Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Objective To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis.Methods The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network,Wipu,Wanfang,The Cochrane Li-brary,Web of science and Pubmed,and statistical analysis was performed using RevMan 5.3 software.The rates of malrotation,rotational deformity,internal/external deformity,anterior/posterior deformity,non-union,infection,secondary surgery and op-erative time were compared between the fibula fixation and non-fixation groups.Results A total of 11 publications were includ-ed,six randomised controlled trials and five case-control trials,eight of which were of high quality.A total of 813 cases were in-cluded,of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22,95％CI(0.10,0.45),P＜0.000 1]and internal/external deformity[RR=0.34,95％CI(0.14,0.84),P=0.02]and promoted fracture heal-ing[RR=0.76,95％CI(0.58,0.99),P=0.04].In contrast,the rates of poor reduction[RR=0.48,95％CI(0.10,2.33),P=0.36],anterior/posterior deformity[RR=1.50,95％CI(0.76,2.96),P=0.24],infection[RR=1.43,95％CI(0.76,2.72),P=0.27],sec-ondary surgery[RR=1.32,95％CI(0.82,2.11),P=0.25],and operative time[MD=10.21,95％CI(-17.79,38.21),P=0.47]were not statistically significant(P＞0.05)for comparison.Conclusion Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.

Objective:To study the clinical safety and validity of retrograde new endoscopic field of vision in miniature pigs.Methods:6 live miniature pigs were selected as study subjects,En-doscopic Retrograde New View(ERNV)was selected.The performance,image quality and intraoper-ative and postoperative complications were evaluated.To evaluate whether all the experimental ani-mals could complete the relevant endoscopy.Verify ERNV's operating performance,including whether the duodenoscope can enter the biliary tract smoothly,and made sure whether the injection,suction,and instrument channels were unobstructed.Choledochoscope image clarity,color resolu-tion,image deformation and distortion,accurate evaluation of lumen conditions and clear observation of mucosal surface conditions were analyzed.Whether there were operant injuries such as bleeding and perforation,as well as adverse events such as respiratory depression and cardiac arrest.The sur-vival status and adverse reactions of all pigs were observed.Results:The choledochoscope was successfully inserted into the bile duct of 6 miniature pigs.The product had good operation perfor-mance and could enter the bile duct through the duodenoscope smoothly.The injection,suction and instrument channels were relatively smooth.In addition,the endoscopic images are clear,with better color resolution,and without image deformation and distortion,which can realize accurate evaluation of the conditions in the lumen and observe the mucosal surface conditions more clearly.No bile duct stenosis or dilatation occurred in all miniature pigs,and the bile duct mucosa was smooth,without hyperemia and edema,and no abnormal thickening or bending of mucous vessels.During the exami-nation,there were no operational injuries such as bleeding and perforation,and no adverse events such as respiratory depression and cardiac arrest occurred.The vital signs of all miniature pigs tended to be stable after operation,and the survival state was good,and there were no complications such as cholangitis,bleeding and perforation.Conclusion:ERNV has good clinical safety and efficacy,ex-cellent operation performance and excellent image quality,and is worthy of clinical application.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Photothermal therapy is a new type of tumor therapy that uses near-infrared laser to specifically activate the photothermal agent accumulated in the lesion site, so as to achieve thermal ablation of cancer cells. However, the long metabolic cycle and difficult clearance of photothermal agent materials in vivo are also one of the major obstacles hindering their clinical transformation. In this work, we used hemoglobin as a novel stabilizer, hexachloroplatinic acid as a novel oxidant, and pyrrole as a monomer to prepare hemoglobin-stabilized platinum-based polypyrrole nanoparticles (Hb@PtP) by a one-step oxidative polymerization method and investigated in detail to study their physicochemical properties, such as morphology and structure. After polyethylene glycol modification, the particle size of obtained Hb@PtPP was 99.08 ± 8.3 nm and the zeta potential was -18.7 ± 1.2 mV. Transmission electron microscopy showed that the Hb@PtPP nanoparticles exhibited irregular spherical shape and uniform dispersion in the system. Under the irradiation of 808 nm laser with different power densities, Hb@PtPP showed power density-dependent temperature-raising behavior, and CCK-8 and dead-live staining experiments confirmed that they could effectively exert the photothermal effect to kill tumor cells. Small living animal imaging results demonstrated that Hb@PtPP had good tumor targeting and retention ability, and achieved tumor growth inhibition and ablation in vivo under laser excitation. All animal experiments involved in the study were performed in accordance with the program approved by the Animal Care and Use Committee of the Chinese Academy of Medical Sciences, Beijing Union Medical College, Institute of Radiation Medicine [IRM/2-IACUC-2312-005].

Microsporidia is a group of intracellular parasitic eukaryotic microorganisms that pose threats to livestock fish production and human health, but there is no special chemo-therapeutic drug available for the treatment of microsporidia currently. In this study, sulfonamide derivatives of spectinomycin were designed by taking into consideration the low toxicity of spectinomycin and the favorable pharmaceutical properties of sulfonamides. Through the exploration of reaction conditions, a total of 21 target molecules were synthesized with a yield of 52%-74% and their chemical structures were confirmed by ¹H NMR, ¹³C NMR, and high resolution mass spectrometry (HR MS). By screening in vitro, the host cell cytotoxicity and biological activity of target molecules to Encephalitozoon hellem, a representative of vertebrates infecting microsporidia, were studied. It was found that four target molecules each could inhibit or promote the proliferation of E. hellem. In this study, the synthesis method of sulfonamide derivatives of spectinomycin was established, and new compounds effective against E. hellem were discovered, which provided a new idea for the further derivatization of spectinomycin and the development of therapeutic drugs targeting microsporidia.

Photodynamic therapy is an emerging cancer therapy with clinical prospects, which plays a specific role in the tumor site and causes less harm to the human body. However, the toxicity of small molecules of hydrophobic photosensitizer, the tumor hypoxia microenvironment, and the biodegradability of nano-carrier systems affect its antitumor efficacy and metabolic clearance in vivo. In this paper, hexachloroplatinic acid was used as a novel oxidizing agent to initiate oxidative polymerization of pyrrole/amino pyrrole to achieve the amino functionalization; further reduced platinum acid anion in the nanostructures into platinum nanoclusters by sodium borohydride as a reducing agent to fabricate platinum nanocluster-doped polypyrrole nanoparticles (PtPPy); and finally, this functional nanoparticles delivering meso-tetra (4-carboxyphenyl) porphine (TCPP) were obtained by amide-bonded coupling of photosensitizers TCPP drug (PtPPy@T). The nanomedicine had a spherical structure, uniform morphology, a particle size of 91.93 ± 13.45 nm, and a zeta potential of -18.39 ± 1.4 mV. Experiments demonstrated that PtPPy@T could react with hydrogen peroxide overexpressed in the tumor to generate a large amount of oxygen, which could relieve the tumor hypoxia microenvironment, and at the same time, provided a sufficient substrate for the subsequent PDT; using 658 nm laser irradiation, the photodynamic effect of PtPPy@T was activated, which catalyzed the conversion of oxygen to singlet oxygen, thus triggering oxidative damage and inducing apoptosis in tumor cells; experimental studies showed that the PtPPy@T nanomedicine had a better tumor inhibitory effect in vivo and in vitro. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Radiological Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College (IRM/2-IACUC-2312-006).

In view of the problem of slow development of intensive care medicine in Xizang, the research team made full use of the national partner assistance to Xizang, gathered resources across all cities in Xizang, and formed a national academic platform for critical care medicine in plateau areas. Adhering to the academic orientation with hemodynamics as the main topic, critical care ultrasound as the bedside dynamic monitoring and evaluation method, and blood flow-oxygen flow resuscitation as the core connotation, we have achieved the goals of improving the critical care talent echelon throughout Xizang, driving the overall progress of intensive care medicine in Xizang, making a figure in China, and focusing on training of top-notch talents.

In black tea,theaflavins (TFs) are one important class of substances that determine sensory quality and have significant medicinal activities. In addition to the four kinds of common TFs,there may be many other theaflavin analogues (TFAs) with similar chemical structures in tea,but the study on them is very limited. Based on the characteristic sub-structure,mass spectrometry (MS) and MS/MS information,a method for screening and annotation of TFAs from the complex ultra high performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) data was proposed in this work. By analyzing the oxidation and polymerization process of a few TFs,the theoretical reaction model of TFs were summarized,which was used to calculate the precursor ion values of potential TFAs. Meanwhile,the diagnostic fragmentation ions and neutral loss of TFAs according to the fragmentation pathways obtained from chemical standards or documented in literatures were summarized. As a result,36 kinds of compounds were successfully annotated based on the calculated precursor ion values and the MS fragmentation patterns,among which 6 kinds of compounds were reported for the first time in tea. In vitro synthesis experiments were carried out to verified the annotation results. Based on the results of quantitation of 36 kinds of TFAs,a partial least squares-discriminant analysis model was used to investigate the changes of these components during black tea manufacturing. The results indicated that these novel TFAs could be used to effectively distinguish the black tea samples before and after fermentation.