Infiltration and significance of M1 macrophage in breast cancer: an analysis of METABRIC database and clinical validation / 中华肿瘤杂志

Objective: To investigate the differences of immune microenvironment between stage T1N3 and stage T3N0 breast cancer patients and explore the relationship between M1 macrophage infiltration and lymph node metastasis in breast cancer. Methods: Clinical information and RNA-sequencing (RNA-Seq) expression data of stage T1N3 (n=9) and stage T3N0 (n=11) breast cancer patients were extracted from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Using CIBERSORT, the proportions of 22 types of immune cells were calculated, and then the differences of immune cell infiltration between stage T1N3 and T3N0 patients were compared. From 2011 to 2022, pathologic specimens were collected from breast cancer patients who underwent curative resection at the Cancer Hospital, Chinese Academy of Medical Sciences, including 77 at stage T1N3 and 58 at stage T3N0.The METABRIC database analysis results were verified by examining the density of M1 macrophages in tissues using dual-staining immunohistochemistry. Results: METABRIC data analysis showed M1 macrophage was the highest proportion, 15.85% in stage T1N3 breast cancer; M2 macrophage was the highest proportion, 13.07% in stage T3N0 breast cancer.M1 macrophage proportions were statistically different between patients with stage T1N3 and stage T3N0 (P=0.010). The dual-staining immunohistochemistry analysis of breast cancer tissues showed M1 macrophage density (median) of 62.0 and 38.0 cells/mm(2) for stage T1N3 and T3N0, respectively. The difference was statistically significant (P=0.002). Conclusion: The density of M1 macrophages is notably higher in stage T1N3 patients and is associated with lymph node metastasis.

Medicinal evolution and modern research progress on Mume Fructus / 中国中药杂志

Prunus mume is an edible and medicinal material, and Mume Fructus is its processed product, which was first recorded in Shennong's Classic of Materia Medica(Shen Nong Ben Cao Jing). It is an effective drug for stopping diarrhea with astringents and promoting fluid production to quiet ascaris. By consulting the ancient herbal works of the past dynasties, modern codes, and other rela-ted literature, this paper sorted out the medicinal evolution of Mume Fructus, examined the ancient efficacy of Mume Fructus and the main indications, and summarized the inclusion of Mume Fructus in national and provincial standards. It is recorded in the ancient herbal works of the past dynasties that Mume Fructus can be processed by various methods such as roasting, stir-frying or micro-frying, stir-frying with charcoal, single steaming, steaming with wine, and steaming after soaking in wine or vinegar, and prepared into pills, powders, and ointments, which are used in the treatment of fatigue, diabetes, malaria, dysentery, ascariasis, and other diseases. Mume Fructus has been included in nine editions of Chinese Pharmacopoeia and 19 provincial and municipal preparation specifications. The processing method of Mume Fructus is determined, namely, clean P. mume should be softened by moistening in water or steaming and pitted. By reviewing the effects of processing on its chemical composition, pharmacological effects, and its modern clinical application, this paper identified the following issues. The ancient application methods of Mume Fructus are diverse but less commonly used in modern times, there is a lack of standardized research on the processing, and the research on the changes caused by the difference in Mume Fructus before and after processing is not deep. Therefore, it is necessary to further investigate the change pattern of its chemical composition before and after processing and its correlation between its medicinal activity to standardize the processing technology and provide a solid basis for the use of Mume Fructus in parts and its quality control.

Deficiency in glutathione synthesis and reduction contributes to the pathogenesis of colitis-related liver injury / 中南大学学报(医学版)

OBJECTIVES@#Liver disease is the most common extra-intestinal manifestation of ulcerative colitis (UC), but the underlying pathogenesis is still not clarified. It is well accepted that the occurrence of UC-related liver disease has close correlation with immune activation, intestinal bacterial liver translocation, inflammatory cytokine storm, and the disturbance of bile acid circulation. The occurrence of UC-related liver disease makes the therapy difficult, therefor study on the pathogenesis of UC-related liver injury is of great significance for its prevention and treatment. Glutathione (GSH) shows multiple physiological activities, such as free radical scavenging, detoxification metabolism and immune defense. The synthesis and the oxidation-reduction all contribute to GSH antioxidant function. It is reported that the deficiency in hepatic GSH antioxidant function participates in multiple liver diseases, but whether it participates in the pathogenesis of UC-related liver injury is still not clear. This study aims to investigate the feature and underlying mechanism of GSH synthesis and oxidation-reduction function during the development of UC, which will provide useful information for the pathogenesis study on UC-related liver injury.@*METHODS@#UC model was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS)-ethanol solution (5 mg/0.8 mL per rat, 50% ethanol) via intra-colonic administration in rats, and the samples of serum, liver, and colon tissue of rats were collected at the 3rd, 5th, and 7th days post TNBS. The severity degree of colitis was evaluated by measuring the disease activity index, colonic myeloperoxidase activity, and histopathological score, and the degree of liver injury was evaluated by histopathological score and the serum content of alanine aminotransferase. Spearman correlation analysis was also conducted between the degree of colonic lesions and index of hepatic histopathological score as well as serum aspartate aminotransferase level to clarify the correlation between liver injury and colitis. To evaluate the hepatic antioxidant function of GSH in UC rats, hepatic GSH content, enzyme activity of GSH peroxidase (GSH-Px), and GSH reductase (GR) were determined in rats at the 3rd, 5th, and 7th days post TNBS, and the protein expressions of glutamine cysteine ligase (GCL), GSH synthase, GSH-Px, and GR in the liver of UC rats were also examined by Western blotting.@*RESULTS@#Compared with the control, the disease activity index, colonic myeloperoxidase activity, and histopathological score were all significantly increased at the 3rd, 5th, and 7th days post TNBS (all P<0.01), the serum aspartate aminotransferase level and hepatic histopathologic score were also obviously elevated at the 7th day post TNBS (all P<0.05). There was a significant positive correlation between the degree of liver injury and the severity of colonic lesions (P=0.000 1). Moreover, compared with the control, hepatic GSH content and the activity of GSH-Px and GR were all significantly decreased at the 3rd and 5th days post TNBS (P<0.05 or P<0.01), and the protein expressions of GCL, GSH-Px, and GR were all obviously down-regulated at the 3rd, 5th, and 7th days post TNBS (P<0.05 or P<0.01).@*CONCLUSIONS@#There is a significant positive correlation between the degree of liver injury and the severity of colonic lesions, and the occurrence of reduced hepatic GSH synthesis and decreased GSH reduction function is obviously earlier than that of the liver injury in UC rats. The reduced hepatic expression of enzymes that responsible for GSH synthesis and reduction may contribute to the deficiency of GSH synthesis and oxidation-reduction function, indicating that the deficiency in GSH antioxidant function may participate in the pathogenesis of UC related liver injury.

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.

Expression comparison and clinical significance of PD-L1 (22C3) and PD-L1 (SP142) in triple negative breast cancer / 中华肿瘤杂志

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).

Research of cedilanid in the prevention of severe pneumonia complicated with heart failure in infants / 中国医师进修杂志

Objective:To investigate the efficacy and safety of cedilanid in the treatment of severe pneumonia in infants and the value of preventing heart failure.Methods:A total of 80 children with severe pneumonia admitted to Dezhou Maternal and Child Health Hospital from January 2019 to December 2020 were selected and randomly divided into the control group and the observation group, with 40 cases in each group. The control group received comprehensive treatment, while the observation group was treated with cedilanid (0.01 mg/kg, one-time intravenous injection) on the basis of the control group. The efficacy of both groups was observed after 5 d of treatment. The incidence of heart failure, correction time of heart failure, improvement time of symptoms and signs, and length of hospitalization time were compared between the two groups; the inflammatory markers, myocardial markers and arterial blood gas indexes were compared between the two groups before and after the treatment.Results:The total effective rate in the observation group was higher than that in the control group, and the incidence of heart failure in the observation group was lower than that in the control group: 90.0% (36/40) vs. 72.5% (29/40), 32.5%(13/40) vs. 10.0%(4/40), the differences were statistically significant ( χ2 = 4.02, 4.10, P<0.05). The improvement time of symptoms and signs (restlessness elimination, respiratory improvement, heart rate improvement and disappearance of rhonchus in lung) in the observation group were less than those in the control group ( P<0.05). The levels of procalcitonin (PCT) and N-terminal pro-brain natriuretic peptide (NT-ProBNP), myocardial troponin I(cTnI), and creatine kinase isoenzyme (CK-MB) in the observation group after treatment were lower than those in the control group: (6.15 ± 1.03) μg/L vs. (10.85 ± 2.12) μg/L, (112.02 ± 30.09) ng/L vs. (215.39 ± 55.08) ng/L, (0.68 ± 0.17) μg/L vs. (1.12 ± 0.34) μg/L, (19.05 ± 6.11) U/L vs. (28.97 ± 7.82) U/L, P<0.05. The levels of oxygen partial pressure (PaO 2), blood oxygen saturation (SaO 2) and oxygenation index (PaO 2/FiO 2) in the observation group after treatment were higher than those in the control group: (6.15 ± 1.03) μg/L vs. (10.85 ± 2.12) μg/L, (112.02 ± 30.09) ng/L vs. (215.39 ± 55.08) ng/L, (0.68 ± 0.17) μg/L vs. (1.12 ± 0.34) μg/L, (19.05 ± 6.11) U/L vs. (28.97 ± 7.82) U/L, P<0.05. Conclusions:Early application of small dose of cedilanid in infants with severe pneumonia can effectively reduce the occurrence of heart failure, improve the clinical symptoms and blood gas indicators, with significant curative effect, which is worthy of promotion.

Edible Bird's Nest Attenuates Menopause-Related Bone Degeneration in Rats via Increaing Bone Estrogen-Receptor Expression / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanistic basis for the attenuation of bone degeneration by edible bird's nest (EBN) in ovariectomized rats.@*METHODS@#Forty-two female Sprage-Dawley rats were randomized into 7 groups (6 in each group). The ovariectomized (OVX) and OVX + 6%, 3%, and 1.5% EBN and OVX +estrogen groups were given standard rat chow alone, standard rat chow +6%, 3%, and 1.5% EBN, or standard rat chow +estrogen therapy (0.2mg/kg per day), respectively. The sham-operation group was surgically opened without removing the ovaries. The control group did not have any surgical intervention. After 12 weeks of intervention, blood samples were taken for serum estrogen, osteocalcin, and osteoprotegerin, as well as the measurement of magnesium, calcium abd zinc concentrations. While femurs were removed from the surrounding muscles to measure bone mass density using the X-ray edge detection technique, then collected for histology and estrogen receptor (ER) immunohistochemistry.@*RESULTS@#Ovariectomy altered serum estrogen levels resulting in increased food intake and weight gain, while estrogen and EBN supplementation attenuated these changes. Ovariectomy also reduced bone ER expression and density, and the production of osteopcalcin and osteorotegerin, which are important pro-osteoplastic hormones that promote bone mineraliztion and density. Conversely, estrogen and EBN increased serum estrogen levels leading to increased bone ER expression, pro-osteoplastic hormone production and bone density (all P<0.05).@*CONCLUSION@#EBN could be used as a safe alternative to hormone replacement therapys for managing menopausal complications like bone degeneration.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

Background/Aims@#Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. @*Methods@#We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. @*Results@#The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

Background/Aims@#Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. @*Methods@#We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. @*Results@#The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

Mechanism of Gynostemma pentaphyllum in treatment of metabolism associated fatty liver disease based on network pharmacology and molecular docking / 中国中药杂志

The present study explored the mechanism of action of Gynostemma pentaphyllum in the treatment of metabolism associa-ted fatty liver disease(MAFLD) by network pharmacology and molecular docking. The main active components and action targets of G. pentaphyllum were collected from TCMSP. Disease-related targets were obtained from GeneCards, OMIM and TTD, and the common targets of the three databases were screened out, which were converted to the genes with standard names by UniProt. The drug-disease common target genes were obtained through Venn tool and uploaded to STRING for the construction of the protein-protein interaction(PPI) network. Cytoscape was used to construct and analyze the drug-active component-common target-disease network. The gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed on the common targets by DAVID. Pymol was adopted to perform molecular docking of active components and the common targets and predict their binding ability. Twenty-four active components(such as gypenosides, quercetin and sitosterol) of G. pentaphyllum were screened out. Ninety-two targets were obtained and 54 common targets were identified. Key targets included TNF, IL6, PTGS2, TP53, CCL2 and VEGFA. GO analysis on biological processes, molecular functions and cellular components and KEGG pathway analysis were performed, and the results indicated that NF-κB, PI3 K-Akt, TNF and HIF-1 signaling pathways were mainly involved. Molecular docking results showed that gypenosides and quercetin had a strong binding ability to TNF, IL6 and PTGS2. The findings of this study revealed that the therapeutic efficacy of G. pentaphyllum on MAFLD might be achieved by resisting inflammation and oxidative stress and improving insulin resistance, providing ideas and a theoretical basis for the development and application of G. pentaphyllum in the treatment of MAFLD.

Prenatal diagnosis of two cases with 2p15-p16.1 microdeletion syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect chromosomal aberrations in two fetuses with multiple malformation.@*METHODS@#The two fetuses were subjected to chromosomal microarray analysis (CMA) by using Affymetrix CytoScan 750K arrays. The results were analyzed by bioinformatic software.@*RESULTS@#CMA analysis suggested that both fetuses harbored pathogenic copy number variations (CNVs) in the 2p15-16.1 region, which ranged from 255 kb to 257 kb and encompassed the XPO1 and USP34 genes.@*CONCLUSION@#Deletion of the chr2 (61 659 957-61 733 075, hg19) encompassing the XPO1 and USP34 genes may underlie the multiple malformations in the two fetuses.

Antibacterial activity and mechanism of moxifloxacin nanoparticles against drug-resistant Pseudomonas aeruginosa / 药学学报

We prepared moxifloxacin (MXF) loaded nanoparticles by nano-precipitation/self-assembly method, then compared the antibacterial activity of MXF and MXF loaded nanoparticles, and investigated the antibacterial mechanism of MXF loaded nanoparticles against Pseudomonas aeruginosa in vitro. The physicochemical properties such as particle size and zeta potential were investigated by laser particle size analyzer. The in vitro release characteristics were investigated by high performance liquid chromatography (HPLC). The effect of nanoparticles on HBE cells viability was investigated by CCK-8 assay. In addition, the in vitro antibacterial activity was investigated by minimum inhibitory concentration (MIC) assay, biofilm formation assays and transmission electron microscope (TEM) observation, then the antibacterial mechanism was initially explored. The particle size measurement showed that the nanoparticles had a size of 332.5 ± 2.7 nm, a polymer dispersion index (PDI) of 0.125 ± 0.053, a zeta potential of -24.3 ± 1.7 mV, and a uniform particle size distribution, drug loading content was (6.02 ± 1.27) %, encapsulation efficiency was (16.69 ± 1.17) %. The TEM results show that the nanoparticles have a spheroidal structure, and the particle size and distribution are consistent with the particle size measurement results. The nanoparticles can be effectively and rapidly released in phosphate buffer saline (PBS), releasing about 70% in 24 h, and releasing 87% in 72 h, and almost completely releasing the MXF at 120 h. At the same time, compared with moxifloxacin free drug, its MIC value is 8 μg·mL-1, which is 1/2 of MXF solution, and can significantly inhibit the formation of bacterial biofilms. It has well antibacterial activity in vitro and can be targeted to the surface of bacteria to exert its efficacy and improve the antibacterial effect. The moxifloxacin nanoparticles prepared in this study has a uniform particle size distribution, well drug release performance and antibacterial effect, and provides new ideas and strategies for the treatment of bacterial lung infection and the development of new antibacterial nanoformulations.

Influence of maternal chromosomal abnormalities on non-invasive prenatal testing for fetal sex chromosome aneuploidies / 中华医学遗传学杂志

OBJECTIVE@#To study the influence of maternal sex chromosomal abnormalities on the prediction of fetal sex chromosome abnormalities (SCAs) by non-invasive prenatal testing (NIPT).@*METHODS@#Thirty-six pregnant women with a prediction for fetal SCAs by NIPT were verified as false positive after prenatal diagnosis using amniotic fluid samples. With informed consent, these women were subjected to chromosomal karyotyping or copy number variations (CNVs) analysis through high-throughput sequencing.@*RESULTS@#Sex chromosomal abnormalities were found in 8 women, which yielded an abnormal rate of 22.22% (8/36). Among these, 3 had sex chromosome aneuploidies (47, XXX), 4 had sex chromosome mosaicisms, and 1 carried structural chromosomal abnormalities. Reanalysis of the results of NIPT were consistent with the maternal CNVs by large. With the ratio of cffDNA (ChrX)/cffDNA was more than 2, 6 of the eight women were found to harbor sex chromosome abnormalities, and the fetal karyotype was normal. However, with a ratio of less than 2, only 2 of the 38 pregnant women had sex chromosome abnormalities, and 10 of the fetuses were confirmed as positive.@*CONCLUSION@#The presence of maternal sex chromosomal abnormalities can greatly influence the result of NIPT, which may also be an important reason for false prediction for fetal SCAs by NIPT. When NIPT indicates abnormal SCAs, it is necessary to analyze maternal sex chromosomes. The ratio of cffDNA(ChrX)/cffDNA may help to determine the source of abnormal signals.

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins / 中华医学杂志(英文版)

BACKGROUND@#The increased permeability of the blood-brain barrier (BBB) induced by ischemia/hypoxia is generally correlated with alteration of tight junctions (TJs). DL-3-n-butylphthalide (NBP) has been shown to exert neuroprotective effects after ischemic injury. However, few studies have assessed the correlation between NBP and TJs. This study aimed to investigate the potential effect of NBP on the TJ proteins claudin-5, zonula occludens-1 (ZO-1), and occludin during brain ischemia.@*METHODS@#A chronic cerebral hypoperfusion (CCH) Sprague-Dawley rat model was established, and NBP (20, 40, or 80 mg/kg, gavage, once a day) treatment was performed for 14 days. NBP (0.1 or 1.0 μmol/L) pre-treatment was applied to an in vitro hypoxia microvascular endothelial cell model (1% O2, 24 h). BBB permeability was assessed by performing the Evans blue assay. The expressions and localization of claudin-5, ZO-1, occludin, phosphorylated/total protein kinase B (p-Akt/Akt), phosphorylated/total glycogen synthase kinase 3β (GSK-3β)/GSK-3β, and β-catenin/β-actin were evaluated by Western blotting or immunofluorescence. Reactive oxygen species (ROS) generation was measured by flow cytometry analysis. TJ ultrastructure was observed by transmission electron microscopy.@*RESULTS@#In CCH rats, treatment with 40 and 80 mg/kg NBP decreased the Evans blue content in brain tissue (9.0 ± 0.9 μg/g vs. 12.3 ± 1.9 μg/g, P = 0.005; 6.7 ± 0.6 μg/g vs. 12.3 ± 1.9 μg/g, P  0.05). In the hypoxia cell model, NBP pre-treatment improved TJ ultrastructure, decreased intracellular ROS level, and increased the expression of claudin-5 (P < 0.01) and ZO-1 (P < 0.01) in comparison with the corresponding values in the hypoxia group. NBP treatment also elevated the relative expression levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and β-catenin/β-actin in comparison with the corresponding values in the hypoxia group (all P < 0.05).@*CONCLUSION@#NBP improves the barrier function of BBB against ischemic injury by upregulating the expression of TJ proteins, possibly by reducing oxidative stress and activating the Akt/GSK-3β/β-catenin signaling pathway.

Metabolic Characteristics of WBC-deplted RBC suspension during Different Storage Stage in MAP Based on UPLC-MS/MS / 中国实验血液学杂志

OBJECTIVE@#To explore the metabolic characteristics and metabolic markers of WBC-depleted RBCs in MAP preservation solution and to analyzed the metabolic profile of RBC in MAP preservation solution by using metabolomics.@*METHODS@#The changes of metabolitcs in 10 U WBC-depleted RBC suspension at 3-different storage period (D 0, D 14 and D 35) were detected by using the UPLC-MS/MS, the charaeteristic ions and metabolic markers of RBC stored in preservation sblution for 0 d, 14 d and 35 days were analyzed by using the principal component analysis(PCA).@*RESULTS@#The number of characteristic ions in RBC and supernatant extracts detected during the initial, middle and final storage could be clearly distinguiseed. The 5 metabolism-related substamces such as lact-c acid, nicotinamide, glucose, 5-htdroxyproline and malic acid showed statistically significant difference in 3 storage period.@*CONCLUSION@#The UPLC-MS/MS method combined with statistical analysis of multivariate data can be used to study the metabolic characteristics of RBC, the different metabolites of RBC in different storage stages can be used as the potential markers for evaluation of guality of RBC in storag period. The results of this study provide a basis for studing the RBC guality changes in storage period.

Chinese Trauma Surgeon Association for management guidelines of vacuum sealing drainage application in abdominal surgeries-Update and systematic review / 中华创伤杂志(英文版)

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins / 中华医学杂志(英文版)

Background@#The increased permeability of the blood-brain barrier (BBB) induced by ischemia/hypoxia is generally correlated with alteration of tight junctions (TJs). DL-3-n-butylphthalide (NBP) has been shown to exert neuroprotective effects after ischemic injury. However, few studies have assessed the correlation between NBP and TJs. This study aimed to investigate the potential effect of NBP on the TJ proteins claudin-5, zonula occludens-1 (ZO-1), and occludin during brain ischemia.@*Methods@#A chronic cerebral hypoperfusion (CCH) Sprague-Dawley rat model was established, and NBP (20, 40, or 80 mg/kg, gavage, once a day) treatment was performed for 14 days. NBP (0.1 or 1.0 μmol/L) pre-treatment was applied to an in vitro hypoxia microvascular endothelial cell model (1% O2, 24 h). BBB permeability was assessed by performing the Evans blue assay. The expressions and localization of claudin-5, ZO-1, occludin, phosphorylated/total protein kinase B (p-Akt/Akt), phosphorylated/total glycogen synthase kinase 3β (GSK-3β)/GSK-3β, and β-catenin/β-actin were evaluated by Western blotting or immunofluorescence. Reactive oxygen species (ROS) generation was measured by flow cytometry analysis. TJ ultrastructure was observed by transmission electron microscopy.@*Results@#In CCH rats, treatment with 40 and 80 mg/kg NBP decreased the Evans blue content in brain tissue (9.0 ± 0.9 μg/g vs. 12.3 ± 1.9 μg/g, P = 0.005; 6.7 ± 0.6 μg/g vs. 12.3 ± 1.9 μg/g, P < 0.01), increased the expression of claudin-5 (0.79 ± 0.08 vs. 0.41 ± 0.06, P < 0.01; 0.97 ± 0.07 vs. 0.41 ± 0.06, P < 0.01), and elevated the ZO-1 protein level (P < 0.05) in brain microvascular segments in a dose-dependent manner in comparison with the corresponding values in the model group. There was no significant difference in occludin expression (P > 0.05). In the hypoxia cell model, NBP pre-treatment improved TJ ultrastructure, decreased intracellular ROS level, and increased the expression of claudin-5 (P < 0.01) and ZO-1 (P < 0.01) in comparison with the corresponding values in the hypoxia group. NBP treatment also elevated the relative expression levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and β-catenin/β-actin in comparison with the corresponding values in the hypoxia group (all P < 0.05).@*Conclusion@#NBP improves the barrier function of BBB against ischemic injury by upregulating the expression of TJ proteins, possibly by reducing oxidative stress and activating the Akt/GSK-3β/β-catenin signaling pathway.

Influence of different levels of skin pricking test on the short-term efficacy of subcutaneous immunotherapy in allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

To explore the effect of different levels of skin pricking test on short-term efficacy of subcutaneous immunotherapy with allergic rhinitis.Thirty-one AR patients were included in our study.All the patients had received subcutaneous immunotherapy for 1 year.According to the levels of SPT the patients were divided into 3 groups(grade 2,10 persons;grade 3,10 persons and grade 4,11 persons).Of all the patients,the nasal symptoms visual analogue scale(VAS)score,medication score and rhinoconjunctivitis quality of life questionnaire(RQLQ)were investigated both before and after receiving 1 year subcutaneous immunotherapy.The total effective rate of VAS score,RQLQ score and medication score was 61.30%,58.06% and 64.52% respectively,but there was no statistical difference among the 3 groups after 1 year subcutaneous immunotherapy(P=0.573,0.136,0.699,>0.05).This study confirms the short efficacy of subcutaneous immunotherapy in AR patients with different levels of SPT.But the level of SPT was not an objective index for shortterm efficacy of subcutaneous immunotherapy of AR.

Coagulation Properties for Whole Blood Stored at 4℃ / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the coagulation properties the refrigerated whole blood stored at 4℃.</p><p><b>METHODS</b>Ten units of whole blood were obtained from healthy volunteer donors and stored at 4±2℃ for 21 days. Samples were collected on the day after donation and on days 2, 4, 6, 8, 10, 14 and 21 for delection including complete blood count, electrolyte, APTT, PT, Fg, blood coagulation factors, and thromboelastography(TEG).</p><p><b>RESULTS</b>The levels of Hb, WBC, Plt, sodium and potassium in each sample accorded with standard of storing whole blood. The level of Hb, WBC, Plt and Na decreased along with prolonging of storage time, while the K level increased along with prolonging of stored time, APTT and PT prolonged along with prolonging of thored time, PT>17 min at d 21, the Fg level change was no-obvious, The level of factor Ⅴ and Ⅷ decreased more than 50 % of baseline on d 6 and 4 respectively; the levels of factor Ⅱ, Ⅶ, Ⅸ, Ⅹ, Ⅺ, Ⅻ showed decreasing trend, but their levels were less than 40 % of baseline values at d 21. TEG test showed that no abnormalily of R value was found, the abnormal valnes of K and Angle were observed at d 21, the abnormal value of MA was observed at d 14.</p><p><b>CONCLUSION</b>The whole blood stored for 10 days possesses normal coagulation function showing important significance for treatment of hemorrhage from war injury and surgical openation of heart and chest.</p>

Effects of Plasma Lipids and Statins on Cognitive Function / 中华医学杂志(英文版)

<p><b>Objective:</b>Dementia is the fourth most common cause of death in developed countries. The relationship between plasma lipids and cognitive function is complex and controversial. Due to the increasing life expectancy of the population, there is an urgent need to control vascular risk factors and to identify therapies to prevent and treat both cognitive impairment and dementia. Here, we reviewed the effects of plasma lipids and statins on cognitive function.</p><p><b>Data Sources:</b>We searched the PubMed database for research articles published through November 2017 with key words including "plasma lipids," "hyperlipidemia," "hypercholesterolemia," "statins," and "cognition function."</p><p><b>Study Selection:</b>Articles were retrieved and reviewed to analyze the effects of plasma lipids and statins on cognitive function and the mechanisms underlying these effects.</p><p><b>Results:</b>Many studies have examined the relationship between plasma lipids and cognitive function, but no definitive conclusions can be drawn. The mechanisms involved may include blood-brain barrier injury, the influence on small blood vessels in the brain, the influence on amyloid deposition, and a neuroprotective effect. To date, most studies of statins and cognition have been observational, with few randomized controlled trials. Therefore, firm conclusions regarding whether mid- or long-term statin use affects cognition function and dementia remain elusive. However, increasing concern exists that statins may be a causative factor for cognitive problems. These adverse effects appear to be rare and likely represent a yet-to-be-defined vulnerability in susceptible individuals.</p><p><b>Conclusions:</b>The association between plasma lipids and cognition, the mechanism of the influence of plasma lipids on cognitive function, and the association between statins and cognitive function are complex issues and currently not fully understood. Future research aimed at identifying the mechanisms that underlie the effects of plasma lipids and statins on cognition will not only provide important insight into the causes and interdependencies of cognitive impairment and dementia, but also inspire novel strategies for treating and preventing these cognitive disorders.</p>