Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin (DOX)-loaded methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) nanoparticles. Comparison of the kinetic profiles of both DOX and nanocarriers verifies the long-circulating effect, though of limited degree, as a result of pegylation. The nanocarrier profiles display fast clearance from the blood despite dense PEG decoration; DOX is cleared faster than the nanocarriers. The nanocarriers circulate longer than DOX in the blood, suggesting possible leakage of DOX from the nanocarriers. Hepatic accumulation is the highest among all organs and tissues investigated, which however is reversely proportionate to blood circulation time. Pegylation and reduction in particle size prove to extend circulation of drug nanocarriers in the blood with simultaneous decrease in uptake by various organs of the mononuclear phagocytic system. It is concluded that the long-circulating effect of mPEG-PCL nanoparticles is reconfirmed by monitoring of either DOX or the nanocarriers, but the faster clearance of DOX suggests possible leakage of a fraction of the payloads. The findings of this study are of potential translational significance in design of nanocarriers towards optimization of both therapeutic and toxic effects.

Objective : To explore the application of ZnxNi1－xS@ DOX nanostructures in combined photothermal- chemotherapy treatment of tumors，and to provide new ideas for the study of tumor treatment methods． Methods: The morphology and elementary composition of ZnxNi1－xS nanostructures were characterized by scanning emission e- lectron microscopy and other methods．The photothermal properties of ZnxNi1－xS nanostructures were explored by infrared thermal camera．The release of DOX under different temperature and pH was investigated by fluorescence spectrophotometer．The biosafety of ZnxNi1－xS nanostructures and the in vitro antitumor properties of ZnxNi1－xS@ DOX nanostructures were investigated by MTT assay. Results : The as-prepared ZnxNi1－xS nanostructure had good dispersion and uniform size．The ZnxNi1－xS nanostructures had good photothermal effect．The drug release behavior showed temperature and pH responsiveness．The MTT assay showed that ZnxNi1－xS nanostructures were nontoxic to normal cells．ZnxNi1－xS@ DOX nanostructures could significantly inhibit the growth of tumor cells under near-infra- red illumination． Conclusion The as-prepared ZnxNi1－xS nanostructure has good biocompatibility，on the basis of which the ZnxNi1－xS@ DOX nanostructures achieve good antitumor performance，which can be used for combined photothermal-chemotherapy treatment of tumors.

Objective:To evaluate the clinical outcome of the reconstruction of finger-pulp defects, using modified dorsal digital fasciocutaneous flap.Methods:Between June 2018 and March 2019, 14 patients with finger-pulp defects were admitted to the Department of Hand and Foot Surgery. There were 14 males and 2 females, aged from 27 to 63 years, with the mean age of 49 years. The defect areas of finger pulp were 1.6 cm × 1.4 cm-2.5 cm × 1.6 cm. All of the finger-pulp defects were treated by the modified dorsal digital fasciocutaneous flap and the inverted L-shaped incision was made at the distal part of the pedicle. The defects at donor sites were reconstructed with full-thickness skin grafts harvested from the forearm. Viability of the flap was recorded postoperatively. At the last follow-up, aesthetics, sensibility of the flap and hand performance were assessed.Results:All of the 14 flaps survived successfully, the areas were 1.8 cm×1.6 cm-2.7 cm×1.8 cm. Partial distal blister occurred on the flap in only one case, which was solved by aspiration without surgical intervention. All cases acquired follow-up visits for 5 to 12 months with a mean time of 8.9 months. The texture of flaps was similar to surrounding skin and the shape of reconstructed finger pulp was satisfactory. According to the assessment of total active movement, the results were excellent in 9 fingers, good in 5 fingers. The 2-point discrimination of flap was 8 to 11 mm (mean, 9.9 mm).Conclusions:It is an effective and simple method for the reconstruction of finger-pulp defects using modified dorsal digital fasciocutaneous flap. The clinical effectiveness is definite.

Objective:To evaluate the clinical outcome of the reconstruction of finger-pulp defects, using modified dorsal digital fasciocutaneous flap.Methods:Between June 2018 and March 2019, 14 patients with finger-pulp defects were admitted to the Department of Hand and Foot Surgery. There were 14 males and 2 females, aged from 27 to 63 years, with the mean age of 49 years. The defect areas of finger pulp were 1.6 cm × 1.4 cm-2.5 cm × 1.6 cm. All of the finger-pulp defects were treated by the modified dorsal digital fasciocutaneous flap and the inverted L-shaped incision was made at the distal part of the pedicle. The defects at donor sites were reconstructed with full-thickness skin grafts harvested from the forearm. Viability of the flap was recorded postoperatively. At the last follow-up, aesthetics, sensibility of the flap and hand performance were assessed.Results:All of the 14 flaps survived successfully, the areas were 1.8 cm×1.6 cm-2.7 cm×1.8 cm. Partial distal blister occurred on the flap in only one case, which was solved by aspiration without surgical intervention. All cases acquired follow-up visits for 5 to 12 months with a mean time of 8.9 months. The texture of flaps was similar to surrounding skin and the shape of reconstructed finger pulp was satisfactory. According to the assessment of total active movement, the results were excellent in 9 fingers, good in 5 fingers. The 2-point discrimination of flap was 8 to 11 mm (mean, 9.9 mm).Conclusions:It is an effective and simple method for the reconstruction of finger-pulp defects using modified dorsal digital fasciocutaneous flap. The clinical effectiveness is definite.

Objective:To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO) in the treatment of burn patients with acute respiratory distress syndrome (ARDS).Methods:The retrospective observational study and the systematic review were applied. From March 2014 to July 2020, five burn patients with ARDS received ECMO treatment in the First Affiliated Hospital of Army Medical University (the Third Military Medical University). All the five patients were male, aged from 40 to 62 years. The average total burn surface area was 58.8% total body surface area (TBSA) and four cases had severe inhalation injury. Patient's ECMO starting time, duration and mode, and whether successfully weaned or the cause of death, and others. were recorded. Furthermore, the changes of oxygenation and infection before, during, and after utilizing ECMO were analyzed. PubMed and Web of Science from the establishment of each database to August 2021 were searched using "Extracorporeal Membrane Oxygenation", "ECMO", "burn", "inhalation" as the search terms and "Title/Abstract" as the field to retrieve the clinical articles that meet the selection criteria . Basic information were extracted from the articles, including sample size, gender, age, total burn area, inhalation injury, the indication of ECMO, the start and lasting time of ECMO, ECMO mode, rate of successful weaning, complications of ECMO, mortality, the combined application of continuous renal replacement therapy (CRRT). Results:Five patients started venovenous ECMO on an average of 10.2 days after injury and lasted an average of 180.4 hours. Three out of 5 patients were weaned successfully with one patient survived. Four patients died of multiple organ dysfunction syndrome (MODS) and septic shock. Compared with those before ECMO treatment, the arterial oxygen partial pressure (PaO 2) and oxygen saturation in arterial blood (SaO 2) of three successfully weaned patients obviously increased during and after ECMO treatment. The fraction of inspired oxygen (FiO 2) decreased below 50% and PaO 2/FiO 2 ratio increased above 200 mmHg (1 mmHg=0.133 kPa) during and after ECMO. Furthermore, lactic acid and respiratory rate decreased, basically. Compared with those before ECMO, PaO 2 and SaO 2 in the other two patients during ECMO, who failed to be weaned, continuously decreased while lactic acid increased. Before and during ECMO, the PaO 2/FiO 2 ratios of unsuccessfullg weaned cases were less than 200 mmHg, and partial pressure of carbon dioxide in arterial blood (PaCO 2) were more than 40 mmHg. Compared with those before ECMO, there were no significant changes in body temperature during and after ECMO, which were less than 38 ℃. Compared with those before ECMO, the leucocyte number (the index without this in unsuccessfully weaned cases was omitted, the same as below) in four patients showed a significant decrease during ECMO, but rose after removal of ECMO. The proportion of neutrophils in three patients were slightly higher during ECMO than before ECMO, and did not change significantly after removal of ECMO. Compared with those before ECMO, platelet counts in three patients were significantly reduced during ECMO, and all five patients during ECMO were below normal levels. Compared with those before ECMO, the procalcitonin levels in four deaths were significantly increased during ECMO. Catheter culture of microorganism was performed in three successfully weaned patients, all of which were negative. A total of 13 literature were included, ranging from 1990 to 2019. The sample size in 6 studies was less than 10, and the sample size in 4 studies was between 10 and 20, and only 2 literatures had a sample size larger than 50. ECMO was applied in 295 burn patients with overall mortality of 48.8% (144/295), including 157 adults and 138 children. The most common indication of ECMO was severe ARDS. Among 157 adult burn patients (95 males and 65 females), 36 cases had inhalation injury. The average burn area was 27%-37%TBSA in 5 reported studies and was more than 50%TBSA in 2 reported studies. The most common mode was venovenous ECMO. ECMO treatment began 26.5 hours to 7.4 days after injury and lasted from 90 hours to 18 days, and the rate of successful weaning ranged from 50% to 100%. The most common complications were bleeding and infection. The mortality was 52.9% (83/157). MODS and sepsis were the leading causes of death. Among 138 pediatric burn patients (77 boys and 61 girls), 29 patients had inhalation injury. The average burn area was 17%-50.2%TBSA in 3 studies. ECMO treatment lasted from 165.2 hours to 324.4 hours. Bleeding was the most common complication. The mortality was 44.2% (61/138). Conclusions:ECMO is an effective strategy for the salvage treatment of burns complicated with ARDS. Furthermore, the prevention and treatment of bleeding, infection and organ dysfunction should be emphasized during the use of ECMO. More importantly, evidence-based guidelines for burns are urgently needed to further improve the clinical effect of ECMO.

Objective: To analyze the mutation of target genes in extranodal natural killer/T-cell lymphoma (ENKTL) by using nextgeneration sequencing, and to explore its relationship with prognosis and clinical characteristics, as to provide evidence for the pathogenesis, clinical diagnosis and targeted therapy of ENKTL. Methods: According to previous literature reports, the genes whose mutations can affect the development of lymphoma were selected as the target genes for this study. 29 patients with ENKTL, who were newly diagnosed at the Fourth Hospital of Hebei Medical University from August 2010 to October 2018, were selected for this study. The mutation of 9 target genes in the specimen was detected by thenext-generationsequencingtechnology.Therelationshipsamongclinicalfeatures,diseaseprognosisandmutationofthetargetgeneswereanalyzedbySPSS21.0statisticalsoftware.Results： ：Ninetargetgenes were were screened. AT-rich interactive-domain 1A(ARID1A) gene showed the highest mutation rate in ENKTL (10 cases, 34.48%) followedbylysinemethyltransferase2D(KMT2D)gene(31.03%)andtumorprotein P53 (TP53) gene (24.13%). Kaplan-Meier survival analysis showed that the overall survival of ENKTL patients with KMT2D gene wild type was significantly better than patients with KMT2D gene mutation (P=0.006). The KMT2D gene mutation was found to besignificantlyrelatedtoclinicalstage,CRP,albumin,lymphocyte count and Ki67 expression in ENKTL patients (all P<0.05). COX regression analysis showed that KMT2D gene mutation was an independent adverse prognostic factor (P<0.05). Conclusion: The KMT2D gene has a high mutant frequency in ENKTL and is associated with patients’prognosis, suggesting that KMT2D gene plays an important role in the initiation and development of ENKTL. It could be used as a clinical therapeutic target for ENKTL.

Objective To observe the application of allopurinol in the treatment of gouty nephropathy, and evaluate its clinical effect on the level of serum creatinine and urea nitrogen. Methods Patients with gouty nephropathy from April 2015 to May 2017 in Xining first people's hospital 126 patients as the research object, divided into observation group and control group of 63 cases with double blind random method, given the reference group of patients basic treatment, the observation group treated with allopurinol in the reference group on the basis, effects were compared between the two groups the clinical therapeutic effect and serum creatinine and blood urea nitrogen, blood pressure level. Results After 12 months of therapy, compared two groups of patients before treatment, serum uric acid, creatinine, blood urea nitrogen, blood pressure (systolic blood pressure, diastolic blood pressure) were improved, and the observation group was obviously better than that of control group (P<0.05); the observation group total efficiency of treatment group was 88.89％ (56/63), the reference group was 74.60％ (47/63), with significant difference between two groups (P<0.05). Conclusion Allopurinol can be used in the treatment of gouty nephropathy. It can help to improve the clinical effect and improve the clinical symptoms of the patients. It is of practical value.

Objective To evaluate the clinical efficacy of the over-the-scope-clip (OTSC) for endoscopic closure of acute refractory non-variceal upper gastrointestinal bleeding. Methods This retrospective study selected 16 refractory patients, including 2 cases with Mallory-Weiss syndrome, 7 cases with gastric ulcer, 1 case with gastric carcinoma and 6 cases with duodenal ulcer, underwent OTSC treatment of acute non-variceal upper gastrointestinal bleeding from January 2015 to June 2016 as study subjects. Results All of the 16 patients with bleeding lesions were successfully controlled. The successful rate is 100.0%. The mean procedure of OTSC for endoscopic bleeding closure was between 5.0 and 6.0 min. Conclusion The Over-the-Scope-Clip system is safe and effective for closure of acute non-variceal upper gastrointestinal bleeding in refractory patients, and deserves further clinical applications.