ObjectiveTo investigate the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） in mice by Data-Independent Acquisition （DIA） proteomics. MethodsThe α-Synuclein （α-Syn） transgenic PD mice were selected as suitable models for PD， and they were randomly assigned into PD， ASH （61.25 mg·kg^-1）， and Madopar （97.5 mg·kg^-1） groups. Male C57BL/6 mice of the same age were selected as the control group， with eight mice in each group. Mice were administrated with corresponding drugs by gavage once a day for 20 days. The pole climbing time and the number of autonomic activities were recorded to evaluate the exercise ability of mice. Hematoxylin-eosin staining was employed to observe neuronal changes in the substantia nigra of PD mice. Immunohistochemistry （IHC） was employed to measure the tyrosine hydroxylase （TH） activity in the substantia nigra and assess the areal density of α-Syn in the striatum. DIA proteomics was used to compare protein expression in the substantia nigra between groups. IHC was utilized to validate key differentially expressed proteins， including Lactotransferrin， Notch2， Ndrg2， and TMEM 166. The cell counting kit-8 （CCK-8） method was used to investigate the effect of ASH on the viability of PD cells with overexpression of α-Syn. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the protein and mRNA levels of Lactotransferrin， Notch2， Ndrg2， and TMEM 166 in PD cells. ResultsCompared with the control group， the model group showed prolonged pole climbing time， diminished coordination ability， reduced autonomic activities （P<0.01）， and reduced swelling neurons. Compared with the model group， ASH and Madopar reduced the climbing time， increased autonomic activities （P<0.01）， and ameliorated neuronal damage. Compared with the control group， the model group showed a decrease in TH activity in the substantia nigra and an increase in α-Syn accumulation in the striatum （P<0.01）. Compared with the model group， the ASH group showed an increase in TH activity and a reduction in α-Syn accumulation （P<0.05）. DIA proteomics revealed a total of 464 differentially expressed proteins in the model group compared with the control group， with 323 proteins being up-regulated and 141 down-regulated. A total of 262 differentially expressed proteins were screened in the ASH group compared with the model group， including 85 proteins being up-regulated and 177 down-regulated. Kyoto encylopedia of genes and genomes （KEGG） pathway analysis indicated that ASH primarily regulated the Notch signaling pathway. The model group showed up-regulation in protein levels of Notch2， Ndrg2， and TMEM 166 and down-regulation in the protein level of Lactotransferrin compared with the control group （P<0.01）. Compared with the model group， ASH down-regulated the protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.05） while up-regulating the protein level of Lactotransferrin （P<0.01）. The IHC results corroborated the proteomics findings. The cell experiment results showed that compared with the control group， the modeling up-regulated the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while down-regulating the mRNA and protein levels of Lactotransferrin （P<0.01）. Compared with the model group， ASH reduced the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while increasing the mRNA and protein levels of Lactotransferrin （P<0.05， P<0.01）. ConclusionASH may Synergistically inhibit the Notch signaling pathway and mitigate neuronal damage by down-regulating the expression of Notch2 and Ndrg2. Additionally， by up-regulating the expression of Lactotransferrin and down-regulating the expression of TMEM166， ASH can address brain iron accumulation， intervene in ferroptosis， inhibit mitophagy， and mitigate reactive oxygen species damage， thereby protecting nerve cells and contributing to the treatment of PD.

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective To investigate the knee disorders and risk factors in electromechanical soldiers of a warship,so as to provide a basis for prevention and treatment measures.Methods The knee disorders and treatment data of 200 electromechanical soldiers(study group)and 200 soldiers from other departments(control group)were colected by questionnaire survey and medical records.Results The incidence of knee diseases was 37.5%(75 cases)in the study group,which was significantly higher than that in the control group(16.0%,32 cases,P＜0.05).Traumatic and degenerative diseases were the main types of knee disorders.Age and body mass index were the influencing factors of knee disorders in electromechanical soldiers.Conclusion There is a high incidence of knee disorders in electromechanical soldiers,which is related to a variety of factors.Appropriate prevention and treatment measures are of great significance to reduce the incidence of knee disorders,promote rapid recovery,and reduce non-combat casualty.

Infectious pneumonia caused by bacteria,viruses,or other pathogenic microorganisms remains a huge threat to human health.Immunocyte-derived biomimetic nano-drug delivery systems can be used for drug delivery by taking advantage of the natural anti-inflammatory effect of immune cells and thus show great potential in lung-targeted therapy.This review begins by introducing different types of immune cells in the lung.The preparation methods of immunocyte-derived biomimetic nano-drug delivery systems and their applications in bacterial pneumonia,viral pneumonia,acute respiratory distress syndrome and cytokine storms are also reviewed.The review is expected to provide data for the targeted therapy of infectious pneumonia.

Objective:To analyze and evaluate the safety and efficacy of a Chinese domestically manufactured Heart Con-type implantable third-generation magnetic and hydrodynamic levitation left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), by reporting the results of eleven-center clinical trial on 50 cases.Methods:This study was a multicenter clinical trial, designed by means of prospective, multicenter and single-group target value. 50 subjects with ESHF were competitively enrolled and treated with HeartCon as the LVAD in eleven centers. The primary efficacy measure was survival, defined as either the subjects experiencing the transition to heart transplantation(HT) or myocardial recovery assisted by the device within 90 days, or as successfully assisted by the LVAD for full 90 days after implantation. The target survival rate was 60%, other observations included implantation success rate, mortality, pump failure needing replacement or emergency heart transplantation.Results:All enrolled 50 patients received LVAD implantation successfully, 46 survived with the pump for 90 days, 1 patient transitioned to heart transplantation, and 3 patients experienced pump thrombosis, within which 2 patients underwent pump replacement and continued to live with the pump for 90 days, and the other one received emergency heart transplantation. There were no dropout subjects. The survival rate at full 90 days after HeartCon implantation was 100%. The survival rates with pump in the full set analysis and the protocol set analysis were 96.00% and 95.92% respectively, which were higher than the target value of 60%. The differences were both statistically significant( P<0.05). Conclusion:The results of the multicenter clinical trial with the largest sample size in China using domestically manufactured third-generation LVAD has demonstrated that, HeartCon is a safe and effective LVAD to treat ESHF patients.

Objective To observe the effect of out-hospital standardized treatment on the recurrence of the first onset of acute unprovoked pulmonary thromboembolism (PE) after discontinued anticoagulant therapy or during anticoagulation therapy in PE patients after treatment and discharged from hospital.Methods A prospective study of patients with acute PE admitted into emergency ICU for training in out-hospital standardized anticoagulation treatment was carried out from January 2015 to December 2016 (observation group).Another cohort of EP patients without training in out-hospital standardized anticoagulation treatment admitted from January 2010 to December 2014 was enrolled for retrospective analysis(control group).The out-hospital standardized anticoagulation treatment strategy included the guidance of anticoagulation therapy,record all of the patients' symptoms related with recurrent EP both during and discontinuous anticoagulant treatment,V/O scan at 3 months,6 months and 12 months follow-up,respectively.The patients with ceased anticoagulant therapy would be followed up for at least one year.Patients with signs of recurrence would have a definite diagnosis at once.The anticoagulation status and outcome of the patients in control group found in out-patient department were recorded.Results ① There were 129 patients with acute unprovoked PE in observation group and 246 in control grouThere were no significance difference both in mean age and gender between two groups (P ＜0.05).② Recurrence rate was 11.63％ in observation group and 22.36％ in control group (P ＜0.01);③ There was significance difference in mortality rate between observation group (3.1％) and control group (10.85％) (P ＜0.05).There was also significant difference in rate of missing follow-up between observation group (10.85％) and control group (21.54％) (P＜0.001),and.there was significant difference in rate of discontinuous anticoagulation therapy between observation group (1.55％) and control group (8.5％) (P ＜0.01).④ There was no significance difference seen in the rate of patients exposed to multiple risk factors of arteriosclerosis between observation group (82.25％) and control group (77.64％) (P＜0.05).But the target rate of controlling various risk factors of arteriosclerosis was 79.31％ in observation group and 54.97％ in control group respectively (P＜0.05).Conclusions Standardized treatment can effectively reduce the recurrent rate of the venous episodes of the patients with first episode of acute unprovoked pulmonary thromboembolism;Recurrent venous episodes of the PE patients who exposed to the multiple risk factors of arteriosclerosis require more attentions.

Purpose To prepare superparamagnetic iron oxide nanoparticles (SPION) probe targeted and modified by MUC1 murin (MUC1) in order to explore its MRI characteristics in pancreatic cancer transplantation model.Materials and Methods Chemical conjugate method was adopted for coupled response of MUC1 and SPION to construct targeted probe and tested its basic physical properties,including water and diameter,surface charge and MR signal measuring.Meanwhile,nude mice model of pancreatic cancer transplant subcutaneous sarcoma was set up to study imaging effect inside the nude mice.Transplant sarcoma specimen was taken and immunohistochemical and Western blot were adopted to measure MUC1 expression.Results Partial size of the prepared particle probe was approximately 63.5 nm and surface charge was about 10.2 mV.The probe solution could obviously decrease MR transverse relaxation time (T2 value).In vitro experiment,MUC 1 could selectively gather on nude mice transplant sarcoma model could greatly lower T2 signal intensity.Conclusion Prepared probe has small partial size,superparamagnetic and other advantages.It can realize combination with pancreatic cancer tissue specificity and provide reliable in vivo iconology in early stage for disease diagnosis through vitro imaging.

Objective To investigate the effect of the timing of endoscopic retrograde cholangiopancreatography(ERCP)treat-ment option on the respiratory burst and inflammatory factor level for acute obstructive suppurative cholangitis(AOSC)patients. Methods A total of 98 patients with AOSC who were treated in our hospital from January 2013 to June 2016 were retrospectively analyzed.The patients were divided into A group and B group according to the time of ERCP operation.42 cases in A group were received ERCP within 6 h after admission.56 cases in B group were received ERCP in 6-24 h after admission.,The serum levels of inflammatory cytokines were compared between the two groups before and after treatment.The apoptosis rate and respiratory burst rate of peripheral hematoma were compared between the two groups before and after treatment.The complications and death rate of the patients in the two groups were recorded.Results After treatment,the levels of TNF-α and IL-6 in the A group were signifi-cantly lower than those in the B group and the IL-10 level was significantly higher in the B group(P<0.05).After treatment,the rate of neutrophil apoptosis in the A group was significantly higher than that in the B group(P<0.05),and the respiratory burst level in the A group was significantly lower than that in the B group(P<0.05).The incidence number of complications and death in patients in group A was significantly lower than that in group B(P< 0.05).Conclusion ERCP treatment for patients with AOSC should be performed as early as possible and as soon as possible.Early ERCP treatment is safe and effective and can alleviate the inflammatory reaction of patients,improve the survival rate of patients,and is worthy of clinical promotion.

Objective To understand the drug resistance and changes of Pseudomonas aeruginosa in Tianjin Medical University Eye Hospita and to explore the relationship between the drug resistance and the dosage of antimicrobial agents, so as to provide the basis for clinical rational drug use.MethodsUsage of antibiotics in our hospital during 2012 to 2016 were analyzed retrospectively, and the drug resistance of pseudomonas aeruginosa were calculated respectively.SPSS 22.0 software was used to analyze the drug resistance and the frequency of use of antimicrobial agents (DDDs).ResultsResistance rate of pseudomonas aeruginosa to aztreonam, ceftazidime and meropenem were decreased gradually.Resistance rate of pseudomonas aeruginosa to gentamicin increased gradually.The resistance of pseudomonas aeruginosa to piperacillin, imipenem, cefepime, evil ciprofloxacin, piperacillin/tazobactam tazobactam and cefempidone/sulbactam is in a state of fluctuation.Piperacillin DDDs were significantly negatively correlated with gentamicin resistance.There was a significant positive correlation between imipenem DDDs and gentamicin resistance and there was a significant negative correlation between imipenem DDDs and drug resistance rates of piperacillin, imipenem, ceftazidime, meropenem, levofloxacin and cefoperazone/sulbactam.There was a significant positive correlation between aztreonam DDDs and ceftazidime, meropenem, ciprofloxacin and cefoperazone/sulbactam, There was a significant negative correlation between cephalosporin DDDs and gentamicin resistance rates.There was a significant positive correlation between the DDDs of piperacillin/tazobactam and the resistance rate of piperacillin/tazobactam;the resistance rates of cefoperazone/sulbactam DDDs to aztreonam and meropenem were Significant negative correlation.ConclusionDrug resistance of pseudomonas aeruginosa and the dosage of clinical antibacterial drug is closely related, suggesting that clinicians should use antibiotics for clinical rationally, in order to reduce the number of drug resistance of pseudomonas aeruginosa.