Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

Objective To investigate the knowledge-attitude-practice(KAP)of drug application among university students in Karamay,to analyze potential risk factors of medication risk.Methods Using the convenience sampling method,the basic information,current status of the KAP of medication of university students in Karamay were collected through online and offline questionnaire.Multiple linear regression was performed to analyze the influence of different characteristics of the research objects on KAP concerning medication risk.Results A total of 948 valid questionnaires were retrieved,the interviewees were mostly aged between 18 and 20 years old(55.06％),females(63.92％)were more than males(36.08％).The mean scores of knowledge,behavior,education and attitude towards medication among university students were(36.17±11.82),(31.04±9.17),(11.66±4.66)and(11.50±3.53)respectively.Most university students had good drug use habits and considered it necessary to acquire knowledge about safe drug use through different ways and forms,but they lacked awareness on safe drug use in terms of purchasing drugs,storing drugs,drug use behavior and drug use education.Multiple linear regression analysis showed that the major of study was an influential factor in medication knowledge(P＜0.01),with pharmacy majors demonstrating better mastery.It also in medication behavior(P＜0.01),with pharmacy majors exhibiting more standardized practices.Gender was an influential factor in attitudes toward medication education(P＜0.05),with females showing more positive attitude.Conclusion The knowledge of drug application among university students in the city is relatively good,and they have good medication habits.However,there are shortcomings in their medication behavior and education.It is necessary to actively carry out targeted medication education activities to promote safe and rational medication among university students.

Objective To observe the value of 3.0T multimodal MRI for preoperative evaluation of T stage and therapeutic efficacy of neoadjuvant for rectal cancer.Methods 3.0T multimodal MRI data,including T1WI,T2WI/diffusion weighted imaging(DWI),dynamic contrast enhanced MRI(DCE-MRI)and intravoxel incoherent motion DWI(IVIM-DWI)of 150 patients with rectal cancer were retrospectively analyzed,and the value of different sequences for evaluating T stage and therapeutic efficacy of neoadjuvant for rectal cancer were assessed.Results The sensitivity,specificity and accuracy of T1WI,T2WI/DWI,DCE-MRI and IVIM-DWI for evaluating T1-T2 and T3-T4 stage rectal cancer were all significantly different(all P＜0.05).The diagnostic efficacy of DCE-MRI and IVIM-DWI were all higher than that of T1WI and T2WI/DWI(all P＜0.05).Combination evaluation of DCE-MRI and IVIM-DWI for T stage of rectal cancer had good consistency with pathological results(Kappa=0.943,P＜0.05).Significant differences of volume transfer constant(Ktrans),true diffusion coefficient(D)and apparent diffusion coefficient(ADC)were found among different T stage rectal cancers(all P＜0.05).Totally 80 patients received neoadjuvant therapy,and significant differences of Ktrans,D and ADC were noticed between patients with good(n=32)or poor efficacy(n=48)(all P＜0.05).The area under the curve(AUC)of Ktrans,D and ADC for evaluating therapeutic efficacy of neoadjuvant for rectal cancer was 0.774,0.837 and 0.758,respectively,of the combination of above three was 0.929,higher than that of single indexes(all P＜0.05).Conclusion Combination of 3.0T DCE-MRI and IVIM-DWI was helpful for preoperative evaluating T stage and therapeutic efficacy of neoadjuvant for rectal cancer.

Objective:To evaluate the clinical application value of endoscopic ultrasonography (EUS) in the etiological diagnosis of patients initially diagnosed with idiopathic acute pancreatitis (IAP).Methods:Clinical data of 128 patients who underwent further EUS and magnetic resonance cholangiopancreatography (MRCP) after initial diagnosis of IAP at the Gastrointestinal Endoscopy Center of the First Affiliated Hospital of Naval Medical University between January 2015 and February 2022 were collected and divided into a single-episode group (single-episode group, 51 cases) and a multiple-episode group (recurrent group, 77 cases) based on the number of AP episodes. The data and the diagnosis of the etiology of IAP in the two groups by EUS were analyzed and compared with the etiological diagnosis results of MRCP.Results:The differences on basic information such as gender, age, history of smoking, history of alcohol consumption, family history of pancreatic disease, history of cholecystectomy, abnormality of liver function, and severity of pancreatitis between the single-episode group and recurrent group of IAP patients were not statistically significant. The etiology was clarified in 79 (62%) IAP patients after EUS examination, of which 55 (43%) cases had biliary disease (gallstones, microlithiasis, biliary sludge) and 24 (19%) cases had pancreatic disease (chronic pancreatitis, pancreatic divisum, pancreatic interstitial or pancreatic ductal changes). The percentage of patients with biliary disease as the cause of IAP was significantly higher in the single-episode group than in the recurrent group (59% vs 32%), while the percentage of patients with pancreatic disease as the cause of IAP was higher in the recurrent group than in the single-episode group (25% vs 10%), with statistically significant differences ( P values=0.004 and 0.035, respectively). The performance of EUS in diagnosing the etiology of IAP was significantly higher than that of MRCP (62% vs 19%, P=0.032), where EUS was more accurate in detecting biliary microlithiasis or biliary sludge (43% vs 9%, P<0.01). EUS was also superior to MRCP in identifying subtle changes in chronic pancreatitis lesions (small pancreatic nodules, patchy hyperechogenicity, etc.) and intraductal papillary mucinous neoplasms(17% vs 7%, P<0.05), but was inferior to MRCP in identifying pancreatic divisum (2 cases vs 4 cases). Conclusions:In view of high diagnostic accuracy and safety of EUS in diagnosing biliary diseases, and based on the fact that most IAPs in China are due to biliary diseases, EUS based management strategy can be considered to be a reasonable approach for evaluation of IAP patients. The MRCP can be used as a supplement to the EUS to identify a controversial etiology.

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.

Objective:To analyze the effects of prescription reviews of key monitored drugs using the drug regulatory platform in a district of Shanghai, and the influencing factors for the rate of unqualified prescriptions.Methods:A drug regulatory platform in a district in Shanghai began to implement prescription reviews since June 2018, extracting the reviewed prescriptions of all key monitored drugs and related information from June to December. Taking the unqualified rate of prescription in June as the baseline data, the χ2 test and the logistics regression model were used for data analysis. Results:From June to December 2018, clinical pharmacists reviewed 19 084 outpatient and emergency prescriptions and 10 607 inpatient prescriptions. The unqualified rates of outpatient and emergency prescriptions and inpatient prescriptions dropped from 16.52% and 23.28% in June to 4.45% and 13.80% in December, respectively. Logistics regression analysis showed that the rate of unqualified reviews of outpatient and emergency prescriptions was lower than that of inpatient prescriptions, and the rate of unqualified prescriptions in hospital was significantly lower than that in community health service centers; the rate of unqualified prescriptions for auxiliary drugs and nutritional drugs was significantly lower than that of antibacterial drugs.Conclusions:The prescription reviews of key monitored drugs can effectively promote the rational use of drugs. In the future, it is recommended to strengthen technical support for community health service centers and professional training for clinicians and pharmacists.

Objective:To evaluate diagnostic value of contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for pancreatic cystic lesions.Methods:Endoscopic and clinical follow-up data of patients with pancreatic cystic lesions diagnosed by EUS in Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University with CEH-EUS video from March 2013 to April 2020 was retrospectively analyzed.Results:A total of 36 patients were included. There were 16 cases of serous cystadenomas (SCA), 10 cases of mucinous cystic neoplasm (MCN), 5 cases of intraductal papillary mucinous neoplasms (IPMN, 3 with complex type, 2 with main pancreatic duct type) and 5 cases of pancreatic pseudocyst (PPC). 87.5%(14/16) of SCA and 86.7%(13/15) of MCN+ IPMN had hyperenhanced cystic wall with obvious peak and similar washout as surrounding tissue, whereas only 20%(1/5) PPC had hyperenhanced cystic wall. The hyperenhancing effect of PPC was significantly lower than that of SCA and MCN+ IPMN ( P=0.0035 and P=0.0048, respectively ). Mural nodules were detected in 17 cases of pancreatic cystic lesions by EUS, of which 3 cases had hyperenhanced mural modules and 14 cases had hypoenhanced mural nodules by CEH-EUS. Patients showing hyperenhanced mural modules were all finally diagnosed as pancreatic malignancy (1 IPMN, 2 MCN), and the accuracy was 100%. Conclusions:CEH-EUS can have a obvious advantage of differentiating pseudocyst and other pancreatic cystic lesions, while not very useful for differentiating SCA and MCN. Pancreatic cystic lesions showing hyperenhanced mural nodules under CEH-EUS may imply malignancy potential.

The paper aims to study and compare the effects of Scutellaria baicalensis leaves (SLE) and Scutellaria baicalensis tea (STE) water extracts on the lifespan of Drosophila melanogaster, and explore their anti-aging mechanism through metabolomics. Lifespan, food intake and fertility were measured after administering different doses of SLE and STE to a Drosophila natural aging model, and the metabolic profile of Drosophila was analyzed by metabolomics and multivariate statistical methods. The results showed that SLE and STE (1, 3 g·L^-1) could significantly prolong the average lifespan, median life and maximum lifespan of male Drosophila, improve the fertility of Drosophila, and had no effect on the food intake. Through metabolomics technology, 14 differential metabolites related to aging were found, involving a total of five metabolic pathways. All differential metabolites were reversed after STE intervention, while 13 differential metabolites were reversed after SLE intervention. The results suggest that SLE and STE can delay aging of Drosophila, and the anti-aging mechanism is related to energy metabolism.

Fournier gangrene is a relatively rare clinical critical disease, and its clinical symptoms are not specific and easily unrecognized by some clinicians. It has the features of acute onset, quick development, severe illness, and often accompanied by infection shock which is seriously life-threatening. It is difficult in treatment with high medical costs and long length of hospitalization, which increases pain for patients and relatives and brings heavy economic and psychological burden on patients, society, and medical workers. By reviewing the literature home and abroad and combined with clinical practice, I summarize the researches on concept, epidemiology, clinical manifestation, diagnosis and treatment of Fournier gangrene, in order to provide reference for vast number of clinical workers.

Objective:To evaluate the clinical results of reduction and fixation via fibular osteotomy for treatment of old ankle fractures involving the posterior malleolus in middle-aged and elderly patients.Methods:A retrospective case series study was made for 13 middle-aged and elderly patients with old ankle fractures involving the posterior malleolus treated from July 2013 to March 2018 in Sixth People's Hospital Affiliated to Shanghai Jiao Tong University. There were 2 males and 11 females, with age of 48-63 years (mean, 54.8 years). The mean surgical period was 8-18 weeks from injury (mean, 9.6 weeks). According to Haraguchi classification, all posterior malleolar fractures were type I. According to Lauge-Hansen classification, there were 2 patients with pronation-external rotation type and 11 with supination-external rotation type. All patients underwent open reduction and fixation via fibular osteotomy. Bone healing time and postoperative complications were recorded. Clinical results were assessed by visual analogue scale (VAS) score and American orthopedic foot and ankle society (AOFAS) ankle-hind score.Results:All patients were followed up for average 20.3 months (range, 9-36 months). All patients had bone union, with the mean healing period of 12-15 weeks (average 14.8 weeks). No infection, implant loosening or breakage occurred after operation. X-ray film of one patient suggested mild traumatic arthritis. At the latest follow-up, VAS was improved to (1.0±0.2)points compared to pre-operative (5.3±0.6)points ( P<0.05), and the AOFAS ankle-hind score was improved to (85.2±7.4)points compared to pre-operative (42.4±6.7)points ( P<0.05). According to the AOFAS ankle-hind score, the results were excellent in 4 patients, good in 8, moderate in 1, with the excellent and good rate of 92%. Conclusion:For old ankle fractures involving the posterior malleolus in the middle-aged and elderly patients, reduction and fixation via fibular can reduce postoperative complications, facilitate bone healing, relieve ankle pain and improve function recovery.