Application of MXenes in Tumor Therapy / 生物化学与生物物理进展

MXenes is an emerging two-dimensional (2D) material, which was composed of layered transition metal carbides and/or nitrides, have attracted enormous attention in the past decade since their innovative discovery by Gogotsi and Barsoum in 2011. The general formula of MXenes is Mn+1XnTx (n=1-4), where M represents transition metal elements (such as Ti, Nb, Ta, etc.), X represents carbon and/or nitrogen, and Tx represents surface terminations (such as —OH, —F, =O, etc.). In recent years, MXenes have been widely applied in the biological field due to their high biocompatibility, abundant surface groups, good conductivity and photothermal properties. Due to the strong absorption of laser in the near infrared region, strong X-ray attenuation ability and surface easily modified by various molecules or nanoparticles, MXenes have been used as photothermal agents and contrast agents in the tumor therapy and tumor diagnosis. This paper reviews the application of MXenes and MXenes-based composites in tumor therapy and active targeting tumor therapy. According to the modal of action on tumor cells, it was divided into monotherapy, bimodal therapy and trimodal therapy. Among them, the monotherapy mainly used the photothermal properties of MXenes for photothermal therapy, studies have found that MXenes QDs can be used for chemodynamic therapy. In addition, sonodynamic therapy can also be achieved by loading the sonosensitizers on the surface of MXenes. Bimodal therapy and trimodal therapy are mainly used to load anticancer drugs, photosensitizers, metal particles and other substances on the surface of MXenes to achieve combination therapy. In contrast to the limited treatment efficacy and possible side effects arising from monotherapy, the development of bimodal therapy and trimodal therapy may harbor the collective merits of respective individual treatments and give rise to much higher anticancer efficacy at lower dosage of therapeutic agents administered, thus avoiding high-dose-induced side effects. The combined use of multiple treatments displayed superior advantages over monotherapy in producing an improved therapy outcome. According to the modal of entry into tumor cells, it was divided into passive targeting and active targeting. Active targeting therapy was mainly divided into homologous targeting therapy and targeting agents targeting therapy. The strategy of homologous targeting therapy was to coat MXenes with tumor cell membrane and increased the uptake of MXenes by tumor cells. Targeting agents targeting therapy used targeting agents to specifically bind to the receptors on the surface of tumor cells, subsequently, the precise uptake of MXenes by tumor cells was achieved. Finally, the current challenges and future development trends of MXenes in preparation technology and tumor therapy are discussed.

Analysis of conjunctival sac microflora and antibiotic susceptibility testing in adolescents after wearing orthokeratology lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the bacterial flora and antibiotic susceptibility testing of conjunctival sac in adolescents after wearing orthokeratology(OK)lens.METHODS:A total of 101 adolescents aged 8 to 14 who admitted to outpatient department of Xi'an No.1 Hospital from September 2021 to August 2022 were recruited in this cross-sectional observational study. There were 51 cases wearing OK Lens(wearing group)and 50 patients not wearing contact lens(non-lens group), the right eye of all patients was selected into the group. The culture of bacterial flora in conjunctival sac between the two groups were compared, the species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the antibiotic susceptibility testing was carried out for the positive strains cultured in the wearing group.RESULTS:The positive rate of conjunctival sac bacterial cultured in the wearing group and the non-lens group was 68.6%(35/51)and 60.0%(30/50), respectively(P>0.05). In both groups, the bacteria with the highest detection rate were staphylococcus epidermidis and staphylococcus aureus. The sensitivity rates of the strains detected in the wearing group to drugs are as follows: Levofloxacin(98%), Moxifloxacin(98%), Gatifloxacin(98%), Cefuroxime(98%), Cefathiamidine(98%), Rifampicin(98%), Chloramphenicol(96%), Cefoxitin(95%), Clindamycin(80%), Gentamicin(74%), Fusidic acid(72%), Tobramycin(64%), Compound sulfamethoxazole(26%), Mezlocillin(10%), Azithromycin(6%), of which the sensitivity rate of Gram-positive cocci was 100% sensitive to Vancomycin.CONCLUSION:Gram-positive cocci are the main bacteria isolated from conjunctival sac of adolescents after wearing OK Lens. Wearing OK Lens will not significantly increase the positive rate of conjunctival sac bacterial flora. Results of antibiotic susceptibility testing may provide guidance for empirical medication in patients wearing OK lens after eye infection.

Disrupted Maturation of Prefrontal Layer 5 Neuronal Circuits in an Alzheimer's Mouse Model of Amyloid Deposition / 神经科学通报·英文版

Mutations in genes encoding amyloid precursor protein (APP) and presenilins (PSs) cause familial forms of Alzheimer's disease (AD), a neurodegenerative disorder strongly associated with aging. It is currently unknown whether and how AD risks affect early brain development, and to what extent subtle synaptic pathology may occur prior to overt hallmark AD pathology. Transgenic mutant APP/PS1 over-expression mouse lines are key tools for studying the molecular mechanisms of AD pathogenesis. Among these lines, the 5XFAD mice rapidly develop key features of AD pathology and have proven utility in studying amyloid plaque formation and amyloid β (Aβ)-induced neurodegeneration. We reasoned that transgenic mutant APP/PS1 over-expression in 5XFAD mice may lead to neurodevelopmental defects in early cortical neurons, and performed detailed synaptic physiological characterization of layer 5 (L5) neurons from the prefrontal cortex (PFC) of 5XFAD and wild-type littermate controls. L5 PFC neurons from 5XFAD mice show early APP/Aβ immunolabeling. Whole-cell patch-clamp recording at an early post-weaning age (P22-30) revealed functional impairments; although 5XFAD PFC-L5 neurons exhibited similar membrane properties, they were intrinsically less excitable. In addition, these neurons received smaller amplitude and frequency of miniature excitatory synaptic inputs. These functional disturbances were further corroborated by decreased dendritic spine density and spine head volumes that indicated impaired synapse maturation. Slice biotinylation followed by Western blot analysis of PFC-L5 tissue revealed that 5XFAD mice showed reduced synaptic AMPA receptor subunit GluA1 and decreased synaptic NMDA receptor subunit GluN2A. Consistent with this, patch-clamp recording of the evoked L23>L5 synaptic responses revealed a reduced AMPA/NMDA receptor current ratio, and an increased level of AMPAR-lacking silent synapses. These results suggest that transgenic mutant forms of APP/PS1 overexpression in 5XFAD mice leads to early developmental defects of cortical circuits, which could contribute to the age-dependent synaptic pathology and neurodegeneration later in life.

Sea-buckthorn slows down-regulation of CYP 2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway / 中国药理学通报

Aim To explore whether sea-buckthorn slows down-regulation of hepatic cytochrome P450 2C(CYP 2C)in mice with liver injury by BCG vaccine(BCG)-induced via PXR/NF-κB pathway.Methods The mouse model of liver injury was induced by a single tail vein injection of BCG 125 mg·kg-1 for hepatitis B research,and the mice were randomly di-vided into control group,BCG group,BCG+sea-buckthorn granules(SG)group(gavage 50,100,200 mg·kg-1,twice a day),BCG+PCN group(intraper-itoneal injection 100 mg·kg-1,once a day).The levels of serum transaminase and TNF-α and IL-1β in liver tissue were detected by ELISA.The nuclear pro-tein expression NF-κB p65 and the total protein expres-sion of pregnane X receptor(PXR),CYP2C in liver were detected by Western blot.Liver pathological changes were observed by HE staining.Results Sea-buckthorn inhibited overexpression of TNF-α,IL-1βand NF-κB p65,alleviated the down-regulation of CYP2C and PXR protein expression,and improved liv-er pathology and serum transaminase in a dose-depend-ent manner.After intervention with PCN,a mouse specific agonist of PXR,it was similar to the high dose group of SG.Conclusion Sea-buckthorn slows down-regulation of CYP2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway.

Compatibility Rules of Prescriptions Containing Forsythiae Fructus in Dictionary of Traditional Chinese Medicine Prescriptions and Anti-inflammatory Mechanism： An Exploration Based on Data Mining and Network Pharmacology / 中国实验方剂学杂志

Objective:To analyze the compatibility rules of prescriptions containing Forsythiae Fructus based on data mining and explore the anti-inflammatory mechanism of Forsythiae Fructus based on network pharmacology，so as to provide reference for the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines. Method:The prescriptions containing Forsythiae Fructus in the<italic> Dictionary of Traditional Chinese Medicine Prescriptions</italic> were collected，based on which a clinical prescription database was constructed. The Chinese herbs combined with Forsythiae Fructus and the corresponding indications were subjected to frequency statistics，association rule analysis，and complex network analysis using SPSS Statistics 26，IBM SPSS Modeler 18.0，and Gephi 9.2. The active components and targets of Forsythiae Fructus for anti-inflammation were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），BATMAN-TCM，and SEA，and the targets related to anti-inflammation from GeneCards，Online Mendelian Inheritance in Man （OMIM），CTD，and GenCLiP3. Following the analysis of protein-protein interactions （PPI） with STRING，a PPI network was constructed. The enrichment analysis was performed using Metascape，and the active component-anti-inflammation target-signaling pathway network of Forsythiae Fructus was constructed by Cytoscape 3.8.2. Result:According to the inclusion and exclusion criteria，2 245 prescriptions containing Forsythiae Fructus were harvested，involving 512 Chinese herbs，with a total usage frequency of 27 314. The Chinese herbs that were most frequently combined with Forsythiae Fructus （>800 times） were Glycyrrhizae Radix et Rhizoma （1 483 times），Scutellariae Radix （964 times），and Angelicae Sinensis Radix （842 times）. Hence，the herbal pairs "Forsythiae Fructus-Scutellariae Radix" and "Forsythiae Fructus-Angelicae Sinensis Radix" were further explored. The prescriptions containing Forsythiae Fructus could be utilized for the treatment of 29 kinds of diseases，and three representative disease categories including "carbuncle，gangrene，sores and ulcers"，"ophthalmic diseases and syndromes" and "epidemic diseases" are selected for data mining. There were 19 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Lonicerae Japonicae Flos-Angelicae Sinensis Radix" as the core herb combination for "carbuncle，gangrene，sores and ulcers". The clustering analysis revealed one multi-herb clustering group，four herbal pairs，and single herb Lonicerae Japonicae Flos，the complex network analysis four herbal modules，and the factor analysis six common factors. There were 23 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Scutellariae Radix-Angelicae Sinensis Radix" as the core herb combination for "ophthalmic diseases and syndromes". The clustering analysis revealed two multi-herb clustering groups and four herbal pairs，the complex network analysis four herbal modules，and the factor analysis five common factors. There were 28 association rules obtained with "Forsythiae Fructus-Glycyrrhizae Radix et Rhizoma-Menthae Haplocalycis Herba-Lonicerae Japonicae Flos" as the core herb combination for "epidemic diseases". The clustering analysis revealed three multi-herb clustering groups，one herbal pair，and two single herbs Forsythiae Fructus and Glycyrrhizae Radix et Rhizoma，the complex network analysis four herbal modules，and the factor analysis five common factors. As demonstrated by network pharmacology-based analysis，the core anti-inflammation components of Forsythiae Fructus were quercetin，luteolin，and kaempferol，and the core targets were phosphoinositide-3-kinase regulatory subunit 1 （PIK3R1），protein kinase B 1 （Akt1），and epidermal growth factor receptor（EGFR）. The biological pathways were mainly concentrated in proteoglycans in cancer，pathways in cancer，and PI3K/Akt signaling pathway，with such functions as inhibition of transcription factors，regulation of enzyme activity，and inflammation-related gene expression involved. Conclusion:This study employed a variety of data mining techniques to objectively，intuitively，and scientifically uncover the compatibility rules of Forsythiae Fructus in the treatment of high-frequency diseases. It has been found that Forsythiae Fructus is often combined with heat-clearing herbs，tonifying herbs，exterior-releasing herbs，and blood-activating and stasis-resolving herbs for diverse diseases and syndromes. Under the premise of clearing heat and removing toxin，reinforcing healthy Qi and dredging stagnation are also emphasized. According to the degree of internal heat exuberance，the heat-clearing herbs with different merits are combined. This study has revealed the unique advantages of Forsythiae Fructus in the treatment of specific diseases and syndromes as well as its multi-component，multi-target，and multi-pathway mechanisms in anti-inflammation，breaking through the limitations in modern clinical and experimental research of Forsythiae Fructus. These findings are of great significance for guiding the rational clinical application of Forsythiae Fructus and the development of health foods and new Chinese medicines，thus better accelerating the development of Chinese medicine health industry.

Effects of SGLT2i on 24-hour ambulatory blood pressure in patients with type 2 diabetes complicating hypertension: a meta-analysis / 中华心血管病杂志

Objective: To analyze the effects of different types of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on 24-hour ambulatory blood pressure in patients with type 2 diabetes mellitus and hypertension. Method: In this meta-analysis, we searched for randomized controlled trials on the effect of SGLT2i on 24-hour ambulatory blood pressure in patients with type 2 diabetes and hypertension. Three databases, namely PubMed, Web of Science and Cochrane Library, were searched. The search was organized on the concept of 3 conceptual groups: the first group contained terms used to describe SGLT2i, the second group contained terms related to blood pressure, and the third group contained terms used to describe randomized controlled trials. The search time was from the establishment of the database to December 2020. The inclusion and exclusion criteria were formulated in accordance with the requirements of the Cochrane systematic review. According to whether the heterogeneity of the study was significant or not, a random effect model or a fixed effect model were used to conduct the analysis on the impact of different types of SGLT2i on 24-hour ambulatory blood pressure and day and night blood pressure in patients with type 2 diabetes and hypertension. Further subgroup analysis was performed to define potential factors, which might lead to clinical heterogeneity. Results: Seven clinical trials were finally included. The result of the meta-analysis showed that compared with placebo group, SGLT2i could reduce the 24-hour dynamic systolic blood pressure of patients with type 2 diabetes and hypertension by 4.36 mmHg (1 mmHg=0.133 kPa). Reduction was 4.59, 3.74, 5.06, and 3.64 mmHg by canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin respectively; SGLT2i could reduce the 24-hour dynamic diastolic blood pressure of patients with type 2 diabetes and hypertension by 2.20 mmHg, and the reduction was 2.30, 1.22, 2.00, and 2.69 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin respectively. SGLT2i could reduce the daytime systolic blood pressure of patients with type 2 diabetes and hypertension by 5.25 mmHg, and reduction was 5.38, 4.87, 6.00, and 4.37 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, respectively. Simultaneously, SGLT2i could reduce the diastolic blood pressure of patients with type 2 diabetes and hypertension by 2.62 mmHg, and the reduction was 2.56, 2.47, and 2.80 mmHg by canagliflozin, empagliflozin and ertugliflozin, respectively. SGLT2i could reduce the nighttime systolic blood pressure of patients with type 2 diabetes and hypertension by 3.62 mmHg, and the reduction was 2.09, 2.06, 3.92, and 2.45 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, respectively. At the same time, SGLT2i could reduce the nighttime diastolic blood pressure of patients with type 2 diabetes and hypertension by 1.60 and 1.51 mmHg, the reduction was 1.53 and 2.58 mmHg by canagliflozin, empagliflozin and ertugliflozin, respectively. Conclusion: SGLT2i can reduce 24-hour ambulatory blood pressure in patients with type 2 diabetes and hypertension.

Effects of ultrafine particulates on cardiac function in rat isolated heart / 北京大学学报(医学版)

OBJECTIVE@#To evaluate whether ultrafine particulates (UFPs) have direct deleterious effects on cardiac function through activating MAPK signaling.@*METHODS@#Langendorff-perfused Sprague-Dawley rat hearts were randomly divided into 2 groups (n=10/each group). In control group, the rat hearts were perfused with Tyrode's buffer for 40 min; in UFPs-treated group, the hearts were perfused with UFPs at a concentration of 12.5 mg/L. Cardiac function was determined by measuring left ventricular developed pressure (LVDP), left ventricular peak rate of contraction and relaxation (±dp/dtmax) and coronary flow (CF). The levels of malondialdehyde (MDA), superoxide dismutase (SOD), total anti-oxidant capacity (TAOC) were detected in order to evaluate cardiac oxidative stress via the thiobarbituric acid assay, water soluble tetrazolium salt assay and colorimetry, respectively. The expressions of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium were observed using immunohistochemical staining and Western blots.@*RESULTS@#No significant changes in cardiac function were detected before and after the perfusion in control group while UFPs perfused hearts showed a decline in cardiac function in a time-dependent manner (all P < 0.05). In UFPs-treated group, LVDP, +dp/dtmax, -dp/dtmax and CF were statistically reduced from (82.6±2.1) mmHg, (1 624±113) mmHg/s, (1 565±116) mmHg/s, (12.0±0.2) mL/min to (56.8±4.4) mmHg, (1 066±177) mmHg/s, (1 082±134) mmHg/s, (8.7±0.3) mL/min (all P < 0.05), respectively. Furthermore, The comparison between the two groups observed that UFPs perfusion caused a significant decrease in cardiac function at 30 and 40 min compared with the control group (all P < 0.05). At the end of the perfusion, the level of MDA was increased from (0.98±0.14) nmol/L to (1.95±0.18) nmol/L, while SOD and TAOC were reduced from (12.50±1.87) U/mL and (6.83±1.16) U/mL to (6.50 ±1.04) U/mL and (3.67±0.82) U/mL (all P < 0.001) in UFPs group, respectively. In coincidence with these changes, immunohistochemistry and Western blots results showed that the levels of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium significantly increased in UFPs group as compared with control group (all P < 0.05).@*CONCLUSION@#The results of this study demonstrated that the short-term exposure of UFPs to the isolated rat hearts has direct and acute toxic effects on cardiac function, probably related to attenuation of anti-oxidative capacity and activation of MAPK signaling pathways.

Association of non-thyroidal illness syndrome with interleukin-6 and interleukin-10 in critically ill children with sepsis / 中国当代儿科杂志

OBJECTIVE@#To study the incidence rate of non-thyroidal illness syndrome (NTIS) in critically ill children with or without sepsis and the association of NTIS with interleukin-6 (IL-6) and interleukin-10 (IL-10).@*METHODS@#A retrospective analysis was performed on the medical data of 97 children with sepsis (sepsis group) and 80 non-sepsis children with bacterial infection (non-sepsis group). The correlations of IL-6 and IL-10 with the thyroid function parameters triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were analyzed.@*RESULTS@#There were no significant differences in age and sex between the sepsis and non-sepsis groups (P>0.05). Compared with the non-sepsis group, the sepsis group had a significantly higher Sequential Organ Failure Assessment score, a significantly longer length of hospital stay, and a significantly higher rate of use of ventilator (P0.05), but the pooled analysis of the two groups showed that IL-6 level was negatively correlated with T3 and T4 levels (P<0.001).@*CONCLUSIONS@#Children with sepsis have a higher incidence rate of NTIS than those without sepsis. The high level of IL-6 may be associated with the development of NTIS.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China / 生物医学与环境科学（英文）

Objective@#Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.@*Methods@#A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( @*Results@#Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.@*Conclusion@#Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Diagnostic value of optic disc retinal nerve fiber layer thickness for diabetic peripheral neuropathy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#To investigate the value of optic disc retinal nerve fiber layer (RNFL) thickness in the diagnosis of diabetic peripheral neuropathy (DPN).@*METHODS@#Ninety patients with type 2 diabetes, including 60 patients without DPN (NDPN group) and 30 patients with DPN (DPN group), and 30 healthy participants (normal group) were enrolled. Optical coherence tomography (OCT) was used to measure the four quadrants and the overall average RNFL thickness of the optic disc. The receiver operator characteristic curve was drawn and the area under the curve (AUC) was calculated to evaluate the diagnostic value of RNFL thickness in the optic disc area for DPN.@*RESULTS@#The RNFL thickness of the DPN group was thinner than those of the normal and NDPN groups in the overall average ((101.07± 12.40) µm vs. (111.07±6.99) µm and (109.25±6.90) µm), superior quadrant ((123.00±19.04) µm vs. (138.93±14.16) µm and (134.47±14.34) µm), and inferior quadrant ((129.37±17.50) µm vs. (143.60±12.22) µm and (144.48±14.10) µm), and the differences were statistically significant. The diagnostic efficiencies of the overall average, superior quadrant, and inferior quadrant RNFL thicknesses, and a combined index of superior and inferior quadrant RNFL thicknesses were similar, and the AUCs were 0.739 (95% confidence interval (CI) 0.635-0.826), 0.683 (95% CI 0.576-0.778), 0.755 (95% CI 0.652-0.840), and 0.773 (95% CI 0.672-0.854), respectively. The diagnostic sensitivity of RNFL thickness in the superior quadrant reached 93.33%.@*CONCLUSIONS@#The thickness of the RNFL in the optic disc can be used as a diagnostic method for DPN.

Meta-analysis on safety and efficacy of dual antiplatelet therapy combining with proton pump inhibitors for patients after percutaneous coronary intervention / 中华心血管病杂志

Objective@#To analyze the impact of dual antiplatelet (DAPT) therapy combining with or without proton pump inhibitors (PPI) on the main outcomes after percutaneous coronary intervention (PCI).@*Methods@#The PubMed, EMBASE and Cochrane Library were searched for relevant literature and the references obtained from these sources were retrieved manually from inception till September 2017. Inclusion and exclusion criteria were established follow the Cochrane review standard. A total of 977 literatures were included, 193 duplicates were excluded, 74 reviews, case reports, letters and systematic reviews were excluded, 667 literatures were excluded after reading the title and abstract, 34 literatures were excluded due to non-randomized control studies and unrelated outcome indicators, and 9 literatures were finally included with a total of 16 589 patients. RevMan 5.3 software was used to compare the incidence of major adverse cardiovascular events (MACE), cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis, stroke, gastrointestinal bleeding and gastrointestinal events in patients with DAPT combining with or without PPI after PCI.@*Results@#MACE was observed in 8 out of the 9 included literatures, and the results showed that MACE occurred in 561 out of 6 282 patients receiving DAPT combining with PPI therapy and in 951 out of 9 632 patients using DAPT alone (OR=1.15, 95%CI 0.88-1.51, P>0.05). Cardiogenic death was observed in 7 out of the 9 included literatures, and the results showed that cardiogenic death occurred in 172 out of 6 453 patients receiving DAPT combining with PPI treatment and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Recurrent myocardial infarction was observed in 7 out of the 9 included literatures, the results showed 416 out of 6 282 cases in DAPT combining with PPI therapy group experienced recurrent myocardial infarction and 691 out of 9 632 cases in DAPT group experienced recurrent myocardial infarction (OR=1.01, 95%CI 0.89-1.16, P>0.05). Four out of 9 literatures observed revascularization. The results showed that revascularization was performed in 64 out of 2 173 patients receiving DAPT combining with PPI therapy and in 105 out of the 2 770 patients using DAPT alone (OR=1.33, 95%CI 0.55-3.24, P>0.05). All-cause death was observed in 7 out of the 9 included literatures, and the results showed that all-cause death occurred in 172 out of the 6 453 patients in DAPT combining with PPI therapy group and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Three out of the 9 included articles observed stent thrombosis, and the results showed that stent thrombosis occurred in 99 out of 2 997 patients receiving DAPT combining with PPI therapy and in 245 out of the 6 198 patients treated with DAPT (OR=1.07, 95%CI 0.83-1.37, P>0.05). Stroke was observed in 2 out of the 9 included literatures. The results showed that stroke occurred in 5 out of 2 019 patients receiving DAPT combining with PPI therapy, and in 4 out of the 2 033 patients treated with DAPT (OR=1.00, 95%CI 0.29-3.49, P>0.05). Gastrointestinal bleeding was observed in 6 out of the 9 included literatures. The results showed that gastrointestinal bleeding occurred in 26 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 93 out of the 3 506 patients treated with DAPT, gastrointestinal bleeding was significantly lower in the DAPT combining with PPI group than DAPT alone group (OR=0.27, 95%CI 0.17-0.41, P<0.01). Gastrointestinal events were reported in 6 out of the 9 included articles. Similarly, gastrointestinal events were observed in 51 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 190 out of the 3 506 patients treated with DAPT alone, the incidence of gastrointestinal events in the DAPT combined with PPI group was significantly lower than DAPT alone group (OR=0.24, 95%CI 0.14-0.42, P<0.01).@*Conclusions@#The incidence of MACE, cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis and stroke are not affected by DAPT combined with PPI therapy after PCI, while the incidence of gastrointestinal bleeding and gastrointestinal events could be reduced by adding PPI to DAPT in patients undergoing PCI.

Wound Age Estimation by Neutrophil Migration Distance / 法医学杂志

Objective To explore the application of neutrophil migration distance for wound age estimation of skeletal muscles in rats, and to provide methodological basis for follow-up study in future. Methods The skeletal muscle contusion model was established in rats, and the control group and the 2, 4, 6 h post-traumatic groups were set. The law of response of neutrophils that participated in the inflammation after injury was detected by immunohistochemical staining, and the relationship between neutrophil migration distance and injury time was detected by TissueFAXS PLUS software. Results The skeletal muscle was obviously infiltrated with neutrophils 2-6 h after injury. The positive rate of neutrophil was （28.75±0.94）% at 2 h post-traumatic, and reached the peak （45.50±3.63）% at 4 h post-traumatic, then decreased to （31.92±1.56）% at 6 h post-traumatic. The neutrophil migration distances increased with the progress of inflammation, and reached （124.80±12.32） μm, （229.03±21.45） μm and （335.04±16.75） μm at 2 h, 4 h and 6 h, respectively. Conclusion There is a relationship of neutrophil infiltrated number and migration distance and wound age within the 2-6 h after skeletal muscle injury, which could be used for the inference of skeletal muscle wound age.

Improving Asymptomatic Left Ventricular Diastolic Dysfunction in Postmenopausal Hypertensive Women with Metabolic Syndrome: A Prospective, Open-Labeled, Randomized Controlled Trial / 中华医学杂志(英文版)

<p><b>Background</b>Postmenopausal women with metabolic syndrome (MetS) have increased cardiovascular morbidity and left ventricular diastolic dysfunction (LVDD). The various protective effects of astragalus membranaceus (AM) have been described in previous studies. Therefore, this study aimed to evaluate the effects of different doses of AM on diastolic function in postmenopausal hypertensive women with MetS.</p><p><b>Methods</b>This was a prospective, randomized controlled study. The postmenopausal hypertensive patients with MetS were enrolled from Lanzhou University Second Hospital from March 2014 to April 2015. Patients were divided into three groups: control group (received conventional medical treatment), AM Group 1 (received AM capsules at 5 g/d additionally), and AM Group 2 (received AM capsules at 10 g/d additionally). Echocardiographic and clinical characteristics were evaluated before and 12 months after treatment. Quantitative data were analyzed using unpaired t-test, analysis of variance, and multiple linear regression analysis.</p><p><b>Results</b>A total of 154 patients were subjected to final analysis. In the AM Group 2, significant improvements were noted in diastolic function 12 months after treatment than those of the control group, including the early diastolic mitral annular velocity (E'; 0.065 ± 0.007 m/s vs. 0.061 ± 0.008 m/s, P = 0.014), the ratio of the early diastolic mitral peak flow velocity to the late diastolic mitral peak flow velocity (E/A; 0.81 ± 0.05 vs. 0.80 ± 0.06, P = 0.012), the ratio of E' to the late diastolic mitral annular velocity (E'/A'; 0.56 ± 0.12 vs. 0.51 ± 0.13, P = 0.048), and the ratio of the early diastolic mitral peak flow velocity (E) to E' (E/E'; 10.70 ± 1.30 vs. 11.37 ± 1.73, P = 0.031). After treatment, E/E' (10.70 ± 1.30 vs. 11.24 ± 1.56, P = 0.021), deceleration time (DT; 261.49 ± 44.41 ms vs. 268.74 ± 53.87 ms, P = 0.046), and E'/A' (0.56 ± 0.12 vs. 0.52 ± 0.13, P = 0.019) values improved more significantly than those of AM Group 2 before treatment. Besides, waist circumference was positively correlated with E' (r = 0.472; P = 0.003) and E'/A' (r = 0.321; P = 0.047). In addition, the waist-to-hip ratio was a significant predictor of DT (r = 0.276; P = 0.041), E' (r = -0.590; P < 0.001), E/E' (r = 0.454; P = 0.004), and E'/A' (r = -0.377; P = 0.018).</p><p><b>Conclusions</b>Conventional medical plus AM therapy improved diastolic function. Moreover, WC and WHR might be risk factors for LVDD.</p><p><b>Chinese Clinical Trial Register</b>ChiCTR-TRC-11001747. http://www.chictr.org.cn/showprojen.aspx?proj=7798.</p>

Improving Asymptomatic Left Ventricular Diastolic Dysfunction in Postmenopausal Hypertensive Women with Metabolic Syndrome: A Prospective, Open-Labeled, Randomized Controlled Trial / 中华医学杂志(英文版)

<p><b>Background</b>Postmenopausal women with metabolic syndrome (MetS) have increased cardiovascular morbidity and left ventricular diastolic dysfunction (LVDD). The various protective effects of astragalus membranaceus (AM) have been described in previous studies. Therefore, this study aimed to evaluate the effects of different doses of AM on diastolic function in postmenopausal hypertensive women with MetS.</p><p><b>Methods</b>This was a prospective, randomized controlled study. The postmenopausal hypertensive patients with MetS were enrolled from Lanzhou University Second Hospital from March 2014 to April 2015. Patients were divided into three groups: control group (received conventional medical treatment), AM Group 1 (received AM capsules at 5 g/d additionally), and AM Group 2 (received AM capsules at 10 g/d additionally). Echocardiographic and clinical characteristics were evaluated before and 12 months after treatment. Quantitative data were analyzed using unpaired t-test, analysis of variance, and multiple linear regression analysis.</p><p><b>Results</b>A total of 154 patients were subjected to final analysis. In the AM Group 2, significant improvements were noted in diastolic function 12 months after treatment than those of the control group, including the early diastolic mitral annular velocity (E'; 0.065 ± 0.007 m/s vs. 0.061 ± 0.008 m/s, P = 0.014), the ratio of the early diastolic mitral peak flow velocity to the late diastolic mitral peak flow velocity (E/A; 0.81 ± 0.05 vs. 0.80 ± 0.06, P = 0.012), the ratio of E' to the late diastolic mitral annular velocity (E'/A'; 0.56 ± 0.12 vs. 0.51 ± 0.13, P = 0.048), and the ratio of the early diastolic mitral peak flow velocity (E) to E' (E/E'; 10.70 ± 1.30 vs. 11.37 ± 1.73, P = 0.031). After treatment, E/E' (10.70 ± 1.30 vs. 11.24 ± 1.56, P = 0.021), deceleration time (DT; 261.49 ± 44.41 ms vs. 268.74 ± 53.87 ms, P = 0.046), and E'/A' (0.56 ± 0.12 vs. 0.52 ± 0.13, P = 0.019) values improved more significantly than those of AM Group 2 before treatment. Besides, waist circumference was positively correlated with E' (r = 0.472; P = 0.003) and E'/A' (r = 0.321; P = 0.047). In addition, the waist-to-hip ratio was a significant predictor of DT (r = 0.276; P = 0.041), E' (r = -0.590; P < 0.001), E/E' (r = 0.454; P = 0.004), and E'/A' (r = -0.377; P = 0.018).</p><p><b>Conclusions</b>Conventional medical plus AM therapy improved diastolic function. Moreover, WC and WHR might be risk factors for LVDD.</p><p><b>Chinese Clinical Trial Register</b>ChiCTR-TRC-11001747. http://www.chictr.org.cn/showprojen.aspx?proj=7798.</p>

Advance of a representative traditional Tibetan medicine Meconopsis horridula on its phytochemical and pharmacological aspects / 中国中药杂志

Meconopsis horridula is one of alpine plants belonging to family Papaveraceae, mainly distributed in Himalaya Range area. M. horridula is a rare alpine flower, and is a kind of traditional Tibetan medicine, which has been included in more than 40 compound formulae, having efficacies of clearing away heat and alleviating pain, activating blood circulation to remove stasis, traditionally used for the treatment of fractures, injuries, and chest and back pains. Modern research shows that the whole plant of M. horridula contains alkaloids, flavonoids, and terpenes, and its pharmacological activities including antitumor, antivirus and myocardial protection etc. However, due to various factors, the current research of M.horridula still faces many challenges. This paper summaries herein a progress of MH on its ecological resources, traditional uses, and studies on chemical constituents and pharmacological effects, hopefully to provide a useful reference for the ecological protection and applications.

Comparison of the Skin and Skeletal Muscle Contusion in Rats Induced by Blunt Force with Different Heights / 法医学杂志

OBJECTIVES@#To explore the differences in the repair process of skin and skeletal muscle after contusion caused by blunt force attack with different heights.@*METHODS@#Three degrees of contusion were performed on SD rats' right hind limbs by a designed free-dropping device falling from 15, 30 and 50 cm heights, which as a main consideration factor for degree of injury. The repair process of skin and skeletal muscle at 6 h, 24 h, 3 d, 7 d and 13 d after contusion were observed using routine histological methods.@*RESULTS@#Hematoma within skin and/or muscle was found in the rats' hind limbs after contusion with three different heights. The repair processes were similar at 24 h after contusion. However, with the increase of height, the display degree was more obvious. At 3 d after contusion, the RBC of the hemorrhagic region would be decomposed and elapsed in 15 cm contusion group, but for 30 cm contusion group, it delayed to 7 d. At 13 d after contusion, the similar result was found in 15 cm and 30 cm contusion groups, in contrast, the 50 cm contusion group was still in the proliferative phase.@*CONCLUSIONS@#With the increase of height, the occurring rate of hematoma within skin and muscle at the same time increases, and the more serious histological appearance after contusion, including inflammation and proliferation, the longer healing process are observed. According to the results of present study and considering forensic application, the contusion model with 50 cm height （2.58 J/cm²） is recommended as the experimental animal model for the future study of wound age estimation on contusion.

Impact of apolipoprotein E gene polymorphism on cerebral blood flow in patients with mild cognitive impairment / 中华神经医学杂志

Objective To investigate whether apolipoprotein E (APOE) genotype specifically modulates cognition function and cerebral blood flow in patients with amnesic mild cognitive impairment (aMCI) by using pulsed arterial spin labeling (ASL) MR imaging.Methods Eighty-three aMCI subjects and 130 healthy controls (HCs) were recruited through heath screening in community from 2012 to 2014 in our hospital.They all underwent neuropsychological battery assessments,genetic screening and MR imaging.The aMCI subjects included 8 APOE ε2ε3 carriers,46 APOE ε3ε3 carriers and 29 APOE ε3ε4 carriers;however,in HCs,there were 35 APOE ε2ε3 carriers,46 APOE ε3ε3 carriers and 49 APOE ε3ε4/ε4ε4 carriers.Neuropsychological scale was performed in all subjects.ASL data were preprocessed by the ASLtbx toolbox.A voxel-wise two-way ANOVA was performed to examine the main effects of'disease'(MCI) and ‘genotype’ (APOE),and the disease-by-genotype interactions on regional cerebral blood flow (rCBF) maps.Multiple linear regression analysis was performed to examine the relationships between neuropsychological scale scores and rCBF values in brain areas showing significant diagnosis-by-genotype interactions.Results (1) As compared with HCs,the aMCI subjects exhibited significantly higher rCBF values primarily in the left superior and middle frontal gyrus (P＜0.05).APOE ε3ε4/ε4ε4 carriers showed significantly higher rCBF values in the right anterior and posterior cingulate cortex,right ventromedial prefrontal cortex/anterior cingutate than those of A POE ε2ε3 carriers and ε3ε3 carriers,respectively (P＜0.05).Significant disease-by-genotype interactions on rCBF were observed in the left superior frontal gyrus,right ventromedial prefrontal cortex/anterior cingutate and bilateral superior temporal gyrus;as compared with A POE ε2ε3 and A POE ε3ε3 carriers,APOE ε3ε4 carriers had significantly higher rCBF values in the above areas in the aMCI group (P＜0.05).(2) The rCBF values in the right anterior cingulate/medial prefomtal gyrus and superior temporal gyrus of APOE ε3ε4 carriers in aMCI group were negatively correlated with the similarity test scores (r=-0.453,P=0.014;r=-0.497,P=0.006).Conclusions The APOE genotype has disease-specific effects on cerebral perfusion;APOE genotype can specifically regulate cerebral blood perfusion in aMCI subjects.The carriers ofAPOE ε3ε4 genotype in aMCI subjects may maintain their overall cognitive function by increasing lateral ventricle-temporal lobe cerebral blood perfusion.

Risk Factor Analysis of Vascular Cognitive Impairment for In-hospital Atrial Fibrillation Patients / 中国循环杂志

Objective: To explore the incidence and risk factors of vascular cognitive impairment (VCI) for in-hospital atrial fibrillation (AF) patients. Methods: A total of 303 in-hospital AF patients were studied. Based on MMSE score evaluation, the patients were divided into 2 groups: Non-VCI group, n=216 and VCI group, n=87. The incidence of VCI was assessed and different cognitive functions were studied by uni- and multivariate regression analysis. Results: Compared with Non-VCI group, the patients in VCI group had the elder age, higher proportion of CHA2DS2-VASC score ≥ 2, more with persistent/permanent AF, more combining diabetes and heart failure (HF), more had increased systolic blood pressure, mean arterial pressure, pulse pressure, left atrial (LA) diameter and serum creatinine; less male and decreased left ventricular end-diastolic diameter, P<0.05 and P<0.001. The occurrence rate of VCI for in-hospital patients was 40.3％, with age and CHA2DS2-VASC score increasing, the incidence of VCI was elevating and the occurrence rates in female was higher than male, the patients with persistent/permanent AF was higher than paroxysmal AF, P<0.05 and P<0.001. Multiple linear regression analysis showed that age (OR=-0.1135, 95％ CI -0.1708 to -0.0562, P=0.0001), female (OR=-1.2528, 95％ CI -2.2056 to -0.3000, P=0.0105), education [primary school level (OR=3.2193, 95％ CI 1.844-4.5940, P<0.0001),middle school and above level (OR=5.9104, 95％ CI 4.6055-7.2154, P<0.0001)], HF (OR=-1.9357, 95％ CI -3.5522 to-0.3192, P=0.0196), stroke (OR=-1.6349, 95％ CI -2.7517 to -0.5181, P=0.0044) and LA diameter (OR=-0.1252, 95％ CI-0.1962 to -0.0541, P=0.0006) were related to VCI occurrence in hospitalized AF patients. Conclusion: The incidence of VCI was high in hospitalized AF patients; elder age, female, lower education, HF, stroke and enlarged LA diameter were the risk factors for VCI occurrence in AF patients.

Risk Factor Analysis of Vascular Cognitive Impairment for In-hospital Atrial Fibrillation Patients / 中国循环杂志

Objective: To explore the incidence and risk factors of vascular cognitive impairment (VCI) for in-hospital atrial fibrillation (AF) patients. Methods: A total of 303 in-hospital AF patients were studied. Based on MMSE score evaluation, the patients were divided into 2 groups: Non-VCI group, n=216 and VCI group, n=87. The incidence of VCI was assessed and different cognitive functions were studied by uni- and multivariate regression analysis. Results: Compared with Non-VCI group, the patients in VCI group had the elder age, higher proportion of CHA2DS2-VASC score ≥ 2, more with persistent/permanent AF, more combining diabetes and heart failure (HF), more had increased systolic blood pressure, mean arterial pressure, pulse pressure, left atrial (LA) diameter and serum creatinine; less male and decreased left ventricular end-diastolic diameter, P<0.05 and P<0.001. The occurrence rate of VCI for in-hospital patients was 40.3％, with age and CHA2DS2-VASC score increasing, the incidence of VCI was elevating and the occurrence rates in female was higher than male, the patients with persistent/permanent AF was higher than paroxysmal AF, P<0.05 and P<0.001. Multiple linear regression analysis showed that age (OR=-0.1135, 95％ CI -0.1708 to -0.0562, P=0.0001), female (OR=-1.2528, 95％ CI -2.2056 to -0.3000, P=0.0105), education [primary school level (OR=3.2193, 95％ CI 1.844-4.5940, P<0.0001),middle school and above level (OR=5.9104, 95％ CI 4.6055-7.2154, P<0.0001)], HF (OR=-1.9357, 95％ CI -3.5522 to-0.3192, P=0.0196), stroke (OR=-1.6349, 95％ CI -2.7517 to -0.5181, P=0.0044) and LA diameter (OR=-0.1252, 95％ CI-0.1962 to -0.0541, P=0.0006) were related to VCI occurrence in hospitalized AF patients. Conclusion: The incidence of VCI was high in hospitalized AF patients; elder age, female, lower education, HF, stroke and enlarged LA diameter were the risk factors for VCI occurrence in AF patients.

Efficacy and Safety of Different Doses of Tirofiban Combined with Coronary Artery Intervention in Treatment of Non ST-segment Elevation Acute Coronary Syndromes / 现代生物医学进展

Objective:To investigate the efficacy and safety of different doses of tirofiban combined with coronary artery intervention in treatment of Non ST-segment elevation acute coronary syndromes (NST-ASC).Methods:110 cases with NST-ACS from October 2014 to January 2016 in our hospital were chosen and divided into the all dose group and half dose group.The TIMI blood grade before and after treatment,cardiac function before and after treatment for 30 d,major adverse cardiac events and bleeding events,hospitalization expenses and hospitalization days were recorded and compared between two groups.Results:Compared with before treatment,the TIMI 2 grade and 3 grade were obvious decreased,and the left ventricular end diastolic volume (LVEDV),left ventricular end systolic volume (LVESV) after treatment for 30 d were all obvious decreased,while the left ventricular ejection fraction (LVEF) were significant increased,P＜0.05.And the TIMI blood flow grading,LVEDV,LVESV and LVEF before and after treatment in two groups had no significant difference (P＞0.05),and the major adverse cardiac events and hospitalization days of two groups had no significant difference,P＞0.05.While the bleeding events and hospitalization expense of all dose group was obvious higher than those of half dose group,P＜0.05.Conclusions:The half dose group of tirofiban combined with coronary artery intervention in treatment NST-ACS has obvious efficacy,it can decrease the bleeding events and hospitalization expense.