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 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.

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.

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.

Objective To evaluate the lung-protective effect of lung-protective ventilation (LPV) combined with ventilatory mode pressure-controlled ventilation-volume guaranteed (PCV-VG) in elderly patients undergoing one-lung ventilation (OLV).Methods Eighty American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients,aged 65-80 yr,with body mass index of 15-28 kg/m2,scheduled for elective radical resection for esophageal cancer performed via video-assisted thoracoscope,were divided into 4 groups (n=20 each) using a random number table:control group (group C),PCV-VG group,LPV group and LPV combined with PCV-VG group (group LPV+PCV-VG).At 20 min after changing the body position during two-lung ventilation (T1),30 min of OLV (T2) and 20 min after restoration of two-lung ventilation (T3),blood samples were collected from the radial artery for blood gas analysis and for determination of peak airway pressure (Ppeak),mean airway pressure (P) and dynamic lung compliance (Cdyn).Alveolar-arterial oxygen gradient,intrapulmonary shunt (Qs/Qt),dead space fraction (Vd/VT) and respiratory index were calculated at T2.Blood samples were collected from the radial artery before induction of anesthesia and at the end of operation for determination of plasma neutrophil elastase (NE) concentrations by enzyme-linked immunosorbent assay.The Clinical Pulmonary Infection Score (CPIS) was assessed at 1 and 7 days after operation,and the development of pulmonary complications such as respiratory failure,pulmonary atelectasis and pulmonary infection was recorded within 7 days after operation.Results Compared with group C,Ppeak was significantly decreased,and P was increased in group PCV-VG,Ppeak and PaCO2 were significantly increased and pH value,Vd/VT and Qs/Qt were decreased in group LPV,Ppeak,Vd/VT,Qs/Qt,pH value and postoperative CPIS were significantly decreased,and P Cdyn and PaO2 were increased in group LPV+PCV-VG,and the NE concentration at the end of operation was significantly decreased in PCV-VG,LPV and LPV+PCV-VG groups (P＜0.05).Compared with group PCV-VG,P Cdyn and PaO2 were significantly increased,and pH value,Qs/Qt,NE concentration at the end of operation and CPIS were decreased in group LPV+PCV-VG (P＜0.05).Compared with group LPV,Ppeak,Qs/Qt,NE concentration at the end of operation and CPIS were significantly decreased,and Cdyn was increased in group LPV+PCV-VG (P＜0.05).Pulmonary complications such as respiratory failure,pulmonary atelectasis and pulmonary infection were not observed after operation in the four groups.Conclusion LPV combined with PCV-VG can optimize the lung-protective effect in elderly patients undergoing OLV.

The aim of the study was to develop a simple, rapid and accurate LC-MS/MS method for the determination of digoxin.Digoxin-d3 was taken as the internal standard (IS), and sample preparation was achieved by liquid-liquid extraction.Chromatographic separation was performed on a Kinetex C18 column (2.1 mm × 50 mm, 2.6 μm; Phenomenex) using an isocratic elution with merely 2 min for each sample.The mobile phase consisted of water and acetonitrile solutions, both containing 1 mmol/L ammonium acetate and 1 mmol/L formic acid (55∶45).The detection was conducted on a TripleQuadTM 4500MD mass spectrometer coupled with electrospray ionization interface under positive-ion multiple reaction monitoring mode.The transitions were m/z 798.5 → 651.3 and m/z 801.6 → 654.4 for digoxin and digoxin-d3, respectively.Results showed that the method was linear over the range of 0.100-20.0 ng/mL.The selectivity, accuracy and precision, recovery and stability of the method were all within the acceptable limits with no matrix effect.This method was successfully applied to a girl treated with digoxin with substantial improvement of therapeutic effect and elimination of toxic reaction, so it can provide valuable fuidance and reference for individualized medication in clinical practice.

Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.

Objective To construct an evidence-based prevention and management programme for peristomal moisture-associated skin damage in patients with enterostomy,and to evaluate its clinical effectiveness in improving the knowledge level of nurses and patients about peristomal moisture-associated skin damage in patients with enterostomy and reducing the incidence and severity of peristomal moisture-associated skin damage.Methods Through literature screening,evaluation,and summary,the best evidence for the prevention and management programme of peristomal moisture-associated skin damage in patients with enterostomy was summarized.From October 2021 to March 2022,based on the Ottawa research application model,review indicators were developed based on the best evidence for clinical review,identifying obstacles and promoting factors in evidence application,and developing action strategies to improve the evidence-based practice content for the prevention and management of peristomal moisture-associated skin damage in patients with enterostomy.From April to June 2022,evidence-based practice was conducted in the oncology surgery ward of a tertiary hospital in Anhui Province.The implementation rate of various review indicators by nurses,the knowledge level of peristomal moisture-associated skin damage of nurses and patients,and the incidence and severity of peristomal moisture-associated skin damage were compared before and after evidence-based practice.Results 46 cases were included before the evidence-based practice and 49 cases were included after the evidence-based practice.After evidence-based practice,the implementation rate of each review index was improved;the overall implementation rate increased from(0-66.67％)to(83.33％-100％);the score of the patient's knowledge questionnaire on peristomal moisture-associated skin damage was increased from(69.67±8.31)to(80.18±8.07).The score of the nurse's knowledge questionnaire on peristomal moisture-associated skin damage was increased from(79.83±5.97)to(88.28±5.43).At 4 weeks and 12 weeks of discharge,the incidence of peristomal moisture-associated skin damage was decreased,with a statistically significant difference(P＜0.05);the severity of peristomal moisture-associated skin damage was also significantly reduced,with a statistically significant difference(P＜0.05).Conclusion Conducting evidence-based practice for the prevention and management of peristomal moisture-associated skin damage can effectively improve the implementation rate of nurse review indicators,improve the knowledge level of nurses and patients with peristomal moisture-associated skin damage,and reduce the incidence and severity of peristomal moisture-associated skin damage in patients with enterostomy.