Objective To investigate the expression of Cyclin F in clear cell renal cell carcinoma (ccRCC), its clinicopathological characteristics, and its effect on the biological behavior of renal cancer cell lines Methods RT-qPCR and Western blot were used to detect the mRNA and protein expression of Cyclin F in fresh ccRCC specimens. Immunohistochemistry assay was performed to detect the expression of Cyclin F protein in 80 paraffin samples. CCK-8 assay, scratch assay, and flow cytometry were conducted to determine the effects of Cyclin F overexpression on the proliferation, migration, and apoptosis of renal cancer cell lines. Results The expression of Cyclin F in cancer tissues was higher than that in adjacent tissues at the mRNA level (P<0.0285). The expression of Cyclin Fprotein in cancer tissues was lower than that in adjacent tissues (P<0.001). The analysis of clinicopathological parameters showed that the low expression of Cyclin F was correlated with WHO/ISUP grade, Ki67 index, and age (P=0.041, 0.047, 0.008,). In vitro experiments confirmed that overexpression of Cyclin F promoted the proliferation (P<0.001) and migratory ability (24 h P=0.003, 48 h P=0.0058) of the RCC 786-O cell line, while inhibiting apoptosis (P=0.0019). Conclusion The low expression of Cyclin F protein in ccRCC tissuesis associated with high ISUP grade, high Ki67 index, oldage, and prognosis of patients.

Secondary metabolites of medicinal plants are extremely important to human health because of their special pharmacological activities or efficacy. They are the main source of drugs, health care products, and cosmetics. As human beings continue to pursue health and longevity, the demand in the pharmaceutical market continues to grow. It becomes especially important to improve the production and quality of secondary metabolites of medicinal plants. Plant secondary metabolites are a kind of adaptation of plants to their environment and are the result of the interaction between plants and biotic and abiotic factors during the long-term evolution process. The production and accumulation of secondary metabolites in medicinal plants are mainly affected by plant genetic factors and environmental factors. Among them, light environment is extremely important for their synthesis. Therefore, light regulation has long been a research focus for many scholars in China and abroad. In this article, we the recent research progress on the effects of light regulation on the secondary metabolites of medicinal plants were reviewed, mainly focusing on the effects of light quality, light intensity and photoperiod, in order to provide theoretical basis and practical guidance for the efficient production of secondary metabolites with important pharmacological activities.

Intravenous thrombolysis and revascularisation are subject to strict time windows,and most patients still need to reperfuse ischaemic tissue through their own compensatory mechanisms due to subsequent re-occlusion or"no-reflow".A good collateral circulation can prolong the therapeutic window,increase the tolerance of brain tissue to ischaemia and hypoxia,and improve the prognosis,so promoting the establishment of collateral circulation to improve ischaemic tissue perfusion is a new idea in the treatment of ischaemic stroke.In this paper,we provides a review of relevant studies on methods of assessment of collateral circulation,therapeutic approaches,and clinical significance to provide guidance for the treatment of ischaemic stroke.

Objective To explore the toxicity of Polygonum multiflorum alcohol extract on 3D hepatospheres.Methods Variations in culture conditions and cell ratios were implemented,followed by the assessment of cell sphere diameter,density,and roundness,aiming to explore the optimal culture conditions.The 3D hepatocyte spheres were divided into control group and experimental-L,-M,-H groups.The experimental-L,-M,-H groups were treated with 0.25,1.00 and 2.50 mg·mL-1 Polygounm multiforum alcohol extract,and the control group was given the same amount of culture medium.The cell viability of the cell spheroids was tested by CellTiter-Glo reagent,the expression level of liver function related genes was detected by fluorescent quantitative polymerase chain reaction(RT-qRCR).The toxicity of cell spheres was detected by double fluorescent staining of living and dead cells.Results The ideal culture condition of cell sphere was 500 cells per micropore,and the cell ratio was HepG2-Huvec-LX-2=8∶1∶1.It displayed the values of 0.91±0.07 for circularity,0.91±0.02 for firmness,1.12±0.14 for aspect ratio,and(170.97±14.79)μm for diameter.On the 3rd,7th,10th and 14th days,the expression levels of albumin(ALB)mRNA were 1.00±0.02,0.96±0.02,0.54±0.07,0.52±0.07,and the expression levels of cytochrome P450 1A2(CYP1A2)mRNA were 1.00±0.10,2.15±0.16,2.45±0.33,1.30±0.03,respectively.The expression levels of multidrug resistance protein 2(MPR2)in the control group and the experimental-L,-M,-H groups were 1.00±0.31,1.38±0.24,1.48±0.06 and 1.90±0.08,respectively;spheroid viability were(98.19±0.49)％,(88.53±0.90)％,(71.60±2.91)％and(56.65±5.41)％.There were statistically significant differences in the above indexes between the experimental-L,-M,-H groups and the control group(all P＜0.05).Conclusion The established hepatocyte sphere co-culture model showed varying degrees of expression of phase Ⅰ/Ⅱ drug metabolism enzymes,transporters,and liver cell specific marker molecule albumin and can be used to evaluate the toxicity of multiflorum multiflorum,which provides further reference for the clinical application of multiflorum multiflorum.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

BACKGROUND: The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. METHODS: We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. RESULTS: All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. CONCLUSIONS Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
Humans ; Lung Neoplasms/metabolism* ; Interleukin-5/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Biomarkers ; Immunotherapy ; Disease Progression ; B7-H1 Antigen

ObjectiveSodium hyaluronate (HA) was used as the research object to modify it with phenolic acid in order to obtain the molecular structure with better antioxidant activity or even new activity. MethodsIn this study, 5 kinds of phenolic acid-sodium hyaluronate was prepared by free radical-mediated grafting method, and the grafts with the highest grafting degree were selected to optimize the synthesis conditions. Then, grafts structure and physicochemical properties were analyzed. The grafts were characterized by IR, UV, ¹H NMR, FESEM and TGA spectra. The in vitro antioxidant capacity of grafts was determined by the scavenging ability of DPPH·, ABTS⁺· and O^2-·. ResultsAmong 5 kinds of phenolic acid-sodium hyaluronate, the grafting rate of ferulic acid-sodium hyaluronate copolymer (FA-HA) was highest , which was chosen as experimental sample in the following tests. Firstly, the reaction conditions were investigated and the highest grafting rate was (16.59±0.31) mg/g at the optimal preparation conditions. Then, FA-HA structure and physicochemical properties were analyzed. Data from UV, IR, ¹H NMR analyses, TGA showed that FA were successfully grafted to HA. Compared with HA, the results of gel permeation chrematography (GPC) showed that the molecular mass distribution ofFA-HA copolymer decreased from 34.4 to 31.5 ku, but the uniformity of molecular distribution was improved. FESEM results showed that the structure of copolymer exhibited a closely connected lamellar structure with a relatively smooth surface. TGA results showed that thermal stability of FA-HA had a little decline. The antioxidant performance in vitro results showed that, during 0.25-10 g/L, FA-HA can eliminate (83.76±4.86)% DPPH·, (76.95±5.06)% ABTS⁺· and (83.08±2.51)% O^2-· respectively at 10 g/L. which were higher than that of native HA and FA. ConclusionFA and HA were successfully grafted together by free radical grafting, and the grafted FA-HA had better antioxidant activity in vitro, which provided a theoretical basis for further research and development of phenolic acid-HA grafts.

Objective:To carry out evidence-based nursing for standardized management of stress hyperglycemia in perioperative period of gastrointestinal tumor patients, and to formulate indicators, analyze obstacles and promoting factors, formulate action strategies.Methods:Guided by the Johns Hopkins evidence-based nursing model, evidence were searched, evaluated and summarized. Clinical indicators and review methods were formulated to carry out quality review. From November 2021 to April 2022, the medical staff and patients in the gastrointestinal surgery department of the First Affiliated Hospital of Anhui Medical University who met the inclusion criteria were conducted, and the incidence of compliance rate was calculated. Based on the results of the baseline review, the obstacles and contributing factors were analyzed.Results:A total of 26 pieces of best evidence were included and 14 indicators were formulated for 48 medical staff and 45 patients to clinical review, among which the compliance rate of 7 indicators was less than 60%. The main obstacle factors were lack of procedures and instruments for management of perioperative stress hyperglycemia in gastrointestinal tumor patients, lack of knowledge of medical staff, etc. The main promoting factors were organizational support, good atmosphere of medical team cooperation, strong willingness to change, etc.Conclusions:There is a big gap between the clinical practice and the best evidence of perioperative stress hyperglycemia management in patients with gastrointestinal tumor. Action strategies should be put forward for obstacles and promoting factors to promote evidence transformation.

The current situation of the construction and application of orthopaedic subspecialty nursing quality standards at home and abroad is reviewed, and the overview of orthopaedic subspecialty nursing quality standards, theoretical foundations, the content of the standard construction, the form and results of the application, and the shortcomings and outlooks are elaborated and illustrated, with a view to providing theoretical references for the further improvement and application of China′s orthopaedic subspecialty nursing quality standard system, and providing scientific suggestions and reflections for the promotion of the high-quality development of orthopaedic subspecialty nursing.

BACKGROUND:Autoimmune regulator gene(Aire)and Wnt signaling pathway play an important role in the maintenance and differentiation of mouse embryonic stem cell pluripotency.However,whether the Wnt signal and Aire are involved in the differentiation of embryonic stem cells to thymic epithelial progenitor cells remains poorly understood. OBJECTIVE:To investigate the relationship of the Wnt signaling pathway and Aire with the differentiation of embryonic stem cells. METHODS:A two-step differentiation method was used to induce mouse embryonic stem cells to differentiate into endoderm and then into thymic epithelial progenitor cells.Mouse embryonic stem cells were infected with Aire shRNA lentivirus,and monoclonal stable strains were screened by puromycin.Mouse embryonic stem cells were collected on days 0,3 and 10 of the directed induction of differentiation after the induced differentiation by the two-step differentiation method.Cellular immunofluorescence,flow cytometry,western blot assay,and real-time qPCR were used to detect the expression changes of related genes and proteins. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed positive expression of SSEA1 and OCT4 on day 0 of targeted induction of differentiation.(2)Immunofluorescence staining showed double-positive expression of SOX17 and FOXA2 on day 3 of targeted induction of differentiation.(3)Flow cytometry results showed positive expression of EPCAM1,K5 and K8 on day 10 of targeted induction of differentiation.(4)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,and Gsk-3β proteins were elevated,and the expression level of Aire protein was decreased in induced differentiated thymic epithelial progenitor cells.(5)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,Gsk-3β and Aire mRNA were elevated in thymic epithelial progenitor cells.(6)Compared with normal cultured mouse embryonic stem cells and their ultimately differentiated thymic epithelial progenitor cells,the expression levels of Wnt7a,β-catenin and Gsk-3β proteins were reduced in mouse embryonic stem cells with knockdown of Aire genes and their final differentiated thymic epithelial progenitor cells.In conclusion,the Wnt signaling pathway and Aire are jointly involved in the process of targeted induction of differentiation of mouse embryonic stem cells into mouse thymic epithelial progenitor cells.