Objective:To establish UPLC characteristic spectrum of Hujiao standard decoction and the determination method for the content of piperine.Methods:15 batches of freeze-dried powder of Hujiao standard decoction were prepared according to the traditional decocting method. The range of paste yield was determined, and the UPLC characteristic spectrum of the standard decoction was established. High-resolution mass spectrometry and control products were used to identify common peaks. Based on the common peak area, the weights of each peak were compared using entropy weight method, and correlation analysis and similarity evaluation were conducted using clustering analysis and grey correlation method; a method for determining the content of piperine in Hujiao decoction pieces and freeze-dried powder of standard decoction was simultaneously established, and the transfer rate was calculated.Results:The extraction rate of 15 batches of freeze-dried powder of Hujiao standard decoction ranged from 10.4% to 16.8%, with an average of 14.0%. The content of piperine ranged from 12.2 to 30.0 mg/g, with an average of 18.5 mg/g, and the transfer rate ranged from 4.0% to 7.8%, with an average of 5.8%. Six common peaks were identified in the established characteristic spectrum and identified by high-resolution mass spectrometry and control products respectively. Peak 1 was N-trans-feruloyltyramine, peak 3 was piperine and the similarity was 0.959-1.000. Clustering analysis and grey correlation analysis showed that there was little difference between quality of Piperis Fructus and origins.Conclusion:In this study, the characteristic spectrum and content determination method of freeze-dried powder of Hujiao standard decoction are established, which can provide references for quality detection and control of Hujiao standard decoction or its derivative products.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

To investigate the clinical and genetic characteristics of patients with idiopathic hypogonadotropic hypogonadism (IHH), the clinical data of 23 patients with IHH were retrospectively analyzed. Gene analyses were accomplished with whole-exome sequencing (WES) and Sanger sequencing. Functional prediction of mutation sites was conducted using two bioinformatics platforms, SIFT and Polyphen. Among the 23 patients with IHH, 9 patients carried prokinin 2 (PROKR2) gene mutations including 4 missense mutations (p.W178S, p.Y113H, p.A103V, p.R164Q), and 1 frameshift mutation (p.D42delinsDED), the remaining 14 cases were found negative in gene sequencing. Functional prediction showed that the above mutations may affect protein function suggestive of a pathogenic role of PROKR2 mutation in the patients. There were no significant differences in the levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol between the IHH patients with PROKR2 gene mutation and those without. PROKR2 gene mutation might associated with IHH, and the mutations reported in the present study could enrich the pathogenic spectrum of genes.

Objective:To explore clinical evaluation and genetic analysis of patients with idiopathic hypogonadotropic hypogonadism (IHH).Methods:The clinical data and phenotypes of 22 patients with IHH diagnosed and treated in our department were reviewed and analyzed. Whole-exome sequencing(WES)and Sanger method were used for variant analysis and verification.Results:Among the 22 cases of IHH probands, 12 cases of Kalman syndrome (KS) and 10 cases of IHH (nIHH) with normal sense of smell. On physical examination, males showed short penis, small testicles, small or inconspicuous laryngeal knots, and a sharp voice. Mammary gland development, mammary gland dysplasia, primary amenorrhea, etc. in women. Sex hormone examination: Follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2) levels are reduced or at the lower limit of normal. There were nine missense variants of CHD7 gene in 8 patients. Based on the American College of Medical Genetics and Genomics guidelines, the c. 307T>A(p.Ser103Thr), c.3143G>A(p.Gly1048Glu), c.6956G>T(p.Arg2319Leu) and c. 3145A>T(p.Ser1049Cys) variants of CHD7 gene were predicted to be likely pathogenic (PS1+ PP1+ PM2, PM2+ PM6+ PP2+ PP3, PM2+ PM5+ PM6+ PP2+ PP3 and PM2+ PM6+ PP2+ PP3), the remaining 14 cases of IHH patients had negative genetic screening. Conclusion:CHD7 gene variants may be related to IHH disease.

Objective To establish a convenient and efficient method to detect Environmental endocrine disruptors (EDCs) in atmospheric particulate matter. Methods Atmospheric total suspended particles (TSP) was sampled through glass fiber filter paper in a medium-flow TSP sampler at a flow rate  of 100L/min for 2 hours. The filter paper sample was then subjected to the treatments as follows: (1) The samples were extracted with acetone and dichloromethane (3:2,v/v) from glass fiber filter paper. (2) Ultrasonic cleaning for 30 minutes. (3) Centrifugation at 2,500r/min for 20 minutes. (4) The supernatant was dried out in water baths at 55℃, and then acetonitrile was added to make the volume constant. Chromatographic condition was : HPLC-FLD ( λ_ex=275nm，λ_em=312nm) . Results The content of OP, NP and BPA in the standard series showed a good linear relationship with their respective peak areas, and all the correlation coefficients were greater than 0.99. The detection limits for BPA, OP, NP were 9.80 ng/ml, 5.60 ng/ml, and 5.30 ng/ml, respectively, and the recoveries were 92.10%~127.00%, 83.90%~97.40%, and 83.70%~101.20%, respectively. The RSD for the inter-and intra-day was less than 5%. Conclusion The method was simple, rapid, and accurate, which could be used for the detection of environmental endocrine disruptors in atmospheric particulate matter.

The 17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is a rare disease. The clinical characteristics and gene mutation of 2 late-diagnosed 17-OHD patients with testicular tumor admitted to our hospital from March 2018 to February 2019 were analyzed retrospectively. The two 17-OHD patients were female (46, XY). Laparoscopic abdominal exploration found undeveloped testicles in grey-yellow or grey-red in the groin and iliac fossa. The testicles were removed and showed malignancy in pathology study. Sequencing of the CYP17A1 gene identified c.1247G>A/c.1427T>C and c.985_987delTACinsAA/c.1306G>A complex heterozygous mutations. Taking together, the possibility of 17-OHD should be considered in patients with hypertension, hypokalemia, adrenal adenomatoid hyperplasia together with 46, XY gonadal dysplasia, so as to make early diagnosis and treatment, and avoid dysplastic testicular turning to malignancy.

Objective:To explore the clinical effect of digital endoscopic-assisted one-stage rhinoplasty and septoplasty by using subjective and objective methods.Methods:Thirty-two patients with skeletal crooked nose and nasal septum deviated who underwent endoscopic-assisted rhinoplasty and septoplasty were included in this study from January 2015 to January 2020. This study used objective measurements such as 3D digital imaging technology and CT scans, as well as subjective measurements such as Visual Analogue Scale (VAS), Rhinoplasty Outcomes Evaluation (ROE) scale, Nasal Obstruction Symptom Evaluation (NOSE) and Functional Rhinoplasty Outcome Inventory (FROI-17) to evaluate the crooked nose morphology and nasal respiratory function before and after surgery.Results:Compared with preoperatively, postoperative 3D facial imaging results showed that the deviation distance and deviation angle of the crooked nose were significantly improved (both P<0.05), and the long-term effect of the operation was stable. Subjectively, the patient＇s appearance VAS score and ROE score were significantly higher than those before surgery, while the NOSE score and FROI-17 score of nasal congestion symptoms were lower than those before surgery. Conclusions:Endoscope-assisted one-stage rhinoplasty and septoplasty can achieve the purpose of repairing the nose appearance and improving the nasal respiratory function at the same time. Through a combination of subjective and objective evaluations, our study found that this procedure had the advantages of minimally invasive, stable effect and shorter recover time; meanwhile, this procedure has high patients＇ satisfaction and is worthy of clinical promotion.

OBJECTIVE:To investigate the omeprazole off-label use and provide reference for rational drug use in clinic. METHODS:In retrospective survey,1838 omeprazole prescriptions were selected from outpatient department during Jun. 2014 to May 2017 by random number table. According to the latest drug instruction,whether the off-label use or not was determined. Off-label use was determined by reviewing domestic and foreign guidelines,literatures and Micromedex database. RESULTS:Among 1838 pre-scriptions,there were 1750 prescriptions of off-label drug use (95.21％),involving 13 items and 3 types of off-label drug use. Main type of off-label drug use was over-indication medication,involving 1747 prescriptions (96.47％). There was no statistical significance in the incidence of off-label drug use between digestive department and non-digestive department or among physicians at different levels(P>0.05). Among 13 items of off-label drug use,7 items were supported by evidence-based medicine evidence of domestic and foreign guideline,expert consensus/suggestion or literature reports,etc.;among which 1 item of off-label drug use were included in Micromedex grading system and other 6 items had no evidence-based medicine evidence. CONCLUSIONS:The phenomenon of omeprazole off-label use is widespread in outpatient department of the hospital,and some off-label drug use are sup-ported by evidences. There are differences in the quality of those evidences. It is suggested to standardize the off-label drug use to avoid legal risks and guarantee the safety of drug use for patients.

Objectives To investigate the diagnostic performance of the combination of ultrasound elastography and automated breast volume scanner (ABVS) in differentiation of benign and malignant breast imaging reporting and data system (BI-RADS) 4 breast lesions. Methods Data from 137 breast cancer patients (147 tumors) confirmed pathologically were analyzed. Each tumor was examined by ABVS and ultrasound elastography. All tumors were diagnosed as BI-RADS 4 by ABVS. With final pathology results as the gold standard, the predictive value in differentiating BI-RADS 4 breast lesions between ultrasound elastography and the combination of ultrasound elastography and ABVS were compared. Results There were 54 benign nodules and 93 malignant nodules in this study. The diagnostic sensitivity of ultrasound elastography and the combination of ultrasound elastography and ABVS were 94.6% and 98.9%,the specificity were 57.4% and 57.4%, the accuracy were 81.0% and 83.7%, the area under the curve were 0.858 and 0.965, respectively. The diagnostic performance of ultrasound elastography combined with ABVS was better than that of ultrasound elastography. Conclusions Ultrasound elastography have certain value in differential diagnosis of BI-RADS 4 breast lesions, especially when combining with ABVS, which will improve its diagnostic accuracy. Ultrasound elastography combined with ABVS can improve the detection rate of malignant lesions in BI-RADS 4 breast lesions and reduce the rate of preoperative biopsy, and it has a good application prospect.