Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

Objective:To evaluate endoscopic retrograde appendicitis therapy in treatment of children with acute uncomplicated appendicitis.Methods:Sixty children patients were admitted at the Affiliated Hospital of Zhengzhou University from Oct 2019 to Jun 2021 and were divided into ERAT group ( n=30) and LA group ( n=30). Results:All operations were successfully performed . ERAT children started oral feeding earlier [(6.8±2.0) h vs. (12.3±2.0) h, t=-10.636, P<0.001], postoperative hospital stay was shorter [(3.2±1.3) d vs. (5.0±1.3) d, t=-5.360, P<0.001]. After 14 months follow up, the recurrence rate in the ERAT group was 6%. The complication rate of LA was 10%. Conclusion:ERAT is a safe and effective therapy in treating children with acute uncomplicated appendicitis with low,acceptable recurrence rate.

Objective:To investigate the contrast-enhanced ultrasound (CEUS) features of inflammatory hepatocellular adenoma (I-HCA).Methods:The contrast-enhanced ultrasound features I-HCA of 28 cases from April 2009 to November 2019 in Zhongshan Hospital, Fudan University were retrospectively analyzed, including arterial phase enhancement pattern, the homogeneity of enhancement, subcapsular enhancement, and the internal perfusion defect. All I-HCA lesions were divided into >5 cm group( n=9) and ≤5 cm group( n=19), the CEUS features between the two groups were compared. Results:All I-HCA lesions were hyper-enhanced in the arterial phase, among which 39.3% (11/28) showed diffuse filling, 39.3%(11/28) showed centripetal filling, and 21.4%(6/28) showed centrifugal filling pattern. Twenty-five percent (7/28) of I-HCAs showed heterogeneous enhancement, 10.7% (3/28) revealed unenhanced areas within the lesions. Subcapsular vessels were observed in 67.7 (21/31) of I-HCA lesions. Heterogeneous enhancement and unenhanced areas were more frequently detected in lesions >5 cm ( P=0.020, 0.026, respectively), while there was no difference in the enhancement pattern and subcapsular vessels between the two groups ( P>0.05). Inportal venous phase, 42.9%(12/28) of I-HCAs showed hypo-enhancement, and 57.1%(16/28) of lesions showed washout in late phase. According to "hyper-enhancement in arterial phase, sustained hyper- or iso-enhancement in portal venous and late phase" by CEUS, the diagnostic accuracy of benign lesion was 42.9%(12/28). According to any of hyper-enhancement pattern in arterial phase, subcapsular vascular enhancement, and sustained hyper- or iso-enhancement in portal venous and late phase, the diagnostic accuracy of I-HCA was 71.4% (20/28). Conclusions:CEUS is valuable in the diagnosis of inflammatory hepatocellular adenoma.

Objective: To investigate the current basic situation of the staff of ultrasound departments in Shanghai′s medical institutions, for providing references in making management policy of these professionals. Methods: Questionnaire surveys on human resource and service ability were made to all the ultrasound departments of medical institutions in Shanghai in December 2013 and November 2018 respectively. Data of the two surveys were compared and analyzed, and were descriptively analyzed by mean and percentage. Results: The number of ultrasound professionals per 10 000 people in Shanghai was 1.04 in 2018. Tertiary hospitals had advantages in the number of the professionals, and the proportion of professional qualification, age, education background and professional title of the professionals. Compared to those data in 2013, the number of ultrasound professionals had increased 31.8% in 2018. The proportion of medical practitioners with medical imaging specialty was 95.6%(2 063/2 158), and had increased by 4.7 percent. The medical services workload of ultrasound was 19.82 million person-time, and had increased 45.8%. Conclusions Development of ultrasound departments was rapid, but the development of professionals was unbalanced with the development of medical services. It is suggested to strengthen training of ultrasound professionals and improve the system of hierarchical medical system.

Objective: To investigate the current basic situation of ultrasound machines of ultrasound departments in Shanghai medical institutions, and to provide the basis for making management policy in order to promote medical quality. Methods: Questionnaire surveys about ultrasound machines and service ability including producing countries of ultrasound machines, the number of ultrasound machines, using years of ultrasound machines, yearly workload and the yearly number of patients that each ultrasound machine accepted were made in 2013 and 2018, respectively. Statistical results were compared between the two surveys. Results: Compared with 2013, the share of imported ultrasound machines declined in 2018 (82% vs 91%). Compared with 2013, the number of ultrasound machines in Shanghai medical institutions had increased by 31% in 2018 (2 123 vs 1 617). The occupancy rate of ultrasound machines in tertiary hospitals was the highest (tertiary hospitals 40%, secondary hospitals 25%, primary grade hospitals 20%, and private hospitals 15%). Compared with 2013, the proportion of ultrasound machines that have been used for more than 10 years increased (9% vs 4%), the yearly workload of ultrasound examination had increased by 46% (19.82 million person-time vs 13.59 million person-time). Tertiary hospitals bored the highest proportion of the workload (tertiary hospitals 51%, secondary hospitals 35%, primary grade hospitals 4%, and private hospitals 10%). Currently, the number of ultrasound machines per 10, 000 people in Shanghai was 1.14. The yearly number of patients that each ultrasound machine accepted had increased by 11% (9300 person-time vs 8400 person-time in 2018). Conclusions The scale of ultrasound departments in Shanghai medical institutions has been developing. Brand localization of ultrasound machines is improving. However, the renewal ability of ultrasound machines still needs to be improved. The workload of ultrasound department is getting heavier. Hierarchical diagnosis and treatment is unbalanced.

Objective? To design a Seminar curriculum model for graduate nursing students based on the discussion of SCI papers and evaluate its effect on students' scientific research ability. Methods? Using the cluster sampling method, 57 graduate nursing students from a medical university were selected as the control group, and 58 graduate nursing students were selected as the experimental group. Using SCI nursing papers as the subject of discussion, the control group implemented the empirical Seminar curriculum model. The experimental group constructed and implemented the curriculum model based on the research capability structure model and the Seminar learning objectives. The effects of the intervention were evaluated using the Research Motivation Scale (RMS), the Nursing Research Self-Efficacy Scale (NURSES), the Nursing Staff Scientific Research Self-Assessment Scale (SRASES), and the Seminar Survey Questionnaire. Results? After the course, the scores of RMS total score, intrinsic motivation and extrinsic motivation of the nursing students in the experimental group were higher than those in the control group, and the differences were statistically significant (P＜0.05). At the end of the course, the scores of the NURSES total scores, scientific knowledge resources of the nursing students and "effect of collective research" in the experimental group were higher than those in the control group, and the differences were statistically significant (P＜0.05). At the end of the course, the scores of the total scores and dimensions of the SRASES in the experimental group were higher than those in the control group, and the differences were statistically significant (P＜0.05). Conclusions? The Seminar curriculum model based on SCI papers can improve the motivation, scientific research efficacy and scientific research ability of graduate nursing students to a certain extent. However, it is still necessary to further explore the curriculum model to help students avoid the motivation of scientific research failure and the understanding and application of theory.

Objective: To evaluate the feasibility of quantitative analysis of dynamic 3-dimensional contrast-enhanced ultrasound (3D-CEUS) for treatment effects of microwave coagulation on xenograft tumors in nude mice. Methods: BALB/c nude mice transplanted of HepG2 cells were divided into treatment group(n=16) and control group(n=16). The tumors were treated by incomplete microwave coagulation in the treatment group when their maximum diameters were about 0.8~1.0 cm. The baseline ultrasound and dynamic 3D-CEUS were performed on 1 d before treatment, 3 d after treatment, 7 d after treatment and 14 d after treatment. Time-intensity curves of the tumors were obtained by fitting. The quantitative parameters were also obtained, including peak intensity (PI), time to peak (TTP), mean transit time (MTT), slope (S), area under the curve (AUC), area under the curve of wash-in (AWI), and area under the curve of wash-out (AWO). Results: There were significant differences(P=0.029) between the two groups in PI, S, AUC, AWO on 3 d and 14 d. The differences in other parameters were not statistically significant (P>0.05). On 1 d before treatment and 7 d after treatment, none of the parameters had statistically significant difference (P>0.05). Conclusions The quantitative analysis of dynamic 3D-CEUS is feasible to assess the treatment response on xenograft tumors in nude mice.

Objective To evaluate the imaging features of hepatic epithelioid angiomyolipoma (EAML) on contrast-enhanced ultrasound (CEUS). Methods The imaging features of pathologically proved hepatic EAML lesions in 17 patients who had undergone baseline ultrasound and CEUS examinations were evaluated retrospectively. Results All of the cases were single lesion.70.6% (12/17) of the lesions were hypoechoic on ultrasound and 82.4% (14/17) of the lesions were heterogeneous.Flow signals were detected in 88.2% (15/17) of the lesions and 82.4% (14/17) of the lesions showed ringlike or arc arterials peripherally on color Doppler flow imaging (CDFI).The value of RI was 0.38-0.56.On CEUS,all lesions exhibited remarkable hyperenhancement in the arterial phase. 29.4% (5/17) of the lesions showed branched enhancement,70.6% (12/17) of the lesions showed diffusely entire enhancement.Strong ring-like enhancement peripherally was detected in 29.4% (5/17) of the lesions.88.2% (15/17) of the lesions were detected homogeneously enhancement during the peak period on CEUS. Washout of contrast agent and hypoechogenicity to surrounding liver tissue during portal or late phase were observed in 41.2% (7/17) and 64.7% (11/17) of the cases retrospectively.Conclusions The combination of real-time CEUS and baseline US can improve the correct diagnosis of hepatic EAML.

Objective To evaluate the correlation and consistency of dynamic three-dimensional contrast-enhanced ultrasonography ( 3D-CEUS ) and two-dimensional contrast-enhanced ultrasonography (2D-CEUS) in the time-intensity curve ( TIC) parameters of quantitative analysis in liver neoplasms. Methods Thirty patients were examined with 2D-CEUS and dynamic 3D-CEUS.The dynamic raw data were analyzed by quantitative analysis software. The regions of interest were manually selected around the entire lesion;TIC curves were generated and fitted respectively. Quality of fit ( QOF) was used to evaluate the degree of fit between the fitted curve and the initial ccoefficients of S,PI and AUC were 0.92,0.72 and urve. The corresponding 2D-CEUS and 3D-CEUS quantitative parameters of the same lesion were compared,including peak intensity ( PI),slope ( S),area under curve (AUC),time to peak (TTP) and mean transit time (MTT). The correlation of the intensity-related quantitative parameters and the consistency of the time-related quantitative parameters were analyzed between the two kinds of CEUS. Results The consistency of time related quantitative parameters,including MTT and TTP,were 0.97 and 0.96,and the correlation were 0.94 and 0.93. The correlation 0.65,respectively. Conclusions The quantitative results of 3D-CEUS are stable and reliable,and have fair concordance with 2D-CEUS. Dynamic 3D-CEUS can be used for clinical evaluation of the blood perfusion of liver neoplasms.

Objective To investigate the imaging features of dysplastic nodules with a focus of hepatocellular carcinoma ( DN-HCC ) on contrast-enhanced ultrasound ( CEUS ) and to improve the diagnostic accuracy . Methods The clinical data of 60 patients and CEUS imaging of 62 hepatic nodules [DN-HCCs , n =54 ;dysplastic nodules (DN) , n =8] pathologically proved were reviewed retrospectively . According to Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) , the lesions were categorized . Results Significantly different CEUS patterns between DN-HCCs and DNs were observed ( P < 0 .05) . During the arterial phase ,54 DN-HCC lesions showed various enhancement patterns [ hypervascular ,59 .3％ ( 32/54 ) ;nodule-in-nodule ,9 .3％ ( 5/54 ) ;isovascular ,13 .0％ ( 7/54 ) and hypovascular ,18 .5％ (10/54)] . Of the 54 DN-HCC lesions ,44 .4％ (24/54) showed washout during the late phase .Of the 8 DN lesions ,62 .5％ (5/8) showed iso-enhancement during the arterial phase ,25％ (2/8) showed hypo-enhancement ,and 12 .5％ (1/8) showed hyper-enhancement . No DN lesion showed washout during the late phase .According to CEUS LI-RADS (LR) algorithm ,27 .8％ (15/54) DN-HCCs were LR-5 ,46 .3％ (25/54) DN-HCCs were LR-4 ,25 .9％ (14/54) DN-HCCs and 100％ (8/8) DNs were LR-3 . Regarding hyper-enhancement ( including local hyper-enhancement ) during the arterial phase or hypo-enhancement (including local hypo-enhancement) during the late phase as the diagnostic standard of DN-HCC , the diagnostic sensitivity , specificity and accuracy value were 83 .3％ , 87 .5％ and 83 .9％ , respectively . Conclusions The imaging features of hyper-enhancement during the arterial phase or hypo-enhancement during the late phase on CEUS are useful to diagnose DN-HCCs .