ-4 could inhibit the level of oxidative stress in the brain of OA mice, reduce neuronal apoptosis and inhibit the neuroinflammation mediated by activation of astrocytes in the hippocampus of mice, and eventually achieve its effects in improving learning and memory impairment in mice. According to these findings, we anticipated that GJ-4 might be a potential therapeutic drug for Alzheimer's disease.

Introduction: Advanced glycation end products (AGEs) formation is due to glycation of lipids, proteins, and nucleic acids. AGEs play a vital role in Diabetes Mellitus (DM) and cardiovascular complications and is enhanced by oxidative stress. Hordeum vulgare (Barley Grass) is a cereal plant of grass family poaceae and has been reported to exhibit antidiabetic and antioxidant characteristics and prevention of cardiovascular disease. Current experiment focused on the evaluation of antioxidant and anti-advanced glycation end products formation effect of Hordeum vulgare water extract. Methods: Free radical scavenging ability of Hordeum vulgare water extract, was evaluated using DPPH, nitric oxide, hydrogen peroxide, lipid peroxidation, FRAP and metal ion chelating. Total phenolic content of Hordeum vulgare was also analysed. In-vitro antiglycation activity was done using BSA-MGO, BSA-Glu. Phytochemical screening was performed to detect the presence of flavonoids, saponins, tannins, steroids and terpenoids. Results: The results showed Hordeum vulgare water extract ameliorated the formation of AGE and scavenge free radical from DPPH, Nitric oxide, hydrogen peroxide, Lipid peroxidation, FRAP and Metal ion chelating. Phytochemicals such as saponins, tannins, flavonoids, steroids and terpenoids were detected in Hordeum vulgare water extract. Conclusion: Hordeum vulgare water extract reveals antiglycation and free scavenging properties.

Introduction: Advanced glycation end product (AGE) is formed by the non-enzymatic glycation, leading to free radicals’ production and high oxidative stress. Accumulation of AGEs is associated with chronic diseases which are correlated with diabetes mellitus. Centella asiatica is a traditional medicinal herb used in Asia with numerous pharmacological effects such as antioxidant, wound healing, neuroprotective, and gastrointestinal treatment. This research was aim to evaluate the antioxidant, antiglycation, and phytochemical analysis of C. asiatica leaves (L.) water extract. Methods: The antioxidant activity of the plant extract was evaluated through 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH) radicals, nitric oxide (NO), and chelating capacity assays. Total phenolic content (TPC) was performed to determine the presence of bioactive compounds, such as saponins, which have been extensively reported in previous studies. Butylated hydroxytoluene (BHT) and ethylenediaminetetraacetic acid (EDTA) were used as positive control in the antioxidant assays, while quercetin was used in the antiglycation assays. Antiglycation effects of C. asiatica L. were evaluated through Bovine serum albumin (BSA)-MGO, BSA-glucose, and MGO scavenging assay. The data was expressed in terms of IC50. Result: The plant extract possessed significantly (p < 0.001) lower IC50 value compared to the BHT in DPPH and NO radical scavenging assay. It also showed stronger antiglycative effect with lower IC50 value compared to the quercetin in BSA-glucose and BSA-MGO assay. The TPC of C. asiatica L. was 3.20 mg/GAE/g at 100µg/ml. Conclusion: The antiglycation effects of C. asiaitca L. include the reduction of Amadori products formation, trapping α-dicarbonyl intermediates, and free radical scavenging. It is suggested that the antiglycation effects of C. asiatica L. maybe attributed by the presence of saponins and other phytochemicals.

OBJECTIVES: This study aimed to investigate the association between periodontal indexes and biomarkers in gingival crevicular fluid (GCF) and preterm birth (PTB) in pregnancy, as well as to assess the clinical value of these indexes as predictors of PTB. METHODS: A nested case-control study was conducted. A total of 300 systematically healthy pregnant women were selected within 36 weeks of gestation and grouped according to the enrolled weeks. Periodontal indexes, including probing depth (PD), bleeding index (BI), gingival index (GI), and five biomarkers in GCF, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured at the enrolled date. The detailed birth outcome was recorded. RESULTS: Only women at 24-28 weeks of gestation per PTB case (four full-term births) were selected as controls subjects, PTB displayed significantly greater GI, BI, and 8-OHdG ( CONCLUSIONS Increased BI and 8-OHdG at 24-28 weeks of gestation are risk factors for PTB. Their combined detection may have some value in the prediction of PTB, but further studies with a larger sample size are needed to explore it and thus provide experiment evidence for establishing an early warning system for PTB in pregnant women with periodontal disease.
Biomarkers ; Case-Control Studies ; Female ; Gingival Crevicular Fluid ; Humans ; Infant, Newborn ; Periodontal Index ; Pregnancy ; Premature Birth

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.
Cell Nucleus ; Doxorubicin ; analogs & derivatives ; chemistry ; Endosomes ; Formates ; chemistry ; Humans ; Liposomes ; chemistry ; MCF-7 Cells ; Microscopy, Confocal ; Particle Size ; Phosphatidylethanolamines ; Polyamines ; chemistry ; Polyethylene Glycols ; chemistry

Objective: To investigate patients' perception of service quality at hospitals in nine Chinese cities and propose some measures for improvement. Methods: The ServQual scale method was used in a survey involving patients at outpatient and in-patient facilities in Shanghai, Chongqing, Chengdu, Nanning, Guilin and Laibin of Guangxi, Honghezhou of Yunnan, Wulumuqi of Xinjiang and Zhongshan of Guangdong. The data collected were entered and analyzed using SPSS 20.0. Statistical analyses included descriptive statistics, factor analyses, reliability analyses, productmoment correlations, independent-sample t-tests, One-way ANOVA and regression analyses. Results: The Kaiser-Meyer-Olkin value for the factor analysis of the scale was 0.979. The Cronbach's α for the reliability analysis was 0.978. All the Pearson correlation coefficients were positive and statistically significant. Visitors to out-patient facilities reported more positive perception than visitors to in-patient facilities on tangibles (t = 4.168, P < 0.001) and reliability (t = 1.979, P < 0.05). Patients of 60 years of age and above reported more positive perception than those between 40 and 49 on reliability (F = 3.311, P = 0.010), assurances (F = 2.751, P < 0.05) and empathy (F = 4.009, P = 0.003). For the five dimensions of the scale, patients in Laibin, Guangxi reported the most positive perceived service quality, followed by patients in Shanghai. On the other hand, patients in Chongqing and Nanning and Guilin of Guangxi reported relatively poor perceptions of service quality. Standardized regression coefficients showed statistically significant (P < 0.001) positive values for all ServQual dimensions. Empathy (β = 0.267) and reliability (β = 0.239) most strongly predicted perception of service quality. Conclusions: Chinese patients perceived service quality as satisfactory. Hospitals in various regions of China should enhance their awareness and ability to serve their patients.