Background Dynamic observation in morphology and histology of conjunctival filtering bleb in rats can contribute to form ideal filtering blebs by interferencing the process of scarring.Objective This study was designed to observe the survival time,morphological and histopathological changes of conjunctival filtering bleb after filtering surgery.Methods Filtering surgeries were performed on 60 male adult Sprague-Dawley rats by implanting drainage tubes into the anterior chamber.The shape of filtering blebs was examined by slit lamp microscope 1 day,3,5,7,14,28 days after surgery.The filtering was typed according to the criteria of Kronfeld.Areas of the filtering bleb were measured and compared at various time points after surgery.Conjunctival and subconjunctival tissues at filtering zone were obtained 1 day,3,5,7,14,28 days after surgery,respectively,and hematoxylin and eosin staining was used for the histopathological evaluation.Results Well-elevated filtering blebs formed on the first day after surgery in 60 rat eyes.The survival time of filtering bleb was 7-17 days with the mean time of (11.93±2.23) days.Survival rate of the filtering blebs was 100％ in 1-5 days,77％ in 7 days,20％ in 14 days and 0 in 28 days after operation.The filtering blebs were functional (Ⅰ type) in 1-5 days after operation,23 eyes were functional in 7 days after operation (13 eyes were Ⅰ type,10 eyes were Ⅱ type),4 eyes were functional in 14 days after operation (2 eyes were Ⅰ type,2 eyes wereⅡtype).The filtering area shrunken from (7.50±1.08) mm2 to (1.83±0.35) mm2during the observational duration.The filtering blebs area of different days after surgery were statistically significant (F =180.056,P=0.000),and significant differences were found between any two timepionts after surgery (all at P =0.000).Histological examination showed that inflammatory finding was dominant in postoperative day 1-3,such as infiltration of inflammatory cells,vasodilatation and edema of tissue.However,proliferating manifestation became the main signs 5 days later,showing the increase of fibroblasts,neovascularization and collagen formation.Conclusions The model of conjunctival filtering blebs in rats can be successfully established by implanting silicone tube into anterior chamber.The inflammatory response,proliferation of fibroblasts and the accumulation of collagen fibers are involved in the scarring process of filtering blebs.

Objective The purpose of this study was to compare the image quality of readout-segmented EPI (RS-EPI) and that of standard single-shot echo-planar imaging (SS-EPI) in patients with scrotal diseases. Methods Initial diagnosis of scrotal diseases were included in the prospective study, all patients underwent scrotum routine MRI and RS-EPI, SS-EPI sequence at 3.0 T. A total of 38 patients were recruited qualitative assessment ,and 29 patients proved by operation and pathology (malignant 21 cases and benign 8 cases) were included quantitative analysis.For qualitative comparison of image quality, two readers independently assessed the two sets of DWI, which consisted of identification of structure and geometric distortion of scrotum (epididymis,testes, lesion) using a 5-point Likert scale. For assessment of image parameters, signal-to-noise ratio (SNR), contrast, contrast-to-noise ratio (CNR),apparent diffusion coefficient value of normal testis and testis distortion ratio of anatomical(T2WI)/DWI fusion image were calculated. Inter-observer agreement was assessed with the Kappa statistics, the differences of scores of
RS-EPI and SS-EPI were compared by using Wilcoxon rank-sum test, and image parameters were compared by using paired sample t test. Results There was good reader agreement in the scores, the Kappa value were 0.77, 0.74, 0.80, 0.87. The difference of identification of structure and geometric distortion on RS-EPI and SS-EPI had statistic significance, the RS-EPI was superior to SS-EPI in image quality (all P<0.05).The SNR, contrast of benign lesion for two sequences had no statistic significance(P values were 0.352, 0.124, respectively), but the difference of CNR had statistic significance(P<0.05). The SNR,contrast and CNR of malignant lesion for two sequences had statistic significance (all P<0.05). The mean size of the testis was (35.61 ± 9.78)mm, the mean distance in fusion image of RS-EPI or SS-EPI with T2WI were (3.80 ± 1.32)mm and (7.54 ± 2.62)mm, and the mean distortion ratios of the two set were (11.1 ± 0.6)% and (22.4 ± 19.2)%, respectively, the difference of two sets had statistic significance(P<0.05). There was no significant difference in the ADC obtained by using either DWI method(t=0.396,P=0.796), the mean ADC values of normal testes for RS-EPI and SS-EPI, respectively, were (1.18 ± 0.06) × 10-3mm2/s, (1.24 ± 0.11) × 10-3mm2/s.Conclusion RS-EPI DWI images is a feasible technique in the scrotum for producing high-resolution DWI with reduced geometric distortion and offers potentially superior image quality compared to SS-EPI at 3.0 T.

Objective:To observe the 95% effective dose (ED95) of Propofol mono-sedation for successfully inserting the gastroscope in healthy adults by biased coin design up-and-down sequential method.Methods:Using prospective study method, a total of 40 patients proposed for painless gastroscopy in Beijing Friendship Hospital, Capital Medical University from April to May 2021 were selected. There were 15 males and 25 females. American Society of Anesthesiologists (ASA) classification: grade I 26 cases, grade Ⅱ 14 cases. The mean age was (50.80±9.14) years, and the mean body mass index was (24.08±2.65) kg/m 2. Propofol mono-sedation was used in all patients. The initial dose of Propofol was set as 1.6 mg/kg, adjusted with 0.1 mg/kg as a step size. The biased coin design up-and-down sequential method was used in this study. The Propofol dose of subsequent patients was determined by the response to gastroscope insertion of the previous patient. If the gastroscopy insertion reaction of the previous patient was positive, the Propofol dose of the next patient was increased by one level (0.1 mg/kg); if the gastroscopy insertion reaction of the previous patient was negative, the biased coin random was performed, and the Propofol dose used by the next patient was reduced by one level (0.1 mg/kg) with 5% probability and remained unchanged with 95% probability. Changes of mean arterial pressure, heart rate and pulse oxygen saturation were recorded at different time points, and adverse reactions such as perioperative hypotension, bradycardia, tachycardia and hypoxemia were recorded. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between different time points. The ED95 and 95% CI of Propofol in inhibiting the response to gastroscope insertion was calculated by Probit regression analysis. Results:All 40 patients successfully completed the gastroscopy. The calculated ED95 of Propofol mono-sedation for successfully inserting the gastroscope was 2.58 mg/kg with 95% CI of 2.40-3.31 mg/kg. The mean arterial pressure before anesthesia, after propofol injection, at the time of gastroscopy going through throat and immediately after examination was (97.33±13.34) mmHg, (93.15±11.35) mmHg, (78.95±9.30) mmHg, (79.38±9.94) mmHg (1 mmHg=0.133 kPa), respectively. The mean arterial pressure at the time of gastroscopy going through throat and immediately after examination decreased significantly, the difference was statistically significant ( P<0.01). There were no significant differences in heart rate and pulse oxygen saturation compared with those before anesthesia ( P>0.05). Conclusion:The ED95 of Propofol mono-sedation for successfully inserting the gastroscope is determined as 2.58 mg/kg (95% CI: 2.40-3.31 mg/kg) by biased coin design up-and-down sequential method.

Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins