Objective: To evaluate the safety and efficacy of preoperative autologous blood donation (PABD) under anesthesia monitoring in elective surgical procedures, and to provide scientific data for promoting its clinical application. Methods: 1) A total of 1 164 patients scheduled for elective surgery and met the criteria for stored autologous blood transfusion in our hospital from March 2022 to September 2023 were enrolled. Prior to surgery, stored autotransfusion was performed under anesthesia monitoring. During the operation, blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO ) and other basic life indicators before and after blood collection were recorded and analyzed. Adverse reactions during blood collection were documented, and potential influencing factors were analyzed. 2) The autologous transfusion group (experimental group, patients receiving intraoperative autologous blood reinfusion) was compared with the allogeneic transfusion group (control group, patients without PABD during the same period) using propensity score matching. The length of hospital stay, transfusion-related costs, perioperative hemoglobin (Hb), hematocrit (Hct), platelet count (Plt) and coagulation function were compared between the two groups after matching. Results: 1) Three patients (0.26%) had adverse reactions during blood collection. Autologous blood transfusion was performed in 443 patients (38.1%) during or after operation, with no adverse reaction during blood transfusion. 2) The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of patients after blood collection were lower than before blood collection, and the SpO was higher than before blood collection, with statistically significant differences (P<0.05); There was no significant difference in heart rate before and after blood collection (P>0.05); Our analysis found that age, gender, blood collection volume, department, or mild-to-moderate circulatory system complications didn’t significantly affect BP, HR and SpO fluctuations (P>0.05). 3) The experimental group had shorter hospital stays and lower transfusion costs than the control group (P<0.05). 4) No significant differences were observed in Hb, Hct, Plt levels or coagulation function (PT, APTT) between the two groups after operation (P>0.05). The hospitalization duration and transfusion related expenses in the experimental group were lower than those in the control group (P<0.05). Conclusion: PABD under anesthesia monitoring is safe and feasible in elective surgeries across diverse patient groups and surgical fields. It reduces the costs and conserves blood resources, which is worthy of further promotion.

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

Objective·To explore the effects and possible molecular mechanisms of nanoplastics(NPs)on severe asthma.Methods·A mouse model of severe asthma was established by using house dust mite(HDM)and lipopolysaccharide(LPS)co-stimulation.Polystyrene nanoplastics(PS-NPs)were instilled into the severe asthma mice's airways.Subsequently,bronchoalveolar lavage fluid(BALF)was collected and lung tissue sections were prepared.Flow cytometry,hematoxylin-eosin(H-E)staining,periodic acid-Schiff(PAS)staining,immunohistochemistry,and terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining,were used to observe the effects of PS-NPs on airway inflammation,mucus secretion,alveolar structure,and the proliferation and apoptosis of alveolar type Ⅱ epithelial cells(AT2 cells)in severe asthma mice.The CCK-8 assay and Annexin Ⅴ/PI double staining were performed to evaluate the effects of PS-NPs on the proliferation and apoptosis of the mouse AT2 cell line MLE-12.DNA damage in AT2 cells caused by PS-NPs was detected by using anti-γ-H2A.X immunofluorescence staining.The expression of genes in the ATR/Chk1/p53 signaling pathway was detected by real-time fluorescent quantitative polymerase chain reaction(qPCR),Western blotting,Tyramide signal amplification(TSA)multiplex immunofluorescence staining,and immunofluorescence co-localization,respectively.The ATR-specific inhibitor Ceralasertib(AZD6738)was administrated to MLE-12 cells in combination with PS-NPs to evaluate the recovery effect on cell proliferation and apoptosis.Results·Flow cytometry revealed that exposure to PS-NPs increased the total number of inflammatory cells and the number of each type of inflammatory cells in the BALF of mice with severe asthma,with a predominance of neutrophils.H-E and PAS staining showed significant increase in airway inflammatory cell infiltration and mucus secretion,as well as disruption of alveolar structure.In vitro,the CCK-8 assay demonstrated significant,dose-dependent inhibition of MLE-12 cell proliferation by PS-NPs.The Annexin V/PI double staining assay indicated a higher apoptosis rate of(56.20±3.84)%in PS-NP-exposed cells compared to(23.22±2.52)%in the control group.Immunofluorescence staining demonstrated that PS-NPs were phagocytosed by MLE-12 cells and localized around the nucleus.TUNEL staining confirmed enhanced apoptosis in AT2 cells in vivo.The immunofluorescence assay revealed that compared to the control group,the expression of the DNA damage marker γ-H2A.X increased in the experimental group.qPCR,Western blotting,and TSA multiplex staining results showed that PS-NP-induced elevated expression of mRNA and proteins was related to the ATR/Chk1/p53 pathway in MLE-12 cells.Moreover,immunofluorescence co-localization also confirmed the induction of ATR and p53 proteins in AT2 cells in vivo.The ATR-specific inhibitor Ceralasertib partially restored the PS-NP-induced inhibition of cell proliferation and enhancement of apoptosis in MLE-12 cells.Conclusion·NPs exposure leads to DNA damage in AT2 cells,activating the ATR/Chk1/p53 signaling pathway and exacerbating airway inflammation and alveolar damage in mice with severe asthma.

Objective:To investigate the effect and mechanism of miR-217 targeted regulation of extracellular signal-regulated kinase 2(ERK2)expression on activity and immune escape of non-small cell lung cancer cells(NSCLC).Methods:qRT-PCR was used to detect expression levels of miR-217 and ERK2 mRNA in NSCLC tissues,adjacent tissues,and HLF-1,A549 and HCC827 cell lines.Analyzed prognosis and survival status of NSCLC patients with different miR-217 expression level.Bioinformatics and dual luciferase gene reporting experiments were used to analyze the targeting relationship between miR-217 and ERK2.Cultivated NSCLC A549 cells and divided them into NC group,miR-217 inhibitor group,miR-217 mimic group,miR-217 mimic+ERK2 NC group and miR-217 mimic+ERK2 group.Except for the NC group without any treatment,all other groups were transfected with corresponding plasmids to analyze the proliferation activity and immune escape status of A549 cells in each group,and clarified the mechanism of action.Results:Compared with adjacent tissues,expression of miR-217 in NSCLC tissue was decreased,while expression of ERK2 mRNA was increased(P<0.05).Compared with human normal lung fibroblast HLF-1 cell lines,expression of miR-217 in NSCLC cell lines A549 and HCC827 were decreased,while expression of ERK2 mRNA was increased(P<0.05).Analysis of the relationship be-tween miR-217 and prognosis of NSCLC patients based on Kaplan-Meier Plotter database showed that low expression of miR-217 was associated with poor prognosis of patients(HR=0.90,P=0.033).Dual fluorescein reporter genes showed matching sequences between the 3'UTR regions of miR-217 and ERK2.miR-217 mimic fragment could inhibit ERK2-WT signal,but had no effect on ERK2-MUT.Compared with NC group,cell proliferation activity,PD-L1 and PD-L2 mRNA expression levels of miR-217 inhibitor group were in-creased,while CD8+T cell activity was decreased,and cell proliferation activity,PD-L1 and PD-L2 mRNA expression levels of miR-217 mimic group were decreased,while CD8+T cell activity was increased(P<0.05).Compared with miR-217 mimic group,cell pro-liferation activity,CD8+T cell activity,PD-L1 and PD-L2 mRNA expression levels of miR-217 mimic+ERK2 NC group had no signifi-cant changes(P>0.05),cell proliferation activity,PD-L1 and PD-L2 mRNA expression levels of miR-217 mimic+ERK2 group were increased,while CD8+T cell activity was decreased(P<0.05).Conclusion:Overexpression of miR-217 can reduce the activity of NSCLC cell A549,inhibit the expression of PD-L1,activate CD8+T cells in tumor microenvironment,and then inhibit immune es-cape,which may play a role by targeting ERK2.

Objective To investigate the correlation between the expression of long non-coding ribonucleic acid growth arrest specific 5(lncRNA GAS5),phospholysine phosphohistidine inorganic pyrophosphate phos-phatase(LHPP)and epithelial-mesenchymal transition(EMT)in cancer tissues of patients with non-small cell lung cancer(NSCLC)and its clinical significance.Methods Cancer tissues and adjacent tissues of 90 patients with NSCLC who underwent surgical resection in the First Hospital Affiliated to Hebei North College from June 2018 to January 2020 were collected.The expressions of lncRNA GAS5,LHPP and EMT-associated pro-teins[E-calmodulin(E-Cad),N-calmodulin(N-Cad),and vimentin(VIM)]were detected by real-time fluores-cence quantitative polymerase chain reaction.The relationship between lncRNA GAS5 and LHPP mRNA and clinicopathological features in cancer tissues of NSCLC patients was analyzed,and the correlation between ln-cRNA GAS5 and LHPP mRNA and EMT-associated proteins expression in cancer tissues of NSCLC patients was analyzed by Pearson correlation.Kaplan-Meier method was used to plot the survival curves of NSCLC pa-tients with different lncRNA GAS5 and LHPP mRNA expressions,and multivariate Cox regression was used to analyze the prognostic factors of NSCLC patients.Results The expressions of lncRNA GAS5,LHPP mR-NA and E-Cad mRNA in cancer tissues of NSCLC patients were lower than those in adjacent tissues,while the expressions of N-Cad mRNA and VIM mRNA were higher than those in adjacent tissues,with statistical sig-nificance(P＜0.05).Pearson correlation analysis showed that lncRNA GAS5 in cancer tissues of NSCLC pa-tients was positively correlated with E-Cad mRNA expression(r=0.724,P＜0.001),and negatively correla-ted with N-Cad mRNA and VIM mRNA expression(r=-0.699,-0.689).P＜0.001);lncRNA GAS5 was positively correlated with LHPP mRNA expression(r=0.651,P＜0.001).The mRNA expressions of ln-cRNA GAS5 and LHPP in cancer tissues of NSCLC patients with different degrees of differentiation,tumor TNM stage and lymph node metastasis were significantly different(P＜0.05).Kaplan-Meier survival curve a-nalysis showed that the 3-year overall survival rate in the lncRNA GAS5 high expression group[68.18％(30/44)]was higher than that in the lncRNA GAS5 low expression group[36.96％(17/46)].The 3-year overall survival rate in the high LHPP mRNA expression group[67.39％(31/46)]was higher than that in the lowLHPP mRNA expression group[36.36％(16/44)],and the difference was statistically significant(x2=10.274,10.322,P＜0.05).Low differentiation,TNM stage Ⅲ and lymph node metastasis were independent risk factors for death in NSCLC patients,and lncRNA GAS5≥1.32 and LHPP mRNA≥1.12 were independ-ent protective factors(P＜0.05).Conclusion The low expression of lncRNA GAS5 and LHPP mRNA in cancer tissues of patients with NSCLC is related to EMT-associated proteins expression,differentiation de-gree,tumor TNM stage,lymph node metastasis and prognosis,and may become a new target for the diagnosis and treatment of NSCLC.

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.

OBJECTIVE To prepare Gambogic acid （GA） nanocapsules （GA-LNCs） and Neogambogic acid （NGA） nanocapsules（NGA-LNCs），and to evaluate their antidiabetic activities. METHODS Using water as the aqueous phase ，medium- chain triglyceride as the oil phase and polyethylene glycol monostearate as the surfactant ，GA-LNCs and NGA-LNCs were prepared by phase inversion method. Using entrapment efficiency and drug-loading amount as index ，the formulation technologies of above 2 nanocapsules were optimized by simplex lattice design. Its physical and chemical properties were investigated. The diabetic mice model was established. GA-LNCs and NGA-LNCs （1.92 and 2.42 mg/kg respectively ）were given intragastrically ，once a day ，for consecutive 6 weeks. The fasting blood glucose of mice ，the activities of superoxide dismutase （SOD）and glutathione peroxidase （GSH-Px），the contents of malondialdehyde （MDA），total cholesterol （TC），triglyceride （TG），high-density lipoprotein cholesterol（HDL-C）and low-density lipoprotein cholesterol （LDL-C）were all detected. RESULTS The optimal formulation of 2 kinds of nanocapsules included 60％ water，10％ medium-chain triglyceride ，30％ polyethylene glycol monostearate （total amount of the three was 2 g）and 35 mg GA or NGA . The encapsulation efficiencies of GA-LNCs and NGA-LNC obtained by the optimal formulation were （92.01±0.68）％ and（93.12±2.11）％；the drug-loading amount were （0.99±0.21）％ and（1.21±0.22）％， respectively. GA-LNCs and NGA-LNCs were yellow ，homogeneous and transparent liquid without precipitation. They were spherical in microscopic shape ， and had obvious shell- Δ 基金项目：吉林省科技发展计划项目（No.20200404090YY）；吉 membrane structure. The particle sizes were （28.11 ± 9.76） 林省教育厅科学技术研究项目（No.JJKH20210372KJ） ＊硕士研究生 。研究方向 ：植物药 。E-mail：zhanhe0108@163. and（22.06±6.84）nm；Zeta potential were （－4.09±1.00） com and（－17.40±1.32）mV，and polydispersity were 0.93±0.06 # 通信作者：讲师，博士。研究方向：中药有效成分治疗疾病的作 and 0.74±0.12. The results of animal experiments showed that 用机制。E-mail：chenweijia_jlau@163.com both GA-LNCs and NGA-LNCs could sig nificantly increase 中国药房 2022年第33卷第9期 China Pharmacy 2022Vol. 33 No. 9 ·1075· the activities of SOD and GSH-Px and the seru m content of HDL-C （P＜0.05 or P＜0.01）in model mice ，and significantly decreased the fasting blood glucose and the serum contents of MDA ， TC， TG and LDL-C （P＜0.05 or P＜0.01）. CONCLUSIONS GA-LNCs，NGA-LNCs prepared in this study are good in physical and chemical properties and have good anti-diabetes activity.

Objective: To investigate the incremental value of coronary flow reserve (CFR) assessed by cadmium zinc telluride(CZT)-SPECT as an adjunct to myocardial perfusion imaging (MPI) in the diagnosis of coronary artery disease (CAD). Methods: Data of 132 patients (89 males, 43 females; 40-81 years) with or suspected with CAD who successfully underwent rest and stress MPI and CFR from November 2017 to October 2018 in Zhongshan Hospital Affiliated to Fudan University were retrospectively analyzed. Based on coronary angiography (CAG) as the " gold standard" , the value of MPI and MPI+ CFR in the diagnosis of CAD was evaluated and compared. χ² test or Fisher exact probability test was used for data analysis. Results: Of 132 patients, 61 (46.2%) were CAD with stenosis of at least 75% in one vessel (47.5%, 29/61), two vessels (34.4%, 21/61), or three vessels (18.0%, 11/61). A total of 104 (26.3%) vessels with stenosis of at least 75%, 25 (6.3%) vessels with stenosis of 65%-74%, and 30 (7.6%) vessels with stenosis of 50%-64% were found in 396 vessels. For detecting coronary stenosis of at least 75%, the sensitivity and accuracy of MPI on per-patient analysis were 86.89%(53/61) and 68.94%(91/132), which increased to 96.72%(59/61; χ²=3.921, P<0.05) and 87.88%(116/132; χ²=13.984, P<0.01) by MPI+ CFR. On per-vessel analysis, the sensitivity and accuracy of MPI were 72.12%(75/104) and 77.53%(307/396) and increased to 96.15%(100/104; χ²=22.511, P<0.01) and 85.10%(337/396; χ²=7.479, P<0.05) by MPI+ CFR. The sensitivity of MPI for predicting one, two, and three vessels disease were 72.41%(21/29), 42.86%(9/21), and 5/11 and were improved to 93.10%(27/29; χ²=4.350, P=0.037), 90.48%(19/21; χ²=10.714, P=0.001), and 11/11 (P=0.012) by MPI+ CFR. For coronary with stenosis of 65%-74%, the sensitivity of MPI was 24.00%(6/25) and was improved to 64.00%(16/25; χ²=8.117, P=0.004) by MPI+ CFR. For coronary with stenosis of 50%-64%, the sensitivity of MPI was 40.00%(12/30) and was improved to 76.67%(23/30; χ²=8.297, P=0.004) by MPI+ CFR. Conclusion As an adjunct to MPI, CFR can significantly improve the sensitivity and accuracy in the diagnosis of CAD, particularly for patients with mild stenosis and multivessel CAD.

Autophagy is a pathway of intracellular degradation, in which autophagic vacuoles are formed to transport intracellular biomacromolecules and damaged organelles to lysosomes. Autophagy plays an important role in the maintenance of the dynamic balance of liver function. Abnormal liver cells can be eliminated by autophagy. This article reviews the close relationship of autophagy with the proliferation of liver cells, non-parenchymal liver cells, and hepatic stem cells. Analysis has shown that autophagy may restore the volume and function of the liver by promoting the proliferation of liver cells and hepatic stem cells, which can be stopped in time to prevent tumor development. Autophagy may promote the activation of non-parenchymal liver cells during liver dysfunction, which can inhibit the regeneration of liver cells, and, in the meantime, lead to the development and progression of liver fibrosis. When the tumor is being formed, autophagy plays an important role in the transformation of normal cells into cancer cells; malignant regeneration of liver cells is activated but not terminated in time.

Objective To investigate the protective effect of augmenter of liver regeneration (ALR) against acute liver injury and related mechanisms.Methods HL-7702 cells were divided into normal control group,carbon tetrachloride (CCl4)-induced acute liver injury group,ALR+CCl4 intervention group,3-methyladerine (3-MA)+CCl4 intervention group,and ALR+3-MA+CCl4 intervention group.The ALR+CCl4 and ALR+3-MA+CCl4 intervention groups were transfected with ALR plasmids at 8 hours before CCl4 treatment.All groups except the normal control group were treated with CC14,and 30 minutes later,the 3-MA+CC14 and ALR+3-MA+CCl4 intervention groups were treated with 3-MA.The cells were collected at 24 hours after CCl4 treatment.The HL-7702 cells and supematant were collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (IU/L).Westem blot was used to measure the levels ofALR,cyclin D,cyclin E,proliferating cell nuclear antigen (PCNA),autophagy-related gene 7 (Atg7),and autophagy genes LC3,p62,and Beclin-1.Quantitative real-time PCR was used to measure the mRNA expression ofALR.A oneway analysis of variance was used for comparison of means between any two groups.Results The ALR+CCl4 intervention group had significant increases in the protein and mRNA expression of ALR compared with the acute liver injury group (both P ＜ 0.05).The CC14-induced acute liver injury group had significant increases in the protein and mRNA expression of ALR compared with the normal control group (both P ＜ 0.05).Compared with the CCl4-induced acute liver injury group,the ALR+CCl4 intervention group had significant reductions in ALT (0.73±0.17 IU/L vs 1.43±0.38 IU/L,P ＜ 0.05) and AST (19.85±1.83 IU/L vs 56.73±6.25 IU/L,P ＜ 0.05) in supematant,significantly increased expression of cyclin D,cyclin E,PCNA,LC3,Atg7,and Beclin-1 in hepatocytes,and significantly reduced expression of p62,which suggested that ALR protected the liver against acute liver injury,promoted the regeneration of hepatocytes,and enhanced the autophagy of hepatocytes.The ALR+3-MA+CCl4 intervention group had a significant reduction in the expression of regeneration-associated proteins compared with the ALR+CCl4 intervention group,while there was no significant difference between the ALR+3-MA+CCL4 intervention group and 3-MA+CCL4 intervention group,which suggested that after the inhibition of autophagy,there were significant reductions in the regeneration of hepatocytes and liver regeneration promoted by ALR.Conclusion ALR can promote the regeneration of hepatocytes in liver parenchyma,which is achieved by the regulation of autophagy.