Objective To study the clinical value of portable echocardiography system in diagnosis for acute paroxysmal dyspnea.Methods Clinical data of 81 patients with acute paroxysmal dyspnea recorded by a portable echocardiography apparatus at their bedside were retrospectively analyzed,and compared to those of 45 patients by conventional echocardiography.Results The 2D images in portable echocardiograph were similar to those of conventional echocardiograph.Diagnosis could be established in 74 (91.4%),corrected in six (7.4%) and not confirmed only in one (1.2%) of 81 patients with acute paroxysmal dyspnea by portable echocardiography system.And,portable echocardiography system could be used to diagnose pericardial effusion and to monitor perieardial puncturing and draining at bedside. Conclusions Portable echocardiography systems can provide rapid,accurate and valuable information on diagnosis and treatment for acute paroxysmal dyspnea,and make its clinical intervention accurate,scientific and effective,bringing echocardiography performed at bedside possible.

OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.

Objective To evaluate the efficacy and safety of low-dose decitabine and homoharringtonine combined with CAG regimen (cytarabine, aclarubicin and recombinant human granulocyte colony-stimulating factor) (DHCAG regimen) in treatment of acute myeloid leukemia (AML). Methods Nineteen patients who were treated with DHCAG regimen in the 920th Hospital of Joint Logistics Support Force from July 2017 to June 2018 were retrospectively analyzed. Among them, 13 cases were newly diagnosed, 6 cases were ineffective or relapsed; 2 cases were elderly (≥60 years old); 15 cases had pulmonary infection before chemotherapy, and 4 cases had no lesions in the lungs when admitted to hospital. The remission rate and chemotherapy-related adverse reactions were analyzed. Results After 19 patients received one course of DHCAG regimen, 16 patients had complete remission, 1 patient had partial remission, 2 patients had no remission, and the overall response rate was 89.5% (17/19). Four patients with undetected lung disease before chemotherapy had no infection in the lungs after treatment. Among 15 patients with pulmonary infection before treatment, 1 patient died of pulmonary infection progress, the remaining 14 cases were grade 1-2 infection. 7 cases had bleeding, and 3 cases had nausea and vomiting, all of which were grade 1-2. Conclusion The remission rate of DHCAG regimen in treatment of AML is high, and its adverse reactions are tolerable.

Objective:To establish an in vivo diffusion model of Treponema pallidum (Tp) in New Zealand rabbits. Methods:A standard strain of Tp (Nichols strain) was recovered in the testes of New Zealand rabbits, and isolated and passaged continuously. The suspensions of the second-passage Tp were collected and inoculated onto the dorsal skin of New Zealand rabbits. After 21-day infection, the New Zealand rabbits were anesthetized and sacrificed, blood samples were collected, and skin tissues at the infection site as well as liver, spleen, testes and lymph nodes were aseptically resected. Real-time fluorescence-based quantitative PCR was performed to detect the spread of Tp in different tissues and organs.Results:On day 21 after infection with Tp, skin lesions such as indurations and ulcers were seen at all inoculated sites of New Zealand rabbits. Pathological examination showed a lot of inflammatory cells in the infected lesions, mainly including plasma cells, macrophages and lymphocytes. Real-time fluorescence-based quantitative PCR revealed a large number of Tp in tissues and organs, such as liver, spleen and testes.Conclusion:After inoculation with Tp in the dorsal skin of New Zealand rabbits, Tp could spread to the liver, spleen, testes and other tissues and organs through blood and lymph nodes, and the in vivo diffusion model of Tp strains in New Zealand rabbits was successfully constructed.

OBJECTIVENeonatal septicemia is a common and severe infection, which often results in death. Early diagnosis and treatment of neonatal septicemia may help decrease neonatal mortality. Recently, many studies sought to explore the possibility of early diagnosis of this disease. The high affinity Fcgamma-receptor I (CD(64)) was purposefully chosen as a potential marker for identifying neonatal septicemia. The present study was designed to evaluate neutrophil CD(64) level for early diagnosis of neonatal septicemia.

METHODSEighty-nine suspected neonatal septicemia cases were recruited into the study. Five non-specific indices, i.e., C-reactive protein (CRP), micro-erythrocyte sedimentation rate (mESR), white blood cell count, platelet count and the ratio of immature neutrophil count to total neutrophil count were measured for each patient. The patients were divided into septicemia group (n = 39) and non-septisemic infection group (n = 50) according to the diagnostic criteria for neonatal septicemia. Nineteen hospitalized neonates with non-infectious diseases were enrolled as controls (n = 19). The levels of peripheral blood neutrophil CD(64) were measured by using flow cytometry. The positive rate, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CD(64) were calculated.

RESULTSThe levels of peripheral blood neutrophil CD(64) in septicemia patients were (75.6 +/- 8.9)%, which were significantly higher than those of non-septisemic infection group (29.1 +/- 6.2)% and control group (5.1 +/- 1.1)% (P < 0.05), respectively. There were no significant differences in the levels of CD(64) expression between the patients with Gram-negative (79.5 +/- 3.5)% and Gram- positive (76.4 +/- 5.0)% (P > 0.05) bacterial infection. The levels of CD(64) of the cases with septicemia significantly decreased at day 10 of treatment with antibiotics. The detection of CD(64) (cutoff value > 30%) for suspected septicemia showed high sensitivity (97.4%), specificity (84.0%), PPV (82.6%), and NPV (97.6%). The positive rate of CD(64) detection (62.9%) was much higher than that of the blood culture test (19.1%) and that of the five nonspecific indices (29.2%, P < 0.05, respectively).

CONCLUSIONThe expression of CD(64) increased in neonatal septicemia cases. The measurement of cell surface expression of CD(64) on neutrophils may be helpful to early diagnosis, evaluation of severity of infection and observation of therapeutic effects for neonatal septicemia.

Biomarkers ; blood ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Early Diagnosis ; Female ; Flow Cytometry ; Humans ; Infant, Newborn ; Male ; Neutrophils ; immunology ; Platelet Count ; Predictive Value of Tests ; Receptors, IgG ; immunology ; Sensitivity and Specificity ; Sepsis ; blood ; diagnosis ; immunology ; Severity of Illness Index

Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.

Intracellular neurofibrillary tangles resulting from abnormal hyperphosphorylation of Tau protein constitute one of the principal pathological markers of Alzheimer′s disease. Existing studies have indicated that BSc3094 is an efficacious inhibitor of Tau protein aggregation, capable of binding to Tau protein, inhibiting Tau protein phosphorylation, and enhancing cell viability concurrently, holding significant potential in treating Alzheimer′s disease. Nevertheless, due to the presence of the blood-brain barrier, it is challenging for drugs to penetrate the brain and exert their effects, and whether BSc3094 can treat Alzheimer′s disease by inhibiting Tau protein aggregation has not been profoundly investigated. Hence, in this study, small-sized (PLGA) nanoparticles were fabricated through the stirring method. BSc3094 was loaded into the nanoparticles (PLGA@BSc). To further enhance the brain entry efficiency of PLGA nanoparticles, a pathological BBB-targeting peptide was modified on the surface to obtain PLGA@BSc@K. In this study, the stability, cytotoxicity, and pathological targeting of the nanosystem were characterized. The particle size of the nanosystem was about 90 nm, which was negatively charged. The results demonstrated that the particle size of the nanoparticles did not fluctuate conspicuously within 168 h, and the stability was favorable. PLGA and BSc3094 had no notable impact on cell viability and displayed low cytotoxicity. At 1 and 4 h, it was observed that the uptake of targeted modified nanoparticles by cells in pathological states augmented, suggesting that PLGA@BSc@K had an excellent pathological blood-brain barrier targeting effect. This study provides a novel concept for the targeting of BSc3094 nanoparticles in the brain and the treatment of Alzheimer′s disease.

In order to improve the operation difficulties in the narrow space of the nasal maxillary sinus, the nasal continuum minimally invasive surgical robot system is designed. The ball-and-socket joints and NiTiNol tubes are used as the main body of the continuum structure to improve the degree of freedom. The hardware systems and software systems are designed. The security control policies are planned. Finally, the robot confirmed prototype experiments are conducted and the feasibility of continuum robot confirmed through master-slave control experiment and animal experiment.
Animals ; Biomechanical Phenomena ; Equipment Design ; Minimally Invasive Surgical Procedures ; Robotic Surgical Procedures ; Robotics ; Software

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.