Objective To provide strategies and suggestions for the development of clinical research in children's spe-cialized hospitals.Methods With a Class A tertiary children's specialty hospital in Shanghai as an example,the SWOT model is used to analyze the strengths,weaknesses,opportunities,and threats of clinical research development in the hospital,and to propose corresponding strategies and suggestions.Results The hospital has distinguished disciplinary advantages,tremendous strength in scientific research,a strong team of talents,and steady progress in the construction of clinical research center.The weaknesses include imperfect clinical research management system,imperfect informatization construction,and insufficient allo-cation of full-time management personnel.There are now opportunities of high policy support,increasing funding support,the shift in clinical demand,and good prospects for development of investigator-initiated trials(IIT).The hospital is also faced with the threat of difficulty in conducting pediatric clinical research and fierce competition among similar hospitals.Conclusion We could promote the development of pediatric clinical research by incentivizing the conduction of clinical research,strengthening the construction of clinical research system,improving the clinical research capabilities,and building a collaborative network for ped-iatric multicenter clinical research.

Objective:To optimize the alcohol precipitation process of Quhan Zhufeng Granules.Methods:Taking the volume fraction of ethanol, the relative density of the concentrated solution and the standing time as the investigation factors, the Z value of the total evaluation of gentiopicrin content, oleanolic acid content and dry paste yield of gentiana macrophylla as the evaluation indexes, the star-point design-response surface method was used to optimize the alcohol precipitation process.Results:The optimal the alcohol precipitation process of Quhan Zhufeng Granules: concentration relative density 1.08 g/ml (90-95 ℃), alcohol precipitation at the end of volume fraction of 62% ethanol, standing for 16 h.Conclusion:The alcohol precipitation process using overall desirability and central composite design is stable and feasible, and has good predictability, which can provide experimental basis for further scale production.

Objective The purpose of this article is to summarize and review the current status of the construction of clinical research evaluation systems in domestic public hospitals,identify existing problems in the evaluation system,and propose development strategies and suggestions.Methods Retrieved relevant articles,dissertations and policies from the past five years(2018-2022),screened the titles,viewed the full texts of 52 selected papers and their references,and summarized them.Results The"five-only"indicators have long been an important indicator for evaluating clinical research in public hospitals,but in today's scientific research environment and policy environment,the"five-only"evaluation system has revealed its utilitarian draw-backs and gradually evolved into a hindrance to scientific research.It is urgent to break through the"five-only"orientation and establish a clinical research evaluation system oriented towards"transforming and applying transformation of scientific research achievements".Conclusion The evaluation system for clinical research should break the previous"five-only"evaluation model based on quantity-oriented scientific research evaluation.We can draw on the framework of the research output,influence,and environment indicators in the UK's REF Excellence Framework model,combine the American APT system and the Chinese STEM indicator dimensions,explore multi-outcome evaluation,integrate developmental indicators,and continuously improve the indica-tor system and application methods in practice to promote the development of clinical research in public hospitals.

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

Objective:To explore the value of diffusion tensor imaging (DTI) in evaluating the effects of hyperbaric oxygen therapy (HOT) in treating spinal cord injury.Methods:The modified Allen′s method was used to induce a traumatic spinal cord injury in 30 rats who were then divided randomly into an injured group and a treatment group, each of 15. The treatment group was given HOT twice a day for 3 days, then once a day for a total of 4 weeks. The injured group did not receive HOT. DTI was performed (along with Basso-Beattie-Bresnahan (BBB) evaluation) at 0h, 6h, 24h, as well as 3, 7, 14, 21 and 28 days after the operation. Two-factor repeated measures ANOVA was conducted to analyze any differences in the DTI results: the fractional anisotropy, mean apparent diffusivity, radial diffusivity and axial diffusivity, as well as the BBB scores. LSD t-tests were performed to analyze the significance of the differences at different time points.Results:At each time point after 24h the average FA value of the treatment group was significantly higher than the injured group′s average, while its average MD and RD values were significantly lower. Beyond 14 days the average AD value of the treatment group was significantly higher than that of the injured group. The treatment group′s average BBB score was also significantly higher at all the time points beyond 3 days.Conclusions:DTI results can evaluate spinal cord function and provide valuable information for the dynamic assessment of hyperbaric oxygen therapy after a traumatic spinal cord injury, and the therapy promotes the recovery of motor function, at least in rats.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe diseases. This study aimed to validate the predictive ability of risk models in patients with SJS/TEN and propose possible refinement in China. Patients in the Department of Dermatology of Huashan Hospital from January 2008 to January 2019 were included. Results showed that the severity-of-illness score for TEN (SCORTEN) had a good discrimination (area under the receiver operating characteristic curve (AUC), 0.78), and it was superior to auxiliary score (AS) and ABCD-10, which indicates age, bicarbonate level, cancer, dialysis, and 10% involved body surface area (AUC, 0.69 and 0.68, respectively). The calibration of SCORTEN (Hosmer-Lemeshow goodness-of-fit test, P = 0.69) was also better than that of AS (P = 0.25) and ABCD-10 (P = 0.55). SCORTEN and ABCD-10 were similar (Brier score (BS), 0.04 and 0.04) in terms of accuracy of predictions. In addition, the imaging appearance of pulmonary consolidation on computed tomography was associated with high mortality. Refined models were formed using the variables and this imaging appearance. The refined AS and ABCD-10 models were similar in discrimination compared with the original SCORTEN (0.74 vs. 0.78, P = 0.23; 0.74 vs. 0.78, P = 0.30, respectively). Therefore, SCORTEN showed good discrimination performance, calibration, and accuracy, and refined AS or ABCD-10 model may be an option when SCORTEN variables are not available.
Cohort Studies ; Humans ; Retrospective Studies ; Severity of Illness Index ; Stevens-Johnson Syndrome/diagnostic imaging* ; Tomography

Objective: The purpose of our study was to investigate the predictive abilities of clinical and computed tomography (CT)features for outcome prediction in patients with coronavirus disease (COVID-19). Materials and Methods: The clinical and CT data of 238 patients with laboratory-confirmed COVID-19 in our two hospitalswere retrospectively analyzed. One hundred sixty-six patients (103 males; age 43.8 ± 12.3 years) were allocated in thetraining cohort and 72 patients (38 males; age 45.1 ± 15.8 years) from another independent hospital were assigned in thevalidation cohort. The primary composite endpoint was admission to an intensive care unit, use of mechanical ventilation, ordeath. Univariate and multivariate Cox proportional hazard analyses were performed to identify independent predictors. Anomogram was constructed based on the combination of clinical and CT features, and its prognostic performance wasexternally tested in the validation group. The predictive value of the combined model was compared with models built on theclinical and radiological attributes alone. Results: Overall, 35 infected patients (21.1%) in the training cohort and 10 patients (13.9%) in the validation cohortexperienced adverse outcomes. Underlying comorbidity (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.67–6.71;p < 0.001), lymphocyte count (HR, 0.12; 95% CI, 0.04–0.38; p < 0.001) and crazy-paving sign (HR, 2.15; 95% CI, 1.03–4.48;p = 0.042) were the independent factors. The nomogram displayed a concordance index (C-index) of 0.82 (95% CI, 0.76–0.88),and its prognostic value was confirmed in the validation cohort with a C-index of 0.89 (95% CI, 0.82–0.96). The combinedmodel provided the best performance over the clinical or radiological model (p < 0.050). Conclusion Underlying comorbidity, lymphocyte count and crazy-paving sign were independent predictors of adverseoutcomes. The prognostic nomogram based on the combination of clinical and CT features could be a useful tool for predictingadverse outcomes of patients with COVID-19.

Objective To explore the value of DTI quantitative parameters in evaluating neurological function changes of acute traumatic spinal cord injury (TSCI)in rat models.Methods The modified Allen's dropping weight technique was used to establish TSCI rat models.Then the rats were divided into mild injury group,moderate injury group and severe injury group (each n=10).DTI examination and Basso-Beattie-Bresnahan (BBB) score were performed pre-TSCI and 0 h,6 h,24 h,3 day,7 day and 14 day post-TSCI,respectively.The BBB scores and DTI parameters,including FA,mean apparent diffusivity (MD),radial diffusivity (RD) and axial diffusivity (AD) were measured and compared among groups.The correlation between BBB scores and the parameters was evaluated.Results The differences of FA,MD and RD value were statistically significant among varying injury degree groups and different time points after TSCI (all P＜0.05).AD value had statistical difference among different time points (F=12.720,P＜0.001),whereas no difference was found among varying injury degree groups (F=0.469,P=0.630).FA and MD values decreased while RD increased 0 h post-TSCI.Then RD and MD increased continuously,whereas FA decreased continuously until 24 h post TSCI (all P＜0.05),and the parameters kept stable after 24 h post-TSCI (all P＞ 0.05).The BBB scores were lowest on 0 h post-TSCI,then maintained increasing (all P＜0.05).In addition,the BBB scores and MD values had good correlation (r=0.958,P＜ 0.01).Conclusion DTI can quantitatively evaluate function changes of TSCI in rat models.Moreover,treatment within 24 h post-TSCI might be recommended for TSCI therapy.

Purpose To explore the value of 320 row dynamic volume CT angiography in the preoperative assessment of juvenile nasopharyngeal angiofibroma (JNA) and in determining feeding arteries.Materials and Methods The imaging data of 18 cases with JNA proved by surgery and pathology and examined by 320 row dynamic volume CT were analyzed retrospectively.The imaging staging and feeding artery of tumors were determined.Results Most tumors (17/18) showed heterogeneous enhancement in the early stage of enhancement.With the extension of time,the enhancement scope of lesions expended.The time-density curve (TDC) of 11 cases demonstrated rapid ascending and rapid descending after injecting contrast,while 7 cases showed continuous increasing.The blood supply of all tumors included the external carotid artery system of the affected side and showed a close relationship with tumor staging.With the increase of tumor stage,the number of feeding arteries increased (r=0.858,P＜0.05).The feeding arteries of stage Ⅱc and stage Ⅲ tumors included ipsilateral maxillary artery and ascending pharyngeal artery.Besides,the effective radiation dose of 320 row CT angiography for searching arteries [(3.30±0.08) mSv]was less than that of DSA [(7.62±2.39) mSv] (t=-7.98,P＜0.05).Conclusion The 320 row dynamic volume CT imaging of JNA has certain characteristics,which can display the blood supply artery and accurate staging of tumors,thus it has important value in preoperative evaluation of JNA.

BACKGROUNDThe occurrence of contrast induced acute kidney injury (CIAKI) has a pronounced impact on morbidity and mortality. The aim of the present study was to appraise the diagnostic efficacy of age, estimated glomerular filtration rate (eGFR) and ejection fraction (AGEF) score (age/EF(%)+1 (if eGFR was <60 ml × min(-1)× 1.73 m(-2))) as an predictor of CIAKI in patients with diabetes mellitus (DM) and concomitant chronic kidney disease (CKD).

METHODSThe AGEF score was calculated for 2 998 patients with type 2 DM and concomitant CKD who had undergone coronary/peripheral arterial angiography. CIAKI was defined as an increase in sCr concentration of 0.5 mg/dl (44.2 mmol/L) or 25% above baseline at 72 hours after exposure to the contrast medium. Post hoc analysis was performed by stratifying the rate of CIAKI according to AGEF score tertiles. The diagnostic efficacy of the AGEF score for predicting CIAKI was evaluated with receiver operating characteristic (ROC) analysis.

RESULTSThe AGEF score ranged from 0.49 to 3.09. The AGEF score tertiles were defined as follows: AGEFlow ≤ 0.92 (n = 1 006); 0.92 1.16 (n = 992). The incidence of CIAKI was significantly different in patients with low, middle and high AGEF scores (AGEFlow = 1.1%, AGEFmid = 2.3% and AGEFhigh = 5.8%, P < 0.001). By multivariate analysis, AGEF score was an independent predictor of CIAKI (odds ratio = 4.96, 95% CI: 2.32-10.58, P < 0.01). ROC analysis showed that the area under the curve was 0.70 (95% CI: 0.648-0.753, P < 0.001).

CONCLUSIONThe AGEF score is effective for stratifying risk of CIAKI in patients with DM and CKD undergoing coronary/peripheral arterial angiography. (Clinical Trial identifier: NCT00786136).

Acute Kidney Injury ; physiopathology ; Contrast Media ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Renal Insufficiency, Chronic ; physiopathology