Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

OBJECTIVE: To diagnose and fine map a deletion in chromosome region 2q37. METHODS: G-banded chromosomal karyotyping, multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism array (SNP-array), and fluorescence in situ hybridization (FISH) were carried out in conjunct for the analysis. RESULTS: The patient was found to have karyotype of 46,XY,del(2)(q3?), MLPA revealed one copy number of both CAPN10-3 and ATG4B-7 genes from the 2q37.3 region, Both parents were found to be normal upon chromosome karyotyping and MLPA. SNP-array has found a 9.7 Mb deletion in the 2q37.1.37.3 region. FISH analysis has confirmed there is a single copy for 2q37.3. CONCLUSION Combination of MLPA, FISH and SNP-array have enabled accurate diagnosis for the patient, and also provided more clues for the correlation of genotype with the phenotype of the disease, and a basis for genetic counseling.
Chromosome Banding ; Chromosome Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Phenotype

Objective: To investigate the prevalence, awareness, treatment and control status of dyslipidemia among females aged ≥35 years old across China. Methods: Participants were selected by stratified multistage random sampling method in the "Twelfth Five-Year Plan" National Science and Technology Support Project "Survey on the Prevalence of Important Cardiovascular Diseases and Key Technology Research in China" project. This study is a retrospective, cross-sectional study. A total of 17 418 females aged 35 years and over were included in the current study. The basic information such as age, medical history and menopause was collected by questionnaire. The blood lipid parameters were derived from clinical laboratory examinations. The prevalence of dyslipidemia and the rate of awareness, treatment, and control of dyslipidemia were analyzed in females aged 35 years and over. Results: The age of participants was (56.2±13.0) years old, and the prevalence of dyslipidemia was 33.1% (5 765/17 418). The prevalence rates of high total cholesterol, hypertriglyceridemia, low HDL-C and high LDL-C were 9.7% (1 695/17 418), 11.1% (1 925/17 418), 10.9% (1 889/17 418) and 7.3% (1 262/17 418), respectively. The prevalence of dyslipidemia increased with age and the prevalence of dyslipidemia in women who were not married, Han, menarche age>16 years, obesity, central obesity, alcohol consumption, diabetes, hypertension and family history of cardiovascular disease were higher than those without such characteristics (P<0.05). There were 10 432 (59.9%) menopausal females in this cohort and prevalence of dyslipidemia of these participants was 38.8% (4 048/10 432), which was higher than that of non-postmenopausal females (24.6%, 1 717/6 986) (P<0.05). The awareness rates, treatment rates and control rates of dyslipidemia were 33.9% (1 953/5 765), 15.1% (870/5 765) and 2.5% (143/5 765) respectively among females aged 35 years and over in China. Conclusion: The prevalence of dyslipidemia in Chinese females aged 35 years and over is high, and its awareness, treatment, and control rates need to be optimized.
Adult ; Aged ; Cardiovascular Diseases ; China/epidemiology* ; Cross-Sectional Studies ; Dyslipidemias/epidemiology* ; Female ; Humans ; Middle Aged ; Obesity/epidemiology* ; Prevalence ; Retrospective Studies ; Risk Factors

Aim To study the nephrotoxicity effects of the main monomers in Zuojin Pills. Methods CCK-8 and high-content toxicity screening were used to preliminarily screen the main alkaloids in Zuojin Pills that may cause renal cell damage. Further, by confirmation of cell morphology, release rate of lactate dehydrogenase and cytochrome C, and expression of apoptosis-related proteins, the alkaloids causing cell damage were preliminarily identified, providing in vitro toxicological evidence for the compatibility of components of traditional Chinese medicine and compatibility attenuation. Results Preliminary screening using CCK-8 method and high-content technology showed that evodiamine (EVO) could significantly reduce cell number, increase cell membrane permeability, and reduce mitochondrial membrane potential. In addition, cell morphology, apoptosis and cytochrome C expression were consistent with the results of high-content screening. Western blot experiments indicate that EVO could induce apoptosis and cause renal cell damage. Conclusions EVO can obviously cause renal cell damage, and may induce apoptosis by affecting mitochondria, cytochrome C and cell membrane permeability.

Objective To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). Methods A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18^th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. Results Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (r_s = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (r_s = 0.97, P < 0.01) and in placental (r_s = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (r_s = 0.81, P < 0.01). Conclusions Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.

The pathological mechanism of allergic rhinitis (AR) involves hierarchically acute and chronic reactions among antigens, immunocytes, immunoglobulins and inflammatory factors. AR, which is characterized by heterogeneity, reacts differently to the current treatment on diverse individuals. Some patients receive unsatisfying clinical outcomes after the treatment. Chinese herbal medicine has become a frequent option to treat AR because it can improve clinical symptoms with excellent safety. The description of Biqiu in ancient Chinese medical literatures is very similar to the clinical manifestation of AR. The major pathogeneses of Biqiu included infection of wind-cold pathogens, deficiency and cold in the lung, and evil depression into heat and wind. Therefore, in modern traditional Chinese medicine （TCM）, Biqiu is considered as an integration of AR, allergic sinusitis and vasomotor rhinitis. According to the pathogenesis and clinical manifestations of Biqiu (including AR), this disease belongs to wind disease in TCM. But modern TCM focuses on deficiency of internal organs and ignores wind evil in syndrome differentiation, contrary to the fact that wind medicine is always used in treating AR. This even leads to an abnormal phenomenon that clinical studies attach little importance to syndrome differentiation. In this paper, we started from the phenomenon that wind medicine is always used in TCM for AR, considering TCM literatures and the study results of modern therapy for wind diseases, and put forward the ideas as follows: AR belongs to exogenous wind disease in TCM, and wind pathogen is the major pathogen, in clinical syndrome differentiation, we should attach more importance to wind evil, and dispelling wind and eliminating dampness is the key to treatment. Meanwhile, based on the fact that most of the classical prescriptions with good effectiveness for AR originated from Treatise on Febrile Disease, mainly including the wind medicines for treating exogenous diseases, it can be inferred that the wind-dispelling and itch-arresting effects of wind medicines are helpful to alleviate or block the allergic reaction of nasal mucus and achieve the goal of relieving itching and sneezing, and the wind-dispelling and dampness-eliminating effects are helpful to alleviate the edema of nasal mucus and achieve the goal of relieving running nose and nasal obstruction. In modern researches, it is also found that classical prescriptions which take wind medicine as a principle component and wind medicine used in AR treatment have good anti-inflammatory, anti-allergic and immune function adjusting effects. This indicates that dispelling wind and eliminating dampness and the wind medicine treatment under its instruction not only correspond to TCM theory, but also have modern science evidences.

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

Objective: To investigate the effect and mechanism of cinnamaldehyde on the angiogenesis of diabetic retinopathy, and the effect of cinnamaldehyde on vascular endothelial growth factor (VEGF) induced proliferation, migration, tube formation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway of EA.hy 926 cells were observed. Method:EA.hy 926 cells were divided into normal control group, model group (7 μg·L^-1 VEGF), and VEGF+cinnamaldehyde group (60, 90, 120, 150 μmol·L^-1). The methyl thiazolyl tetrazolium (MTT) assay and scratch test were used to observe the effect of cinnamaldehyde on the proliferation and migration of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L^-1 VEGF), and VEGF+cinnamaldehyde group (90, 150 μmol·L^-1). The tube formation experiment was used to observe the effect of cinnamaldehyde on the tube formation of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L^-1 VEGF), VEGF+AG490 group (50 μmol·L^-1), VEGF+cinnamaldehyde group (90 μmol·L^-1), VEGF+cinnamaldehyde group (150 μmol·L^-1), and VEGF+cinnamaldehyde group (150 μmol·L^-1)+AG490 group (50 μmol·L^-1). Western Blot method was used to explore the effect of cinnamaldehyde on the JAK2/STAT3 signaling pathway in EA.hy 926 cells induced by VEGF. Result:Compared with the control group, model group obviously promoted the proliferation and migration of EA.hy 926 cells(P<0.01). Compared with the model group, cinnamaldehyde (60, 90, 120, 150 μmol·L^-1) significantly suppressed VEGF-induced proliferation and migration of EA.hy 926 cells (P<0.01). Compared with the control group, VEGF group could promote the tube formation of EA.hy 926 cells. The number of nodes, junctions, meshes and vascular branches were increased, but with no statistical difference. Compared with the model group, cinnamaldehyde (90, 150 μmol·L^-1) showed an obvious inhibitory effect on the number of nodes, junctions and meshes of tubules (P<0.05, P<0.01).Compared with the control group, the expressions of p-JAK2, p-STAT3, and STAT3 in the model group were significantly increased (P<0.05, P<0.01). Compared with the model group, Cinnamaldehyde (150 μmol·L^-1) significantly reduced the expressions of P-JAK2, P-STAT3, STAT3 proteins (P<0.01). Cinnamaldehyde (90 μmol·L^-1) obviously reduced the expressions of p-STAT3 and STAT3 proteins (P<0.05, P<0.01). Conclusion:Cinnamaldehyde showed a significantly inhibitory effect on the proliferation, migration and tube formation of VEGF-induced EA.hy 926 cells, which was related to the inhibition of the activation of JAK2/STAT3 pathway.

Objective To select the optimum process of granule spray for Tangwang Mingmu Granules, To improve the yield and finished product quality. Methods The effects of the relative density, the type of excipients, the ratio of the extract and the excipient, the inlet temperature-the material temperature, the spray rate and the atomization pressure were selected by single factor and orthogonal test respectively to determine the optimum preparation process. Validation for three batch sample, particle flow, hygroscopicity and other related content of the preparation were studied. Results The optimum spray granulation process of Tangwang Mingmu Granules: the relative density of extract (60 ℃ determination) was 1.15–1.20; the excipient was selected as dextrin; the ratio of dry extract and excipient was 58:42; inlet temperature - material temperature was 90-75 ℃; atomization pressure was 0.12 mPa;spray rate was 10 Hz.Conclusion The preparation technology of Tangwang Mingmu Granules optimized in this study is with high preparation rate, good fluidity and hygroscopicity, which can be used for the preparation of Tangwang Mingmu Granules.

BACKGROUND: Oxidative stress is one of the important mechanisms of postoperative abdominal adhesion. The nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) signal pathway is an important endogenous anti-oxidation stress pathway. Our previous study found that ligustrazine nano-spray can inhibit the formation of postoperative abdominal adhesion in rats, and moreover, ligustrazine has an anti-oxidation effect. OBJECTIVE: To observe the effect of ligustrazine nano-spray on the expression of mRNAs and proteins related to the Nrf2-ARE signal pathway in rats with abdominal adhesion, and to investigate the mechanism by which ligustrazine nano-spray inhibits abdominal adhesion via regulating the Nrf2-ARE signal pathway. METHODS: Sprague-Dawley rats were randomly divided into sham group, model group, ligustrazine group and sodium hyaluronate group. In the sham group, only laparotomy was performed without modeling. In the model group, an abdominal adhesion model was created but no drug was used. In the ligustrazine group, ligustrazine nano-spray was used on the wound before incision suturing. In the sodium hyaluronate group, sodium hyaluronate was applied on the wound before incision suturing. RESULTS AND CONCLUSION: Compared with the model group, ligustrazine nano-spray reduced the levels of reactive oxygen species, tissue inhibitor of matrix metalloproteinase 1, but increased the level of matrix metalloproteinase 9 in the rat serum. The expression of Nrf2 and HO-1 mRNA and proteins was also up-regulated in the ligustrazine group relative to the model group. Therefore, ligustrazine nano-sprays can inhibit abdominal adhesions in rats, and its mechanism may be related to the regulation of Nrf2 and heme oxygenase 1 mRNA and proteins expression and the activation of Nrf2-ARE signaling pathway.