Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

BACKGROUND:Iron overload refers to excessive accumulation of iron in the body,which can cause pathological changes in various tissues.At present,the molecular mechanism and potential gene targets related to iron overload in osteoarthritis still need to be further studied and explored. OBJECTIVE:To analyze the key genes of iron overload in osteoarthritis by means of bioinformatics and verify them in animal experiments,so as to provide a new idea for preventing and treating osteoarthritis from the perspective of iron overload. METHODS:GEO database and GeneCards database were used to screen out genes associated with osteoarthritis and genes associated with iron overload.Then,the intersection of the two was taken to obtain a collection of genes commonly associated with osteoarthritis and iron overload.GO and KEGG enrichment analyses were used to screen the functions and pathways of these genes.To further investigate the interactions between these genes,a protein-protein interaction network was constructed and five computational methods of Cytoscape software were utilized to identify the Hub genes for iron overload in osteoarthritis.Finally,12 male Sprague-Dawley rats were divided into osteoarthritis group and normal group,with 6 rats in each group.A knee osteoarthritis model was established by the modified Hulth method in the osteoarthritis group.The expression of Hub genes in the knee joint of rats in each group was detected by PCR. RESULTS AND CONCLUSION:(1)A total of 51 genes associated with iron overload were identified in osteoarthritis.GO enrichment analysis showed that these genes were mainly involved in cytokine receptor binding,chemokine receptor binding,cytokine activity,growth factor receptor binding and oligosaccharide binding.(2)KEGG enrichment analysis showed that genes associated with iron overload in osteoarthritis was mainly involved in tumor necrosis factor signaling pathway and lipid and atherosclerosis signaling pathway.(3)The protein-protein interaction network was constructed,and five Hub genes of iron overload,intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6,were obtained by further analysis.Animal experiments verified that there were significant differences in the expression of the above Hub genes in the rat knee joint between the control group and the experimental group(P<0.05).(4)All these findings show that intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6 can be used as the Hub genes of iron overload in osteoarthritis,which are expected to become new targets for the prevention and treatment of osteoarthritis.

[This corrects the article DOI: 10.1016/j.apsb.2021.11.009.].

Objective To investigate the potential medication risk by identifying and analyzing the features of liver-related adverse drug reaction (ADR) in pregnant women. Methods A retrospective study was performed for the reports on liver-related ADR in pregnant women from January 1, 2012 to December 31, 2016 in HILI Cloud (hilicloud.net). Main clinical features and medication rules were analyzed, and reporting odds ratio ( ROR ) was used to analyze the relative risk of related drugs. Results Methotrexate, mifepristone, and ritodrine were the high-frequency drugs reported for liver-related ADR in pregnant women and were mainly used for termination of ectopic pregnancy and treatment of hydatidiform mole. The relative risk analysis of liver-related ADR showed that in pregnant women, the use of methotrexate ( ROR =37.52, 95% confidence interval [ CI ]=31.35-44.89), progesterone ( ROR =7.33, 95% CI : 2.75-19.59), and dydrogesterone ( ROR =6.58, 95% CI : 2.20-19.69) was strongly associated with the risk of liver injury, and the association of methotrexate with the risk of liver injury in pregnant women was significantly stronger than that in non-pregnant women ( ROR =1.71, 95% CI : 1.47-4.36). Conclusion The potential risk of liver injury should be taken seriously in pregnant women using the drugs such as methotrexate and progesterone, so as to avoid serious adverse reactions.

Objective:To explore the feasibility and safety of long-distance urological nephrotomy with the support of 5G communication technology by using the domestic robot.Methods:Clinical data of the patients with remote robot-assisted laparoscopic nephrectomy, which were completed from March to April 2021 by the Affiliated Hospital of Qingdao University (as the host hospital where the main operating system located) were retrospectively analyzed. There were 3 patients, including 2 males and 1 female.The average age was 61 (49-73) years, and the average body mass index was 23.73 (20.00-27.76) kg/m 2. One patient had a ASA classification of grade 2, and the other 2 patients had grade 3. All patients met the surgical criteria for non-functional nephrectomy. The chief surgeon who performing the telesurgery was located at the Affiliated Hospital of Qingdao University. The surgeon remotely controlled the bedside operating system (slave system) in 3 local hospitals located in other cities in Shandong Province (network communication distances of 82.5, 141 and 229 km, respectively) by manipulating the master system located in Qingdao. Images and operating instructions during surgery were transmitted using 5G wireless communication technology. Intraoperative network conditions, robot operation, and patient perioperative data were summarized. Results:All 3 tele-nephrectomies were successfully completed. The average network signal latency time was 27.3 (23-30) ms, with no packet loss, and the average total latency time was 177.3(173-180) ms. The mean resection time was 79.3 (52-111) min, and the average intraoperative blood loss was 31.1 (15.6-41.9) ml. There were no network related adverse events occurred during the operation, and the robot-related adverse events occured 3 times, all three of which were characterized by inconsistent master and slave movements of the manipulator arm and the bedside robotic arm. None of these adverse events affected the successful performance of the telesurgery. The mean postoperative exhaust time was 60.5 (38.5-78.0) h. The mean postoperative VAS score at 24 hours was 3.7 (3-4). The Clavien-Dindo classification were all grade I. No significant abnormality was found on the 30th day after surgery, and the patients recovered well at the follow-up until 6 months postoperatively.Conclusions:It is safe and feasible to perform remote robot-assisted laparoscopic nephrectomy based on 5G communication technology with no serious adverse events or surgical complications.However, the conclusion needs to be further verified by large sample and multi-center prospective study.

Objective:To understand the personal dose level of nuclear medical workers in a hospital, and to provide basis for health management of nuclear medicine occupational population.Methods:From January 2014 to December 2018, 147 radiation workers in a hospital were selected as the monitoring objects, and the individual dose monitoring data were analyzed. The correlation between individual dose and clinical workload was analyzed.Results:The average annual personal dose of 147 staff members was below the national dose limit. Compared with the radiation department, the average annual personal dose of nuclear medical staff was higher, and the difference was statistically significant ( P<0.05) . There was a positive correlation between the annual average personal dose and the corresponding injection workload (Rs=0.69, P<0.05) . Conclusion:The occupational exposure risk of nuclear medical technicians and nurses is high, and reasonable protective measures should be taken to reduce the radiation exposure dose. Conclusion The occupational exposure risk of nuclear medical technicians and nurses is high, and reasonable protective measures should be taken to reduce the radiation exposure dose.

Objective:To understand the personal dose level of nuclear medical workers in a hospital, and to provide basis for health management of nuclear medicine occupational population.Methods:From January 2014 to December 2018, 147 radiation workers in a hospital were selected as the monitoring objects, and the individual dose monitoring data were analyzed. The correlation between individual dose and clinical workload was analyzed.Results:The average annual personal dose of 147 staff members was below the national dose limit. Compared with the radiation department, the average annual personal dose of nuclear medical staff was higher, and the difference was statistically significant ( P<0.05) . There was a positive correlation between the annual average personal dose and the corresponding injection workload (Rs=0.69, P<0.05) . Conclusion:The occupational exposure risk of nuclear medical technicians and nurses is high, and reasonable protective measures should be taken to reduce the radiation exposure dose. Conclusion The occupational exposure risk of nuclear medical technicians and nurses is high, and reasonable protective measures should be taken to reduce the radiation exposure dose.

Objective To investigate the influence of proinflammatory factor interleukin-18(IL-18) on vein endothelial cell function by activating NF-κB mediated cell signal pathway and its association with deep vein thrombosis(DVT).Methods Recombinant human IL-18 was used to act on in vitro cultured human umbilical vein endothelial cell(HUVECs).The NF-κB activation inhibitor was used to conduct interference.The detection measures of real time fluorescence quantitative PCR,Western blot,immunofluorescence and flow cytometry were used to verify whether IL-18 affect the expression of endothelial cellular function markers such as HUVECs normal statusand vWF,P-selectin and tissue plasminogen activator(t-PA) by activating NF-κB mediated cell signal pathway.Moreover the mechanism of IL-18 participating in the DVT was performed the comprehensive analysis by combining with previous study.Results IL-18 could activate NF-κB in endothelial cell,increased the p65 expression in nucleus,decreased the intracellular IκBα expression and significantly increased early apoptosis cells in HUVECs;adding QNZ(EVP4593) could significantly inhibit the activation effect of IL-18 on NF-κB,the occurrence of cellular injury and apoptosis was significantly reduced;IL-18 could promote the abnormal expression of DVT related endothelial cell markers vWF,P-selectin and t-PA (P<0.05).But various markers could recover conventional expression after inhibiting NF-κB activation.Conclusion The interaction between Il-18 and NF-κB causes the abnormality of HUVECs growth status and function,which may be the DVT onset related pathogenic mechanism.

Objective To investigate the correlation between IL‐18 and deep venous thrombosis disease and its clinical significa‐tion .Methods To detect the expression of IL‐18 by ELISA ,we collected the blood samples of DVT patients as the experimental group(n=40) compared to the control group(n=40) and normal group(n=20) .IL‐18 over expression/interference vectors were constructed and transfected human vein endothelial cells ,analyzed by microarray and KEGG Pathway as biology information tech‐nology .Then discuss the association between IL‐18 and DVT .Results Results of ELISA showed that compared with control group and normal group ,the expression of IL‐18 gene in DVT patient were up‐regulated(F=11 .248 ,P<0 .01) .Compared with normal group ,the IL‐18 expression in control group have not been significantly up‐regulated(P>0 .05) .Immunofluorescence detected IL‐18 gene expression in cytoplasm of human umbilical vein endothelial cells (HUVECs) .According to the microarray analysis we found in the IL18‐pCDH‐GFP transfected cells 17 signaling pathways were down‐expressed while 16 signaling pathways were up‐expressed .Compared with normal group cells ,in the IL18‐LMP‐shRNAmir1 transfected cells 23 signaling pathways were down‐ex‐pressed and 9 signaling pathways were up‐expressed .Conclusion Based on the above experimental data ,it is very clear that IL‐18 influenced HUVECs and plays an important role in DVT ,it is possible to predict the diagnosis of DVT and act as candidate molecu‐lar markers .