OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial （IIT）. METHODS With benchmarking analysis， based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai， a thorough review was conducted， involving relevant laws， regulations， and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects， a detailed comparative analysis of key processes was carried out， such as the receipt， storage， distribution， use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing， the training before project implementation was insufficient， and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems， improvement measures were put forward， including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs， etc. The related systems were improved， and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established， which helps to improve the institutional X2023076） framework of medical institutions in this field.

Abstract Low level light therapy utilizes the photochemical effect of red light to induce reactions in the irradiated body tissue to achieve the therapeutic effect. Myopia and amblyopia are diseases which threaten the eye health of children and adolescents. Red light has been used to treat amblyopia for decades. Recently, its application in myopia prevention and control has become a new hotspot. This review summarizes the application of low level red light in children and adolescents with myopia and amblyopia from the aspects of intervention mode, effect, factors, mechanism and safety to provide reference for future researches.

Isochrysis galbana is considered an ideal bait for functional foods and nutraceuticals of humans because of its high fucoxanthin(Fx)content.However,multi-omics analysis of the regula-tory networks for Fx biosynthesis in I.galbana has not been reported.In this study,we report a high-quality genome assembly of I.galbana LG007,which has a genome size of 92.73 Mb,with a contig N50 of 6.99 Mb and 14,900 protein-coding genes.Phylogenetic analysis confirmed the monophyly of Haptophyta,with I.galbana sister to Emiliania huxleyi and Chrysochromulina tobinii.Evolutionary analysis revealed an estimated divergence time between I.galbana and E.huxleyi of～133 million years ago.Gene family analysis indicated that lipid metabolism-related genes exhibited significant expansion,including IgPLMT,IgOAR1,and IgDEGS1.Metabolome analysis showed that the content of carotenoids in I.galbana cultured under green light for 7 days was higher than that under white light,and β-carotene was the main carotenoid,accounting for 79.09％of the total carotenoids.Comprehensive multi-omics analysis revealed that the content of β-carotene,antheraxanthin,zeaxanthin,and Fx was increased by green light induction,which was significantly correlated with the expression of IgMYB98,IgZDS,IgPDS,IgLHCX2,IgZEP,IgLCYb,and IgNSY.These findings contribute to the understanding of Fx biosynthesis and its regulation,pro-viding a valuable reference for food and pharmaceutical applications.

Objective:To investigate whether idebenone can improve behavioral disorders in mice with Parkinson disease (PD) by increasing PHB2 mediated mitophagy.Methods:In the first small experiment, thirty mice were randomly divided into normal control group, model group and treatment group according to the random number table method, with 10 animals in each group.The aim of this study was to observe the effect of idebenone on the behavior of Parkinson disease model mice. In the second experiment, 20 mice were randomly divided into blank control group, MPTP group, shRNA-PHB2 group and shRNA-PHB2+ MPTP group, with 5 mice in each group. The changes of tyrosine dehydrogenase (TH) in brain tissue were detected by immunofluorescence assay. In the third experiment, 30 mice were randomly divided into blank control group, shRNA-PHB2 group, MPTP+ idebenone group, shRNA-PHB2+ MPTP group, shRNA-PHB2+ idebenone group and shRNA-PHB2+ MPTP+ idebenone group, with 5 animals in each group. The aim of this study was to investigate the effect of idebenone on mitochondrial autophagy in mouse brain.C57BL-6 mice were intraperitoneally injected with MPTP to establish the animal model of chronic PD. Then 200 mg / kg idebenone was given by gavage for 21 days. And the expression of PHB2 in brain was inhibited by microinjection of adeno-associated virus 9 (AAV9) shRNA inhibin 2(PHB2) into lateral ventricle. The behavioral changes of the PD mice were detected by Morris water maze, and the changes of tyrosine dehydrogenase (TH) induced by inhibiting PHB2 were detected by immunohistochemistry. The protein expression of LC3 and PHB2 in substantia nigra of midbrain was detected by Western blot.The data were analyzed by GraphPad 7.0 and SPSS 22.0.Results:(1) In the water maze test data of the first small experiment, the repeated measurement ANOVA showed that the group-time interaction effects of latency of mice from 1 to 7 days were significant ( Ftime×group=20.51, P<0.05). Simple effect analysis showed that on the 5th, 6th and 7th day, the incubation period of the treatment group was significantly shortened (all P<0.05). Univariate analysis of variance showed that on the 7th day of the test, the differences between the control group and the model group, the model group and the treatment group, the control group and the treatment group were all statistically significant( t=-49.95, -21.81, 28.14; all P<0.01). In the third small experiment, repeated measurement analysis of variance showed that the interaction between time and group was significant ( Ftime×group=42.11, P<0.01). Simple effect analysis showed that compared with MPTP+ idebenone group, the latency of shRNA-PHB2+ MPTP+ idebenone group was significantly prolonged (all P<0.05). There were no significant difference between shRNA-PHB2+ MPTP+ idebenone group and shRNA-PHB2+ MPTP group except the 4th day ( P<0.05). On the 7th day, compared with MPTP+ idebenone group, the residence time of shRNA-PHB2+ MPTP+ idebenone group was significantly increased ( t=-34.36, P<0.001), but there was no significant difference between shRNA-PHB2+ MPTP group and shRNA-PHB2+ MPTP+ idebenone group ( t=2.94, P>0.05). (2)The results of immunofluorescence experiment showed that the relative expression of TH in the control group, model group, shRNA-PHB2 group and shRNA-PHB2+ MPTP group were (41.03±3.01), (24.20±4.18), (38.39±3.31) and (13.12±2.65), respectively. Compared with the control group, the expression of TH in the midbrain of the MPTP group was significantly down-regulated, the difference was statistically significant( t=7.98, P<0.01). Compared with the MPTP group, the expression of TH in shRNA-PHB2 group was down regulated ( t=-6.73, P<0.05). (3) Western blot results showed that the relative expression of LC3 in midbrain tissue of control group, shRNA-PHB2 group, MPTP+ idebenone group, shRNA-PHB2+ MPTP group, shRNA-PHB2+ idebenone group and shRNA-PHB2+ MPTP+ idebenone group were (0.86±0.07), (0.77±0.08), (0.42±0.05), (0.21±0.05), (0.66±0.09) and (0.27±0.07). The relative expression of PHB2 were (1.13±0.14), (0.56±0.11), (1.08±0.14), (0.27±0.07), (0.68±0.14) and (0.24±0.10). Compared with MPTP+ idebenone group, the relative expression of LC3 and PHB2 in shRNA-PHB2+ MPTP+ idebenone group was significantly decreased ( F=1.96, P<0.01). Conclusion:Idebenone can increase the level of mitophagy in PD mice through PHB2, thus improving the behavioral disorder.

Objective:To study the ability of the Retinal Health Assessment (RHA) system to obtain fundus images in patients with different types and degrees of cataracts.Methods:A cross-sectional study was performed.Forty-five eyes of 41 patients with cataract were enrolled in First People's Hospital, Shanghai Jiaotong University from December 2016 to January 2017.Lens opacity grading and RHA fundus imaging were performed after pupil dilation.Forty-five eyes were divided into 4 groups according to the degree of lens opacity: cortical cataract group 18 eyes, nucleus cataract group 21 eyes, posterior subcapsular cataract group 2 eyes, hybrid cataract group 4 eyes.Fundus images were obtained by FullSpectrum mode of RHA2020, and the clearness of fundus images was evaluated.Scores of fundus images clarity were compared between the cortical cataract group and nucleus cataract group.This study was approved by the Ethics Committee of First People's Hospital, Shanghai Jiaotong University.Written informed consent was obtained from each patient prior to any medical examination.Results:In all 45 eyes, the phacoscotasmus classification ranged from mildest (C0N2P0, 1 eye) to very serious (C2N5P2 and C4N2P4, 2 eyes). The grade Ⅳ nuclear opacity, grade Ⅲ cortical opacity, and grade Ⅲ posterior subcapsular opacity reduced the quality of RHA images significantly, especially for images with red and green light.In cortical cataract group, images showed peripapillary vessels and retinal vessels at 580 nm and 590 nm, while retinal and choroidal vessels, as well as choroidal pigmentation, were visible at 810 nm.The clarity scores at 580, 590 and 810 nm were 2.0 (1.0, 3.0), 2.0 (2.0, 3.0) and 2.0 (2.0, 3.0), which were lower than that with red and green light (620 nm + 550 nm) (3.0[2.0, 3.0]), with statistically significant differences (all at P<0.05). In nucleus cataract group, the quality of fundus images from the eyes with grade Ⅲ nucleus cataracts was good, the image quality decreased when the nucleus opacity was grade Ⅳ, retinal vessels were occasionally observed at 580 nm and 590 nm.Additionally, retinal and choroidal vessels and choroidal pigment were visible at 810 nm and 850 nm.The clarity scores at 580, 590, 810 and 850 nm were 1.0 (1.0, 3.0), 2.0 (1.0, 3.0) and 2.0 (1.0, 3.0), which were lower than that with red and green light (620 nm + 550 nm) (3.0[1.5, 3.0]), with statistically significant differences (all at P<0.05). In posterior subcapsular cataract group, the retinal vessels were visible at 580 nm, meanwhile retinal and choroidal vessels and choroidal pigment could be observed at 810 nm and 850 nm.In hybrid cataract group, running lines of retinal vessels could be seen at 850 nm, while the central reflection was absent.Focal choroidal vessels were observed. Conclusions:Except for severe cases, RHA system can produce good quality fundus images in cataract eyes at 580, 590, 810 and 850 nm, facilitating the evaluation of fundus disease before surgery and prediction of visual outcomes after surgery.

Objective To investigate the difference of styrofoam and breast carrier in postposition fixation of intensity-modulated radiotherapy after breast conservative surgery for breast cancer patients.Methods From February 2018 to August 2018,tweenty-four patients with breast cancer in Sun Yet-Sen Memorial Hospital of Sun Yet-sen University were selected for this study,who underwent hypofactionationed radiotherapy after breast conservative surgery with total dose 42.56 Gy/16Fractions.They were randomized into styrofoam test group and breastcarrier control group.Cone beam CT as used to record the positioning error under the directions of left and right (x),head and foot (y),abdomen and back (y) within two groups at the first,third,fifth,seventh,eleventh time before irradiation.Furthermore,the PTV extension margin was calculated and the positioning time of two groups was recorded.Two sets of pendulum errors were analyzed by independent sample T-test,and the outspread value of inter-fractional set up error of the PTV was calculated.Results The errors of the test group and the control group in the direction of x,y,z were as follows:(2.36±1.89) and (2.56±2.05) mm (P=0.49),(1.76± 1.78) and (3.28±2.79) mm (P＜0.05),(1.47± 1.49) and (1.73± 1.81) mm (P=0.28).The extension values of inter-fractional set up error of CTV to PTV were 2.97,2.92,2.21 mm and 3.41,4.09,2.59 mm respectively.The time of single positioning was (3.4± 1.1) and (5.5 ± 3.1) min respectively (P=0.01).Conclusion Styrofoam has better positioning accuracy and efficiency compared with breast carrier.

Objective: To preliminarily investigate the difference of position fixation accuracy between polyurethane styrofoam and vacuum negative pressure pad in intensity-modulated radiation therapy (IMRT) after radical mastectomy for breast cancer. Methods: Forty breast cancer patients, who received breast-conserving surgery followed by hyper-fractionated IMRT of the whole breast (42.56 Gy for 16 times) in our hospital between 2017 and 2018 were recruited and randomly divided into the polyurethane styrofoam group and vacuum negative pressure pad group. Before IMRT treatment, the anterior and lateral films of patients were taken with kilovoltage digital radiographs (KVDRs) by Varian Trilogy machine-borne OBI KV image verification system. The KVDRs images were matched with the DRR images reconstructed by the planned system to obtain the setup errors in the left and right, head and foot, and ventral and back directions between two groups. Each patient was verified for 10 times to obtain 400 sets of data. The independent sample t-test was adopted to analyze the setup errors between two groups. The external expansion value of graded setup errors from clinical target volume (CTV) and planned target volume (PTV) was calculated. Results: The setup errors in the left and right, head and foot, ventral and back directions between the styrofoam fixation and vacuum pad groups were (1.63±1.29) mm and (1.83 ±1.61) mm (P=0.18), (1.46±1.51) mm and (2.26±2.03) mm (P=0.00), and (1.30±1.35) mm and (1.91±1.67) mm (P=0.00), respectively. The external expansion values of setup errors from CTV to PTV were 2.19 mm, 2.51 mm, 1.57 mm and 2.40 mm, 3.97 mm and 2.63 mm, respectively. Conclusion Both two fixation methods meet the clinical requirements. However, the setup accuracy and reproducibility in the polyurethane styrofoam group are better than those in the vacuum negative pressure pad group.

Objective To probe into the effect of sitagliptin on blood glucose fluctuation of the patients with type 2 diabetes mellitus(T2DM) and poor control by insulin aspart 30.Methods Ninety cases of T2DM and poor control by insulin aspart 30 in affiliated Zhongshan hospital from January 1,2014 to December 31,2014 were selected and randomly divided into three groups:simply continuous subcutaneous insulin injection(CSII),acarbose combined CSII group(CSII + Aca) and sitagliptincombined CSII group (CSII + Sig),30 cases in each group.Three groups received the intensive treatment for 2 weeks,and72-h continuous glucose monitoring was performed on last 3 d.The 24 h mean blood glucose(24 hMBG),largest amplitude of glycemic fluctuation(LAGE),mean amplitude of glycemic excursion(MAGE) within 1 d,postprandial blood glucose spike(PGS),postprandial glucose peak time(△t),postprandial glucose excursion(PPGE) and total T were observed within 24 h.The difference of insulin dose(△ insulin),hypoglycemia incidence,glucose-target rate,blood glucose profiles were compared at the end of treatment.Results After two-week treatment,intraday blood glucose variation indicators(24 hMBG,LAGE and MAGE) and postprandial blood glucose variation indicators (PGS,△t,PPGE and total T) in the CSII+Sig and CSII+-Aca groups were significantly lower than those in the CSII group(P＜ 0.05),while the differences in blood glucose variation indicators between the CSII+Sig group and CSII+-Aca group were not statistical significant(P＞ 0.05).In the comparison after treatment,△ insulin,hypoglycemia incidence and glucose-target rate in the CSI + Sig group were lower(P＜0.05).Conclusion The combined application of short-term CSII and sitagliptin will achieve a better effect than the combination with acarbose,can smoothly and steadily reduces the blood glucose level,relieves the whole day glucose fluctuations,effectively reduces △ insulin,and has lower hypoglycemia occurrence rate.

Guangdong province assumes the task of pilot exploration and demonstration for building the preventive health service system of Chinese medicine. In the pilot process of preventive treatment of disease, a health pro-ject of Chinese medicine, sectoral agreements and policy studies are focusing issues. This paper explores the pre-ventive health service system building of Chinese medicine in G uangdong province , from following aspects such as access policy of service agencies, access policy of professional service staff, evaluation mechanism and verify sys-tem, the revision of existing medical subjects of medical institutions, health insurance policies and compensation policies, price policies, proactive technology policies and fiscal policies, incentive policies for the introduction of private capital .

Objective To analyze and summarize the efficacy and the experience in the application of type Ⅰ and type Ⅱ bundled pancreaticojejunostomy in pancreaticoduodenectomy. Methods Between Jan.2005 and Dec. 2009, a total of 38 patients who underwent bundled pancreaticojejunostomy was enrolled, and their clinical data were retrospectively analyzed. 20 patients received type Ⅰ bundled pancreaticojejunostomy and 18 patients received type Ⅱ bundled pancreaticojejunostomy. The operative time, postoperative hospital stay, mortality and complications were compared. Results The operative time of type Ⅰ bundled pancreaticojejunostomy was (91 ± 20) min, and it was (63 ± 21) min in type Ⅱ procedure, and the difference was statistically significant (P ＜ 0. 05). The mortality and complications, postoperative hospital stay were 10.0%(2/20), 45.0% (9/20) and (20 ±2)d in type Ⅰ procedure, while they were 5.6% (1/18),38.9% (7/18) and(23 ±2)d in type Ⅱ procedure, and the difference was not statistically significant.Conclusions There was no significant difference in the effects between type Ⅰ and type Ⅱ bundled pancreaticojejunostomy. Carefully selective application of type Ⅰ and type Ⅱ bundled pancreaticojejunostomy helps complete these procedures.