Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Objective:To investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for hepatocellular carcinoma (HCC) larger than 7 cm with portal vein tumor thrombosis (PVTT).Methods:The data from patients diagnosed with HCC (>7 cm) and PVTT who received either Len+DEB-TACE+HAIC ( n=99) or Len+DEB-TACE ( n=102) between July 2019 and June 2021 at six institutions in China were collected and retrospectively analyzed. Tumor responses were evaluated based on modified Response Evaluation Criteria in Solid Tumors. Objective response rate (ORR), disease control rate (DCR), time to progression (TTP), overall survival (OS), and treatment-related adverse event (TRAE) were compared between the two groups by propensity score matching. Subgroup analyses were performed for TTP and OS. Results:After propensity score matching, 83 pairs of patients were included in the study cohorts. The ORR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 66.3% and 38.6% ( χ2=12.78, P<0.001), respectively. The DCR for the Len+DEB-TACE+HAIC group and the Len+DEB-TACE group was 91.6% and 79.5% ( χ2=4.87, P=0.027), respectively. The median TTP and median OS for the Len+DEB-TACE+HAIC group were significantly longer than those for the Len+DEB-TACE group (TTP, 10.1 months vs. 6.1 months, χ2=35.28, P<0.001; OS, 17.3 months vs. 12.9 months, χ2=16.84, P<0.001). The incidence of ≥grade 3 TRAEs was 38.6% in the Len+DEB-TACE+HAIC group and 33.7% in the Len+DEB-TACE group ( χ2=0.42, P=0.518). Conclusion:Compared with Len+DEB-TACE, Len+DEB-TACE+HAIC led to improved tumor response, TTP and OS with an acceptable safety profile in patients with large HCC and PVTT.

AIM:To investigate the therapeutic effect of mitochondrial fission inhibitor-1(Mdivi-1)on experi-mental autoimmune encephalomyelitis(EAE)in mice,and to explore its mechanism.METHODS:The mice immunized with myelin oligodendrocyte glycoprotein peptide fragment 35-55(MOG35-55)were randomly divided into DMSO model group and Mdivi-1 intervention group.All mice were sacrificed on the 28th day after the first immunization.The demyelination was analyzed by Luxol fast blue staining.The protective mechanism of Mdivi-1 in the spinal cord tissue was investigated by immunofluorescence staining,TUNEL staining and the in vitro experiment with MO3.13 oligodendrocytes treated with staurosporine.The mitochondrial depolarization was detected by JC-1 staining,the cell injury was checked by LDH leakage,and the viability of MO3.13 oligodendrocytes was determined by MTT assay.RESULTS:Compared with DMSO model group,the demyelinating injury was alleviated and the proportion of apoptotic CC1+ oligodendrocytes in Mdivi-1 group was decreased.The cleaved caspase-3,caspase-9,cytochrome C and Bax protein expression levels in the spinal cord of Mdivi-1-treated mice was also attenuated.The in vitro MO3.13 cell experiments suggested that Mdivi-1 inhibited MO3.13 cell mitochondrial depolarization,attenuated the cell damage and increased the cell viability.CONCLUSION:Mdivi-1 pro-tects against the myelin injury in EAE mice,which may be related to the suppression of oligodendrocyte apoptosis.

【Objective】 To explore the effect and mechanism of Fasudil in the treatment of experimental autoimmune myocarditis (EAM) in mice so as to provide a theoretical basis for the clinical use of Fasudil in treating myocarditis. 【Methods】 Balb/c male mice were used as the research objects, and the EAM mice model was constructed using MyHC-α614-629 polypeptide. Mononuclear cells were isolated and cultured to detect the number of mononuclear cells in mouse spleen. Inflammation infiltration, fibrosis and IL-6 expression in mouse myocardial tissue were detected by HE staining, Masson staining and immunohistochemistry, respectively. The protein expressions of Notch1 and IL-6 were detected by Western blotting. qRT-PCR was used to detect the expressions of pro-inflammatory factors (IL-1α, IL-1β and IL-6) as well as key genes of TLRs and NOTCH signaling pathway. 【Results】 EAM mice showed increased HW, decreased BW, increased HW/e-BW, and increased inflammatory infiltration and fibrosis in myocardial tissue. The above-mentioned symptoms or pathological features were improved in EAM mice treated with Fasudil. The analysis showed that the pro-inflammatory factors IL-1α, IL-1β and IL-6 in the myocardial tissue of EAM mice were significantly increased, but only the expression of IL-6 was statistically different after Fasudil treatment compared with the control group. In addition, TLRs signaling pathway might also play an important role in the EAM mice treated with Fasudil. The expressions of IL-6 and Notch1 were consistent, and the expressions of the key genes of NOTCH signaling pathway (Notch1, Hes1 and Jag2) were down-regulated after Fasudil treatment. 【Conclusion】 Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice.

Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alterna-tives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.

Erythrocytes (red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems (DDS) because of their features of biocompatibility, biodegradability, and long circulating half-life. Accordingly, a "camouflage" comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection into the blood of animal models, the coated nanoparticles imitate RBCs and interact with the surroundings to achieve long-term circulation. In this review, the biomimetic platform of erythrocyte membrane-coated nano-cores is described with regard to various aspects, with particular focus placed on the coating mechanism, preparation methods, verification methods, and the latest anti-tumor applications. Finally, further functional modifications of the erythrocyte membranes and attempts to fuse the surface properties of multiple cell membranes are discussed, providing a foundation to stimulate extensive research into multifunctional nano-biomimetic systems.

Objective To evaluate the application effect of"2+2"medicine-education cooperation talents training mode. Methods The nursing undergraduates of 2013 grade were divided into the experimental and control group. The"2+2"medicine-education cooperation talents training mode was adopted in the former and traditional training model was used in the latter. The final examination scores of the fifth and sixth semester, scores of graduation examination, scores of the Nurse Competence Scale were compared between the two groups. Results There was no difference of scores of theory examination between the two group except the Nursing Professional English whose scores were higher in the control group. The practical skills exam scores of Medical Nursing, Surgical Nursing, Paediatric Nursing, Nursing of Gynecology and Obstetrics, Emergency Nursing, Rehabilitation Nursing, Community Nursing in the experimental group were 89.32 ± 6.02, 89.46 ± 5.29, 88.06 ± 6.34, 89.32 ± 5.58, 83.99 ± 6.44, 82.58 ± 5.78, 83.56±6.12, the control group were 87.72±5.90, 87.85±6.32, 85.59±5.79, 87.45±5.65, 81.82±6.06, 80.34± 5.89, 81.28±5.42, and the differences were statistically significant (t=2.052-3.261, P<0.05). The total and practical skills scores of graduation examination in the experimental group were 82.86±4.92, 85.60±4.54, which were 81.07 ± 5.52, 84.07 ± 4.59 in the control group. There were significant differences between the two groups (t=2.060, 2.011, P<0.05). The total score of Nurse Competence Scale and scores of the four dimensions of Teaching-coaching, Managing situations, Ensuring quality, Work role were 74.95 ± 3.40, 76.38 ± 3.98, 75.49 ± 3.23, 75.42 ± 2.72, 77.49 ± 2.76 in the experimental group, the control group were 73.63 ± 4.39, 72.90 ± 4.23, 74.12 ± 4.19, 74.32 ± 3.36, 76.46 ± 3.24, respectively. The differences were statistically significant (t=2.021- 2.492, P<0.05). Conclusions The"2 + 2"medicine- education cooperation talents training mode is proved to be an effective way to train nursing applied talents to meet regional demands. It could improve the hospital′s synthetic strength including health care quality and teaching ability, promote the development and construction of the nursing specialty and train the double-certificate teachers.

Objective To evaluate the effect of dexmedetomidine on the postoperative pulmonary function in patients undergoing laparoscopic operation.Methods Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 45-64 yr,weighing 45-70 kg,undergoing laparoscopic radical resection of rectal cancer,were divided into 2 groups (n =40 each) using a random number table:control group (group C) and dexmedetomidine group (group Dex).General anesthesia combined with epidural anesthesia was used.In group Dex,dexmedetonidine was intravenously infused as a bolus of 0.3 μg/kg over 10 min after epidural catheterization and before induction of general anesthesia,followed by an infusion of O.4 μg · kg-1 · h-1 starting from the end of tracheal intubation until 30 min before the end of operation.The equal volume of normal saline was given instead in group C.After epidural catheterization and before infusion of dexmedetomidine (T0),immediately before termination of pneumoperitoneum (T1) and at 1,6 and 24 h after operation (T2-4),blood samples were taken from the peripheral vein for determination of concentrations of serum interleukin-6 (IL-6),IL-10,tumor necrosis factor-alpha and malondialdehyde,and arterial blood gas analysis was performed simultaneously.Respiratory index and oxygenation index (OI) were calculated,and the occurrence of OI ≤ 300 mmHg was recorded.Results Compared with group C,the serum IL-6 and tumor necrosis factor-alpha concentrations and respiratory index were significantly decreased,and IL-1O concentrations and OI were increased at T1-4,and malondialdehyde concentrations were decreased at T1-3,and the incidence of OI ≤ 300 mmHg was decreased in group Dex (P＜0.05).Conclusion Dexmedetomidine can inhibit inflammatory responses and improve the postoperative pulmonary function in patients undergoing laparoscopic operation.

In recent years ,as a novel drug delivery system ,gold nanoparticles have attracted widespread attention .Be-cause of their special physicochemical properties ,such as quantum size effect ,unique optical phenomenon ,easily reacting with thiol compounds or disulfides and so on ,gold nanoparticles can delivery variety of types of drugs ,like proteins ,nucleic acid , small molecular drugs ,therefore they can be applied in tumor treatment and detection .In this paper the preparation of drug-loading gold nanoparticles ,their drug-loading ways and safety issues were reviewed .