Diabetic retinopathy (DR) is one of common causes of vision loss.Recent years,progress has been made on the signal pathway in DR which provides more theoretical basis for clinical therapies and more chance for developing targeted therapeutic drugs.Understanding the biological function of the signal pathway in DR is helpful for physicians to selectively control its biological activities,make medical decisions and optimize new approaches to the treatment of DR.How to closely combine the study of signal pathway and targeted therapy in practice is a key link of improving the therapeutic effect of DR.Therefore,we should pay attention to translational medicine and reinforce targeted therapy in DR.

Objective To evaluate the effects of lung-protective ventilation on the cerebral oxygen metabolism and postoperative cognitive function in elderly patients requiring one-lung ventilation (OLV).Methods Sixty patients of both sexes,aged 65-80 yr,weighing 45-75 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective radical resection for esophageal cancer performed via video-assisted thoracoscope with general aneshesia,were divided into 2 groups (n =30 each)using a random number table:volume-controlled ventilation group (group VCV) and protective ventilation group (group PV).In group VCV,the tidal volume (VT) was set at 10 ml/kg during two-lung ventilation (TLV) and at 7 ml/kg during OLV.In group PV,the VT was set at 7 ml/kg during TLV and at 5 ml/kg during OLV with positive end-expiratory pressure of 5 cmH2O,and lung recruitment maneuver was performed every 45 min with inspiratory pressure at 15,20 and 25 cmH2O,PEEP 5 cmH2O,3 breaths per pressure,5 s/breath.Before induction of anesthesia (T1),at 10 min of TLV (T2),at 30 min of OLV (T3) and at 15 min after restoration of TLV (T4),blood samples were taken from the radial artery and jugular bulb for blood gas analysis,and pH value,arterial oxygen partial pressure (PaO2),arterial carbon dioxide partial pressure (PaCO2),arterial oxygen saturation (SaO2) and jugular venous oxygen saturation (SjvO2) were recorded.Oxygenation index (OI),intrapulmonary shunt (Qs/Qt),arteriovenous blood O2 content difference (Da-jvO2) and cerebral O2 extraction rate (CERO2) were calculated at the same time.Cognitive function was assessed using Mini-Mental State Examination at 7 days and 1 month after operation,and the development of postoperative cognitive dysfunction was recorded.Results PaO2,DajvO2,CERO2 and Qs/Qt were significantly higher and SjvO2 and OI were lower at T2-4 than at T1 in two groups (P＜0.05).PaO2,SjvO2 and OI were significantly lower and Qs/Qt and CERO2 were higher at T3 than at T2,and Da-jvO2 was higher at T3-4 than at T2 in two groups (P＜0.05).Compared with group VCV,PaO2,PaCO2,SjvO2 and OI were significantly increased and Qs/Qt,Da-jvO2 and CERO2 were decreased at T3,the Mini-Mental State Examination scores were increased on postoperative day 7,and the incidence of postoperative cognitive dysfunction was decreased in group PV (P＜O.05).Conclusion Lungprotective ventilation is helpful in improving postoperative brain function of elderly patients requiring OLV.

Objective To evaluate the effect of lung protective ventilation strategy on inflammatory responses in brain tissues of elderly patients requiring one-lung ventilation (OLV) during radical resection for esophagus cancer.Methods Sixty patients of both sexes,aged 65-80 yr,weighing 45-75 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective radical resection for esophageal cancer,were divided into volume-controlled ventilation (VCV) group (n =30) and VCV plus protective ventilation strategy group (PV group,n =30) using a random number table.In group VCV,the tidal volume was set at 10 ml/kg during two-lung ventilation (TLV) and at 7 ml/kg during OLV with inspiratory/expiratory ratio 1:2.In group PV,the tidal volume was set at 7 ml/kg during TLV and at 5 ml/kg during OLV with inspiratory/expiratory ratio 1:2 and positive end-expiratory pressure 5 cmH2O,and lung recruitment maneuver was performed every 45 min.End-tidal pressure of carbon dioxide was maintained at 35-45 mmHg,and bispectral index value at 40-60 in both groups.Before induction of anesthesia (T1),at 10 min of TLV (T2),at 30 min of OLV (T3),at 15 min after restoration of TLV (T4) and at 24 h after operation (T5),jugular bulb venous blood samples were taken for determination of serum glial fibrillary acid protein,tumor necrosis factor-α and interleukin-6 concentrations by enzyme-linked immunosorbent assay.The cognitive function was assessed using Mini-Mental State Examination before operation (T0),at T5 and at 3 and 7 days after operation (T6,7).The occurrence of postoperative delirium was recorded.Results Compared with group VCV,the serum concentrations of tumor necrosis factor-α,interleukin-6 and glial fibrillary acid protein were significantly decreased at T3-5,Mini-Mental State Examination scores were increased at T6,7,and the incidence of postoperative delirium was decreased in group PV (P＜0.05).Conclusion The mechanism by which lung protective ventilation strategy decreases the development of postoperative cerebral dysfunction is related to reduction of inflammatory responses in brain tissues of elderly patients requiring OLV during radical resection for esophagus cancer.

Objective To establish lentiviral expression vectors for Smurf1 silencing and assess the effects of Smurf1 silencing on cell migration.Methods HeLa and A549 cells were infected with lentiviral expression vectors for Smurf1 silencing respectively.After 7 days,the stable cell lines with Smurf1 silencing were obtained after puromycin-resistance screening,enrichment and expansion.The intracellular gene and protein levels of Smurf1 were detected by qPCR and western blot.Transwell assay was used to assess the effect of Smurf1 silencing on cell migration.Results The stable cell lines with Smurf1 silencing are constructed successfully.Silencing of Smurf1 down-regulated cell migration rate detected by Transwell assay.Conclusion Smurf1 promotes cell migration.

In order to investigate the species and categorization of Gasterophilus in Ili horse.We analysised the COI gene of the identified Gasterophilus dominant species and constructed NJ phylogenetic tree in the study.The results showed that infection rate was 100％ in total of 16 775 the third phase Gasterophilus instar larvae.Four Gasterophilus species were identified,and showed serious mix infections.Dominant species were Gasterophilus nasalis,its relative dominance were 53.17％,and prefer to live in the cardia,others to irregular live in the pylorus of the horses.COI gene homology of GasterophiIus nasalis,Gasterophilus intestinalis,Gasterophilus pecorum,Gasterophilus haemorrhoidalis (GenBank Accession No.:GU265752.1,KR230402.1,KU578262.1,KT946620.1) were 99％,99％,99％ and 100％ respectively.Phylogenetic analysis results showed that the data were clustered with the Gasterophilus app.which publshed on the GenBank.G.intestinalis and G.haemorrhoidalis cluster together first,and then cluster with G.nasalis,at last all three kinds of Gasterophilus cluster with G.pecorum.When the COI gene is the target,in-group and out-group of the Gasterophilus can forms an independent evolutionary branch.This study provides useful parameters for the classification of Gasterophilus.

In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.

Macrophages are innate immune cells connected with the development of inflammation. Retinoic acid has previously been proved to have anti-inflammatory and anti-arthritic properties. However, the exact mechanism through which retinoic acid modulates arthritis remains unclear. This study aimed to investigate whether retinoic acid ameliorates rheumatoid arthritis by modulating macrophage polarization. This study used retinoic acid to treat mice with adjuvant arthritis and evaluated anti-inflammatory effects by arthritis score, thermal nociceptive sensitization test, histopathologic examination and immunofluorescence assays. In addition, its specific anti-arthritic mechanism was investigated by flow cytometry, cell transfection and inflammatory signaling pathway assays in RAW264.7 macrophages in vitro. Retinoic acid significantly relieved joint pain and attenuated inflammatory cell infiltration in mice. Furthermore, this treatment modulated peritoneal macrophage polarization, increased levels of arginase 1, as well as decreased inducible nitric oxide synthase expression. In vitro, we verified that retinoic acid promotes macrophage transition from the M1 to M2 type by upregulating mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression and inhibiting P38, JNK and ERK phosphorylation in lipopolysaccharide-stimulated RAW264.7 cells. Notably, the therapeutic effects of retinoic acid were inhibited by MKP-1 knockdown. Retinoic acid exerts a significant therapeutic effect on adjuvant arthritis in mice by regulating macrophage polarization through the MKP-1/MAPK pathway, and play an important role in the treatment of rheumatic diseases.