Objective To investigate the inhibitory effect of anlotinib combined with anti-PD1 antibody on a colon cancer mouse model,and to explore its possible mechanismfor remodeling the immune system and tumor microenvironment.Methods A BALB/c mouse model was established with colon cancer cells CT26,and the mice were divided randomly into four groups:the control group,the anlotinib group,anti-PD1 antibody group and anlotinib combined with anti-PD1 antibody group,with 6 mice in each.During the experiment,tumor volumes were measured every 2 days using a vernier caliper.After the experiment(on day 14),the weight of the tumors of mice in each group was measured.Flow cytometry was used to detect changes in the number of immune infiltrating cells in tumor tissues,including CD4+T cells,CD8+T cells,monocytic myeloid-derived suppressor cells(M-MDSCs),granulocytic myeloid-derived suppressor cells(G-MDSCs),and M2-type tumor-associated macrophages(M2-TAM).Furthermore,ELISA was employed to detect the levels of vascular endothelial growth factor(VEGF),interferon-γ(IFN-γ),interleukin-17(IL-17),and IL-10 in the serum of mice.Results Compared with the control group,the other three groups showed a decrease in the volume and weight of transplanted tumors in mice(P＜0.05),as well as decreased levels of cytokines VEGF,IL-10(P＜0.05),and IL-17(P＜0.01).Additionally,there was an increase in the level of IFN-γ(P＜0.05).In terms of the number of immune infiltrating cells,the number of M-MDSCs decreased in each treatment group compared to the control group,but without statistically significant difference(P＞0.05).In the combined group,the number of M2-type TAMs decreased compared to the control group and the anti-PD-1 antibody group(P＜0.05).Furthermore,flow cytometry results indicated that compared to the control group,the other three groups showed an increase in the number of CD8+T cells in mice(P＜0.05).The number of CD4+T cells decreased slightly compared to the other groups,but the statistically significant difference was only observed when compared to the anlotinib group(P＜0.05).Conclusion The combination ofanlotinib and anti-PD1 antibody may regulate the levels of cytokines VEGF,IFN-γ,IL-10,and IL-17,thereby influencing the number of immunosuppressive cells in the tumor microenvironment.The tumor microenvironment and immunity can also be improved,thus significantly inhibiting the growth ofmouse colonic transplant tumors.

TCM dispensing is the most basic clinical pharmaceutical work of TCM.In recent years,based on the 9 key technologies of TCM dispensing,the TCM dispensing industry has ushered in great development,and innovative TCM dispensing information system and intelligent dispensing equipment have appeared.This article sorted out the current situation of TCM dispensing industry and looked forward to its future development route.The results showed that the introduction of new technology and new equipment in the key technical links of procurement acceptance,dispensing review,TCM decocting,medication guidance and so on have improved the quality of dispensing service and ensured the quality and safety of medication.In the development of modern TCM dispensing industry,it is necessary to improve the quality control standard system,service standard system and core equipment standard system in the standardization of dispensing technology;in terms of talent cultivation in the field of dispensing,it is necessary to focus on restructuring and building new educational models to cultivate new medical talents that intersect medical and engineering fields;in terms of informatization and intelligence,it is necessary to develop intelligent equipment that is more in line with the characteristics of TCM,and further promote and improve the"shared TCM pharmacy"model.Through improving the content of TCM clinical pharmaceutical care,developing new technology and equipment of TCM dispensing,and improving the level of dispensing service and education,it is expected to gradually realize the standardization,informatization and intelligent development of modern TCM dispensing industry.

OBJECTIVE: In order to solve the technical problems, clinical researchers face the process of medical imaging analysis such as data labeling, feature extraction and algorithm selection, a medical imaging oriented multi-disease research platform based on radiomics and machine learning technology was designed and constructed. METHODS: Five aspects including data acquisition, data management, data analysis, modeling and data management were considered. This platform provides comprehensive functions such as data retrieve and data annotation, image feature extraction and dimension reduction, machine learning model running, results validation, visual analysis and automatic generation of analysis reports, thus an integrated solution for the whole process of radiomics analysis has been generated. RESULTS: Clinical researchers can use this platform for the whole process of radiomics and machine learning analysis for medical images, and quickly produce research results. CONCLUSIONS This platform greatly shortens the time for medical image analysis research, decreasing the work difficulty of clinical researchers, as well as significantly promoting their working efficiency.
Machine Learning ; Diagnostic Imaging ; Algorithms ; Radiography

Objective: To evaluate the clinical efficacy and adverse events of recombinant human interleukin-11(rhIL-11) in the prevention of thrombocytopenia induced by craniospinal irradiation. Methods: In this randomized control study, 100 patients were randomly divided into A (rhIL-11 group, n=50) and B groups (control group, n=50). In the A group, subcutaneous injection of rhIL-11 was delivered at a dose of 50 μg/kg/d, once daily when the platelet count was< 100×10⁹/L during radiotherapy or decreased by> 50% compared with the baseline level. The administration of rhIL-11 was terminated when the platelet count was ≥ 200×10⁹/L. In the B group, the same protocol was conducted when the platelet count was< 50×10⁹/L and terminated until the platelet count was ≥ 100×10⁹/L. The clinical efficacy was assessed in 92 patients. Subcutaneous injection of rhIL-11 could significantly elevate the minimal platelet count during craniospinal irradiation (P<0.01), considerably shorten the duration of thrombocytopenia (P<0.01) and effectively shorten the duration of radiotherapy (P<0.01). Main adverse events included mild pain at the injection site, sclerosis, redness and fatigue, etc. Conclusions Injection of rhIL-11 can significantly enhance the platelet count, effectively reduce the incidence of thrombocytopenia throughout craniospinal irradiation, guarantee the success of radiotherapy and yield mild adverse events.

Objective To investigate the changes in the expression of phosphatidylinositol 3?kinase(PI3?K),mammalian target of rapamycin (mTOR)and Beclin?1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion ,so as to explore the role of PI3K/mTOR/autophagy pathway in global cerebral ischemia/reperfusion injury aggravated by intermittent hypoxia. Methods A total of 80 healthy male Wistar rats were randomly divided into sham operation group(SO group,n=20),merely ischemia/reperfusion group(I/R group,n=20),intermittent hypoxia for 7?day ischemia/reperfusion group(IH7+I/R group,n=20),and intermittent hypoxia for 21?day ischemia/reperfusion group(IH21+I/R group,n=20). IH7+I/R group and IH21+I/R group were respectively given intermittent hypoxia for 7 days and 21 days before ischemia/reperfusion. The cerebral ischemia/reperfusion model was established by modified Pulsinelli four?vessel occlusion method. The morpholog?ical changes of nerve cells in hippocampal CA1 region were observed by HE staining and electron microscope. The protein expressions of PI3?K, mTOR and Beclin?1 of nerve cells in hippocampal CA1 region were detected by immunohistochemical staining and RT?PCR. The learning memory capacity of rats were assessed by the Morris water maze test. Results Compared with SO group,I/R group increased the never cells morphology damages,reduced the number of survival neurons,and declined the ability of learning and memory(P<0.05). Immunohistochemistry showed that the number of PI3?K immunoreactive cell,mTOR immunoreactive cell and Beclin?1 immunoreactive cell increased in I/R group compared with S0 group(P<0.05). RT?PCR showed that the expressions of PI3?K,mTOR and Beclin?1 increased in I/R group compared with S0 group(P<0.05). Compared with I/R group,intermittent hypoxia groups increased the never cells morphology damages,decreased the number of survival neu?rons,and declined the ability of learning and memory(P<0.05). Immunohistochemistry showed that the number of PI3?K immunoreactive cell, mTOR immunoreactive cell and Beclin?1 immunoreactive cell increased in IH7+I/R and IH21+I/R groups compared with I/R group(P<0.05). RT?PCR showed that the expressions of PI3?K,mTOR and Beclin?1 increased in IH7+I/R and IH21+I/R groups compared with I/R group(P<0.05),and the changes were more significant in IH21+I/R group(P<0.05). Conclusion Intermittent hypoxia can aggravate neurological injury after ischemia,which is related to PI3K/mTOR/autophagy pathway activation.

Objective:To study the effect of endothelin receptor antagonist BQ-123 on the nerve function damage after subarachnoid hemorrhage (SAH)in the rats,and to explore the mechanisms.Methods:Total 120 male SD rats were divided into sham group,SAH group,low dose of BQ-123 group (50 μg· kg-1 )and high dose of BQ-123 group (75 μg·kg-1 ).The SAH rat models were established by injecting the autologous blood into cisterna magna twice.The morphological changes of hippocampus nerve cells of rat brain tissue were detected with HE staining, and the expressions of mTOR, Beclin-1 and LC3-Ⅱ in the hippocampus of rats were detected with immunohistochemistry and RT-PCR;the shuttle-box experiment was used to evaluate the abilities of learning and memory,and the holding power evaluation was used to evaluate the forelimb pulling force of the rats in various groups at each time point.Results:Compared with sham group,the morphological damages of neurons of the rats in SAH group were increased,the survival rate of neurons of the rats in SAH group was decreased (P <0.05),the expression levels of mTOR mRNA,Beclin-1 mRNA and LC3-Ⅱ mRNA in hippocampus tissue of the rats were increased (P < 0.05),and the abtilities of learning and memory and the values of holding power were decreased (P <0.05).Compared with SAH group,the morphological damages of neurons of the rats in BQ-123 groups were decreased,the survival rates of neurons of the rats in BQ-123 groups were increased (P < 0.05),the expression levels of mTOR mRNA of rats were decreased (P <0.05),the expression levels of Beclin-1 mRNA and LC3-ⅡmRNA in hippocampus tissue were increased (P <0.05),and the abilities of learning and memory and the values of holding power were increased (P < 0.05 ). The changes were more significant in high dose of BQ-123 group compared with low dose of BQ-123 group (P <0.05).Conclusion:BQ-123 can improve the nerve function damage after SAH in the rats,its mechanism may be related to regulating the mTOR/autophagy signaling pathway.

Objective To investigate the effect of obstructive sleep apnea hypoxia on learning memory capacity in rat after ischemia.Methods Eighty healthy male wister rats were randomly divided into:sham operation group (SO group,n =20),merely ischemia group (I/R group,n =20),and obstructive sleep apnea hypoxia for 7 days ischemia group (IH7 + I/R group,n =20),obstructive sleep apnea hypoxia for 21 days ischemia group (IH21 + I/R group,n =20).Obstructive sleep apnea hypoxia ischemia groups were respectively given obstructive sleep apnea hypoxia for 7 days and 21 days.Ischemia animals were prepared cerebral ischemia-reperfusion model by improved pulsinelli four vessels block (4-VO),the morphological changes of hippocampus nerve cells of rat brain were detected with HE,neuron pathology in hippocampal regin was observed using electron microscope,and learning memory capacity of rats were assessed by the Morris water maze test.Results Compared with the SO group,the I/R group demonstrated shortened escaping latency,increased frequency of crossing the platform in the water maze test,decreased survival rate of neurons,and increased apoptotic cells and ultrastructure damages (P ＜ 0.05).Compared with the I/R group,obstructive sleep apnea hypoxia ischemia groups showed shortened escaping latency,increased frequency of crossing the platform,decreased survival rate of neurons,and increased apoptotic cells and ultrastructure damages (P ＜ 0.05),especially in the IH21 + I/R group (P ＜ 0.05).Conclusions Obstructive sleep apnea hypoxia can increase the damage of learning memory capacity.This damage is related to hippocampus nerve loss and ultrastructure injury from obstructive sleep apnea hypoxia.

Objective To compare the changes in the expression of mTOR and beclin1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion,so as to explore the roles of mTOR/autophagy pathway in global cerebral ischemia/reperfusion injure aggravated by intermittent hypoxia.Methods One hundred healthy male Wistar rats were randomly divided into:sham operation group (SO group,n =20),intermittent hypoxia group (IH group,n =20),merely ischemia/ reperfusion group (I/R group,n =20),intermittent hypoxia ischemia/reperfusion group(IH + I/R group,n =20),intermittent hypoxia ischemia/reperfusion + mTOR inhibitor group (Inhibitor group,n =20).IH group,IH + I/R group and inhibitor group were respectively given intermittent hypoxia for 21 days before ischemia/ reperfusion.Ischemia animals were prepared cerebral ischemia-reperfusion model by improved pulsinelli four vessels block (4-VO),the morphological changes of hippocampus nerve cells of rat brain were detected with HE respectively 6,24 h after ischemia,and the expressions of mTOR protein and beclin1 protein in hippocampus of rat brain was detected with immunohistochemistry and RT-PCR respectively 6,24 h after ischemia.SPSS 17.0 software was used to analyze the data.Results Compared with the SO group,the IH group increased the never cells morphology damages and the empression of mTOR and beclin1 (q value was 32.94,47.31,63.68,78.45,all P ＜ 0.05);the I/R group increased the never cells morphology damages and the empression of mTOR and beclin1 (mTOR in I/R group:22.38 ±0.46,24.16 ±0.60;mTOR in SO group:14.65 ± 0.48,15.40 ± 0.58;beclin1 in I/R group:8.58 ± 0.58,10.58 ± 0.49;beclin1 in SO group:2.06 ±0.23,2.10 ±0.30;the differences were significant,q value was 90.59,106.83,95.88,119.44,all P ＜0.05).Compared with the IH group,IH + I/R group increased the never cells morphology damages and the empression of mTOR and beclin1 (q value was 152.23,165.61,135.01,156.48,all P ＜ 0.05).Compared with the I/R group,IH + I/R group increased the never cells morphology damages and the empression of mTOR and beclin1 (q value was 94.35,106.99,102.79,115.49,all P ＜0.05).Compared with the IH + I/R group,the inhibitor group decreased the never cells morphology damages and the expression of mTOR,increased the expression of beclin1 (mTOR in IH + I/R group:30.40 ±0.43,32.86 ±0.50;mTOR in inhibitor group:26.60 ±0.37,28.51 ±0.52;beclin1 in IH + I/R group:15.57 ± 0.57,18.78 ± 0.43;beclin1 in inhibitor group:21.74 ± 0.51,24.32 ± 0.49;the differences were significant,q value was 44.71,53.05,90.74,78.03,all P ＜ 0.05).Conclusion Intermittent hypoxia can aggravate the damage on nerve cells by activating mTOR/autophagy pathway after ischemia.

Objective To study the development characteristics of cavum sepit pellucidun (CSP)in prematures,neonates,infants and adults with MRI.Methods Brain MR images of different subjects including 141 prematures,106 neonates,171 infants and 35 046 adults were observed to determine the incidence and shape of CSP,and to measure its transverse diameter.Results CSP incidences were 100% (141/141)in prematures,97.17% (103/106)in neonates,2.26%(4/177)in infants and 0.82% (287/35 046)in adults respectively,and the CSP was cylinder (44.00%)or triangle in shape (56.00%)in prematures,triangle (76.40%)or fissure in shape (23.60%)in neonates.For infants or adults,each shape accounted for about a third of three kinds of shape respectively.Its mean transverse diameters were 5.7 mm in prematures,4.1 mm in neonates,13.3 mm in infants and 14.3 mm in adults respectivity.Conclusion CSP has different performances at development periods in human being brain.Most close after birth,while fewer remain in the whole life.

BACKGROUND:At present, the methods of treating unstable comminuted radial head fractures contain open reduction and internal fixation and metal prosthesis replacement. There were success cases treated by the two methods, but some shortcomings simultaneously existed.
OBJECTIVE:To compare the clinical therapeutic effects of replacement of the radial head with metal prosthesis with open reduction and internal fixation for the treatment of unstable comminuted radial head fractures.
METHODS:A prospective randomized control ed analysis was performed in 45 cases of unstable comminuted radial head fractures. These cases received open reduction and internal fixation and metal prosthesis replacement. This study compared the Broberg and Morrey elbow joint function score and the incidence of complications after fixation, and performed statistical analysis.
RESULTS AND CONCLUSION:The subjects were fol owed up for 1-5 years, averagely 2.8 years. According to Broberg and Morrey scores, the average score was 90.1 and the incidence of complications was 13.6%in the prosthesis replacement group. The average score was 76.8 and the incidence of complications was 47.9%in the open reduction. Significant differences were visible between the two groups (P<0.01). Compared with the open reduction group, prosthesis replacement for unstable comminuted radial head fractures obtained better joint function and lower incidence of complications.