Objective To develop a cancer cell targeting probe based on silica-coated gold nanorods and investigate its optics properties and its targeting effect on human hepatocellular carcinoma HepG2 cells in vitro.Methods Preparation of gold nanorods (GNRs) by seeded growth method,and then the spherical core-shell silica-coated gold nanorods were successfully prepared by a sol-gel method,finally the GNRs@SiO2 was conjugated with folate (GNRs@SiO2-FA).The characteristics of GNRs@SiO2-FA were studied using transmission electron microscopy,and UV spectra.The cells were divided into 2 groups randomly,adding GNRs@SiO2-FA and GNRs solution respectively at the gold concentration of 40.0 × 10-6,20.0 ×10-6,10.0 × 10-6,5.0 × 10-6,2.5 × 10-6,and the MTT method was applied to detect the absorbance (A value) and study the cytotoxicity of GNRs@SiO2-FA and GNRs.The cells were divided into 2 groups randomly,and incubated with the same concentration of GNRs@SiO2-FA and GNRs@SiO2 solution respectively,at 2,4,8,16,24 h,and the targeting of GNRs@SiO2-FA cellular uptake were detected by ICPMS by observing the process of GNRs@SiO2-FA into the cells by transmission electron microscopy (TEM).The data represented by (-x) ± s ; single factor analysis of variance were compared between the 2 groups ; and the differences were significant when P ＜ 0.05.Results UV spectrum confirmed the successful preparation of GNRs@SiO2-FA.The A value of the same concentration group was variance analysised,and the differences between the 2 groups was statistically significant (all P ＜ 0.01) with the gold element concentration from high to low:F =191.876,265.419,77.987,52.061,18.745.The ICP-MS confirmed GNRs@SiO2-FA could specifically bind with HepG2 cells.GNRs@SiO2 group gold element content at 2,4,8,16,24 h was (256.7±3.3),(602.8±2.4),(1067.1±3.6),(1998.5±4.3),(2078.5±1.3) mg/kg and GNRs@SiO2-FA group was(693.1 ±2.0),(1432.0 ±2.6),(2331.3 ±3.5),(2484.5 ±5.0),(2589.7 ±2.1)mg/kg,and the 2 groups was statistically significant (F =3278.070,34287.199,85434.870,18333.454,42412.973,P ＜0.01).TEM results showed that a small amount of nano probes were in the cytoplasm after cultured with GNRs@SiO2-FA cells 1 h,and that,a lot of probe were in the cytoplasm,4-24 h later,but there was no probe in the nucleus.Conclusion The prepared Folate-conjugated gold nanorods has good performance on biocompatibility and targeting.

Walker carcinosarcoma 256 cells were injected intradermally into the medialaspect of right footpad of rats.After injection,the drained lymph nodes and overthe area of route of entry were examined microscopically in different period,inorder to determine the positive rate of appearance of cancer cells and metastasis inlymph nodes as well as other pathological changes.In the local area of inoculation cancer cells were noticed passing through spacesbetween the endothelial cells by ameboid movement into capillary lymph-vessels ormoved along with the lymph stream and get in to the capillary lymph-vessels fromtheir open ends.Individual or clumped cancer cells were seen in lymph-vesselsunder the epithelium and in the afferent lymph-vessels of lymph nodes.One hourafter the injection individual cancer cells were found first in the popliteal lymph nodes,then in the lumbar or renal lymph nodes on the third day.These cancer cellsappeared in the subcapsular sinuses at first,then in the intermediate and medullarysinuses subsequently and might be passed from one lymph node to another throughthe efferent lymph-vessels,for instance,cancer cells in popliteal nodes might migrateto lumbal or renal lymph nodes.When the cancer cells in lymph nodes became amass of a certain size associating with mitotic figures,a metastatic focus was thenestablished.Within twelve days after the inoculation,the total positive rates ofcancer cells and metastasis present in the popliteal lymph nodes were 59.5% and thetotal positive rate of multiple metastasis present simultaneously in several lymphnodes was 18.9 per sent.In addition to metastasis,these lymph nodes showed also themselves some im-mune changes,as including proliferation and enlargement of lymph follicles in cortex;widening of the paracortical area;ameboid movement present in different forms ofsmall lymphocytes and reticulosis,transformation of plasmacytes as well as increaseof immunoblasts.

Objective To evaluate the effect of oxytocin on Tp-e and QTc interval during caesarean section under spinal anesthesia in healthy puerperas. Methods Forty ASA Ⅰ puerperas were selected and allocated to receive oxytocin intravenous bolus group (group-IB) or oxytocin continuous infusion group (group-CI) with 20 puerperas in each by random digits table. An intravenous bolus of 5% glucose 5 ml and 5 U oxytocin was administered after delivery a 55-60 s period. A continuous infusion of 5% glucose 5 ml and 5U oxytocin was administered after delivery a 10 min period. Measured the QTc interval,Tp-e interval,mean arterial pressure (MAP) and beart rate ( HR ) pre-operatively, then 1,3 and 5 ain after spinal anesthesia, and at least 1,3,5 and 10 min after oxytocin injection. Results In group-IB:HR was fast 1 min after oxytocin injection compared with pre-operatively [(89 ± 13) beats/min vs. (73 ± 12) beats/min] ,MAP was decreased [(69 ± 12 ) mm Hg ( 1 mm Hg= 0. 133 kPa ) vs. ( 82 ± 13 ) mm Hg] and QTc interval was prolonged [(426 ±21 ) ms vs. (405 ± 18 ) ms] (P ＜ 0.01 ); but Tp-e interval was prolonged 1,3,5 min after oxytocin injection compared with pre-operatively (P ＜ 0.01 or ＜ 0.05 ). Conclusions Single large dose of oxytocin intravenous bolus (5 U) can prolong QTc interval and Tp-e interval in healthy puerperas, and Tp-e interval can exact predict the occurrence of ventricular arrhythmias. The risk-benefit balance of oxytocin bolus during caesarean delivery should be discussed with women with a history of long QT syndrome.

The incidence of skin disease is high, and outpatients have high demand for doctor-pa-tient communication. However, the education of doctor-patient communication for undergraduate student is very poor and almost absent for dermatology. For the stage of graduate study for dermatology, it is very im-portant to learn and grasp dermatology knowledge, to develop fundamental skill as a dermatologist, includ-ing the doctor-patient communication. In view of the problems such as short communication time, incomplete communication, and low specialization, we developed doctor-patient communication education norms for graduate students, to help graduate students majoring in dermatology to realize the importance of doctor-patient communication, pay attention to inquiry and communication about the disease associated with the system. We also strengthened the doctor-patient communication skills training in practice and achieved good results.

Objective:To observe the effect of a modified version of high-intensity interval training (HIIT) on the rehabilitation of persons with coronary artery disease (CAD), and to evaluate its safety and patient compliance.Methods:Sixty CAD patients were randomly divided into an exercise group and a control group, each of 30. Both groups were given conventional cardiac rehabilitation (including controlled nutrition, psychological counseling and low-intensity aerobic exercise). The exercise group additionally completed a session of HIIT twice a week for 6 weeks. Each session involved 30s of cycling at 85-90% of the patient′s maximum heart rate followed by 30s rest, repeated 15 times. The cardiorespiratory fitness, blood pressure, vascular function and body composition of both groups were documented before and after the 6 weeks. Compliance was recorded and the safety of the modified HIIT program was evaluated.Results:A significant improvement was observed in the maximum oxygen uptake and workload in a graded exercise test among the exercise group. The average blood pressure and body composition improved significantly, as did the average positive mood score and enjoyment of training. There was a significant decrease in negative mood and anxiety scores among the exercise group. No significant differences were observed in the control group. Compliance with the HIIT training program of the exercise group (97.4%) was significantly better than the control group′s compliance (88.7%) with its less strenuous regimen. There were no serious adverse reactions or cardiovascular events during the experiment.Conclusion:Modified HIIT is an effective form of cardiac rehabilitation training for CAD. It is safe, and compliance is good.

Objective To investigate the expressions of intercellular adhesion molecule (ICAM)-1 and matrix metalloproteinase (MMP)-2 in human gliomas and their correlation.Methods Sixty glioma samples,resected in our hospital from March 20,2010 to May 10,2014,were chosen in our study,and corroding to the WHO central nervous system tumor histological grading,they were divided into low-grade glioma group (grade Ⅰ-Ⅱ,n=26) and high-grade glioma group (grade Ⅲ-Ⅳ,n=34);other 10 normal brain tissues were used as controls.Reverse transcription-PCR and SP immumohistochemical staining were used to detect the ICAM-Ⅰ and MMP-2 mRNA and protein expressions.Results (1) The ICAM-1 and MMP-2 mRNA expressions in normal brain tissues,low-grade glioma group and high grade glioma group were increased in sequence,with significant difference (P＜0.05);the positive rate of ICAM-1 protein expression in normal brain tissues,low-grade glioma group and high grade glioma group was 20％,46.1％ and 88.2％,with significant differences (P＜0.05),and that in MMP-2 protein expression was 10％,50％ and 91.1％,with significant differences (P＜0.05).The mRNA expressions ofICAM-1 and MMP-2 in gliomas were positively correlated (r=0.702,P=0.001).Conclusions The expressions of ICAM-1 and MMP-2 are positively related to the malignant degrees of gliomas;the two may be useful reference factors to evaluate prognosis of human gliomas and potential targets for therapy.

Objective:To explore the impact of Cullin5 on the radiosensitivity of glioblastoma multiforme cell and its underlying mechanisms.Methods:Glioblastoma U251 cells were transfected with flag-NC plasmids and overexpression plasmids (flag-Cullin5), and divided into the flag-NC group and flag-Cullin5 group. The expression levels of Cullin5 and programmed death ligand 1 (PD-L1) mRNA and protein were assessed using real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. After exposing U251 cells to 0, 2, 4, and 8 Gy X-ray radiation, cell viability was evaluated via the CCK-8 assay, and apoptosis rates were measured using flow cytometry. Co-immunoprecipitation was used to detect the interaction between Cullin5 and PD-L1, and ubiquitination assays were conducted to investigate the ubiquitination effect of Cullin5 on PD-L1. Cells were further transfected with PD-L1 overexpression (oe-PD-L1) and flag-Cullin5 and assigned into the flag-Cullin5 group, flag-Cullin5+oe-NC group, and flag-Cullin5+oe-PD-L1 group. qRT-PCR and Western blot were used to measure the expression levels of Cullin5 and PD-L1 mRNA and protein post-X-ray radiation in these groups. Cell survival rates and apoptosis rates were measured following radiation. Statistical differences between two or among multiple groups were analyzed using LSD- t test or one-way ANOVA. Results:Compared with the flag-NC group, the flag-Cullin5 group showed increased expression levels of Cullin5 mRNA and protein, and decreased PD-L1 protein expression (all P<0.05). Following radiation doses of 4 and 8 Gy, there was a reduction in cell survival rates and an increase in apoptosis rates (both P<0.05). Co-immunoprecipitation assay revealed the presence of PD-L1 in the Cullin5 immunoprecipitate and vice versa. Ubiquitination levels of PD-L1 protein were higher in the flag-Cullin5 group compared to those in the flag-NC group. Additionally, compared to the flag-Cullin5 group, the flag-Cullin5+oe-PD-L1 group exhibited increased PD-L1 mRNA and protein levels (both P<0.05), and following radiation doses of 4 and 8 Gy, these cells showed higher survival rates and lower apoptosis rates (both P<0.05). Conclusion:Cullin5 enhances the radiosensitivity of glioblastoma multiforme cells to radiation therapy through mediating the ubiquitination degradation of PD-L1.

Objective:To analyze clinical manifestations, histopathological and pathogenic fungus characteristics as well as treatment of 3 cases of disseminated cutaneous alternariosis caused by Alternaria. Methods:Clinical data were collected from 3 cases of disseminated cutaneous alternariosis caused by Alternaria, who were diagnosed in Department of Dermatology, Xijing Hospital from 2019 to 2021, and clinical and histopathological features, fungal culture, strain identification and treatment results were retrospectively analyzed. Results:The 3 patients were aged 55, 41 and 46 years respectively, including 1 male and 2 females. Two patients were previously diagnosed with nephrotic syndrome and 1 with systemic lupus erythematosus. All the patients had a history of taking glucocorticoids and tacrolimus for different durations, and experienced chronic infections. Histopathological examination with hematoxylin and eosin (HE) staining showed double-contour thick-walled spores and knot-shaped thick-walled septal hyphae, but no melanin in skin lesions. Sequencing of the fungal internal transcribed spacer region confirmed that 2 cases were infected with Alternaria alternate, and 1 with Alternaria infectoria. Fungal culture at different temperatures showed that the growth ability of Alternaria markedly decreased at the temperature over 35 ℃. To treat these patients, the dose of tacrolimus was reduced to less than 1/3 of the standard dose, or tacrolimus was switched to other immunosuppressants, and systemic antifungal therapy was also given at the same time. After 7-month treatment, good clinical outcomes were achieved in the 3 patients. Conclusion:Disseminated cutaneous alternariosis is characterized by bilateral hematogenous dissemination and lymphatic distribution in unilateral limbs, and the skin lesions are characterized by verrucous plaques covered with scabs, nodules and/or sinuses.

Objective To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma ( FDCS ). Methods We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real?time PCR and EBER in situ hybridization was performed on 4 cases. Results Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low?grade FDCS and 3 cases of high?grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2?40, EGFR and CXCL13, but negative for S?100, CD68, HMB45, SMA, Desmin, CD117, Dog?1, CD34, CD30, EMA and CK.Five cases were positive for PD?L1 and the its expression in high?grade FDCS were higher than that in low?grade FDCS.Two cases of low?grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren′t detected in all of 7 cases. The result of EBER in?situ hybridization showed that only the nasopharynx FDCS was positive.The follow?up information of 5 patients were available (7～43 months), 4 patients died and 1 still alive with rectum metastasis.Conclusions FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first?line antibodies including CD21, CD23, CD35 and second?line antibodies including D2?40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD?L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.

Objective To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma ( FDCS ). Methods We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real?time PCR and EBER in situ hybridization was performed on 4 cases. Results Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low?grade FDCS and 3 cases of high?grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2?40, EGFR and CXCL13, but negative for S?100, CD68, HMB45, SMA, Desmin, CD117, Dog?1, CD34, CD30, EMA and CK.Five cases were positive for PD?L1 and the its expression in high?grade FDCS were higher than that in low?grade FDCS.Two cases of low?grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren′t detected in all of 7 cases. The result of EBER in?situ hybridization showed that only the nasopharynx FDCS was positive.The follow?up information of 5 patients were available (7～43 months), 4 patients died and 1 still alive with rectum metastasis.Conclusions FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first?line antibodies including CD21, CD23, CD35 and second?line antibodies including D2?40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD?L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.