Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, in vitro electrophysiology recordings, in vivo fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.

Objective To establish a risk prediction model,and to observe its value for predicting retained cesarean scar pregnancy(CSP)after ultrasound-guided curettage.Methods Data of 401 CSP patients who received ultrasound-guided curettage were retrospectively analyzed.The patients were randomly divided into training set(n=264)or validation set(n=137)at a ratio of 7:3.According to whether there was retained CSP at the lower segmental scar of uterine after ultrasound-guided curettage,the patients were divided into retained group or non-retained group.The variables with the biggest predictive value for retained CSP after ultrasound-guided curettage were selected with LASSO regression,and the independent risk factors were screened using multivariate logistic regression,and then a nomogram model was established.Results The results of LASSO regression and multivariate logistic regression indicated that embedded depth of gestational sac in cesarean scar more than 1.13 cm,convexity of gestational sac,rich blood supply(Adler degree Ⅱ-Ⅲ),and pre-curettage serum β-human chorionic gonadotropin(HCG)more than 33 063.50 U/L were all independent risk factors for retained CSP after curettage(all P＜0.05).The calibration curve of nomogram predictive model established based on the above indexes was basically consistent with the ideal curve,and the model had good clinical benefits.Conclusion The established nomogram predictive model had good predictive ability for retained CSP after curettage.

OBJECTIVE：To establish the content determin ation method of ferulic acid ，verbascoside，ligustilide and astragaloside in Shengyu decoction lyophilized powder. METHODS ：HPLC method was adopted to determine 4 components in 3 batches of lyophilized powder. The determination of ferulic acid ，verbascoside and ligustilide was performed on Inertsil ODS-SP C 18 column with mobile phase consisted of methanol- 0.1％ phosphoric acid （gradient elution ）at the flow rate of 1.0 mL/min；detector was diode array detector ；detection wavelength was set at 330 nm；column temperature was 30 ℃，the sample size was 10 μL. The determination of astragaloside was performed on Kromasil C 18 column with mobile phase consisted of acetonitrile-water （32∶68，V/ V）；detector was evaporative light scattering detector ；the drift tube temperature wa s 100 ℃，the carrier gas （air）flow rate was 2.5 L/min at the flow rate of 1.0 mL/min；column temperature was 30 ℃，the sample size was 10 μL. RESULTS：The linear ranges of ferulic acid ，verbascoside，ligustilide and astragaloside were 0.050 15-10.03 μg（r＝0.999 8），0.067 80-13.56 μg（r＝ 0.999 9），0.057 30-11.46 μg（r＝0.999 5），1.128-11.28 μg（r＝0.999 3），respectively. The detection limits were 2.12×10－4，1.30× 10－3，8.02×10－4，1.09×10－3 μg，respectively. The limit of quantification were 7.43×10－4，3.87×10－3，2.34×10－3，3.36×10－3 μg， respectively. RSDs of precision ，stability（12 h）and reproducibility tests were all lower than 2％（n＝6）. Average recovery rates were 99.6％（RSD＝0.83％，n＝6），100.9％（RSD＝1.07％，n＝6），98.8％（RSD＝0.84％，n＝6）and 101.3％（RSD＝0.99％， n＝6），respectively. The contents of ferulic acid ，verbascoside，ligustilide and astragaloside in 3 batches of samples were 1.225-1.248， 0.413-0.424， 0.325-0.332， 0.394-0.404 mg/g， respectively （RSDs among batches were lower than 1.5％ ）. CONCLUSIONS：Established method is stable ，reproducible，rapid and accurate for the content determination of ferulic acid ， verbascoside， ligustilide and astragaloside in Shengyu

Objective:To explore the pathogenic variants of a family with syndromic deafness by high-throughput sequencing.Methods:The family was from Puyang City, Henan Province, and had four members, including two with syndromic deafness. The proband and his sister had congenital deafness, and their parents had normal phenotypes. The clinical phenotype of the family was characterized using clinical examinations and pedigree analysis. The clinical examinations included imaging examination, audiometry (pure tone audiometry, acoustic immittance, brainstem auditory evoked potential, and otoacoustic emission), vestibular function test, and ophthalmic examination (visual acuity test, visual field test, fundus examination, visual evoked potential, and electroretinogram). Target exome sequencing of 129 known deafness genes and bioinformatics analysis were used to screen suspected pathogenic variants. Sanger sequencing and minigene assay were used to verify and functionally investigate the mutation detected, respectively. According to the standards and guidelines for interpreting genetic variants proposed by the American College of Medical Genetics and Genomics, the variants c.6049G>A and c.8699A>G were classified as pathogenic/likely pathogenic, and the variant c.9856C>G was classified as variants of uncertain significance.Results:The probands and his sister had severe sensorineural hearing loss with decreased binocular vision, night blindness, decreased peripheral visual field sensitivity and partial visual field defect, and normal vestibular function. Both of them had three CDH23 mutations, including CDH23 (NM_022124.5) c.6049G>A (p.Gly2017Ser),c.9856C>G (p.His3286Asp), and c.8699A>G (p. Asp2900Gly), The first two were inherited from the father, and the last one was from the mother. The missense variants c.9856C>G and c.8699A>G were not included in the gnomad database. The missense mutation c.6049G>A was located in the last position of exon 46 and was predicted to affect splicing by bioinformatics software. The minigene experiment showed that the mutation cause exon skipping of exon 46, resulting in an abnormal protein. Conclusions:Compound heterozygous variations of the CDH23 are the leading cause of USH1D in the family. This study confirms that the compound heterozygosity of splicing and missense variants of the CDH23 gene could lead to USH1D.

SUMMARY Pheochromocytomaisrareinpregn’ancy.Clinicalfeaturesofacaseofpheochromocytoma during pregnancy in the Peking University People’s Hospital was investigated and the literature reviewed to discuss the diagnosis and treatment of this disease.The patient manifested with hypertension and pro-teinuria,who was easily misdiagnosed with gestational hypertension disease.When she was transferred to our hospital,the symptoms such as,paroxysmal palpitation,dizziness,vomiting were noticed,and the possibility of pheochromocytoma was considered due to the accompanying abdominal mass.An emergent cesarean section was performed successfully due to preterm labor during the treatment of the disease.Af-ter the delivery the drug preparation continued.And the laparoscopic resection of pheochromocytoma pro-ceeded when the blood pressure was steady.The patient recovered fully after the surgery.The final diag-nosis of pheochromocytoma was confirmed with the pathology.Its diagnosis and treatment experiences could improve our understanding and treatment of secondary hypertension due to pheochromocytoma in pregnancy.

Objective:To assess the changing trends in Gleason score (GS)of Chinese prostate carci-noma (PCa)from January 1995 to December 2014.Methods:In the study,875 patients admitted to hospital from January 1995 to December 2004 (1995 -2004)and from January 2005 to December 2014 (2005 -2014)were divided into two groups.The mean levels and proportions of GS,primary and se-condary grades were studied.The patients were divided into four groups according to age: <60,60 -69,70 -79 and ≥80 years.Types of specimen included needle biopsy (NB),transurethral resection of the prostate (TURP)and radical prostatectomy (RP).Histological types were made up by acinar carci-noma and other types (including atrophic,pseudohyperplastic,foam,signet ring cell and ductal carcino-ma,and so on).The total prostate-specific antigen (tPSA)involved groups of <20.0 μg/L and ≥20.0 μg/L.We observed the mean levels and proportions of GS in age,types of specimen,histological types and total prostate-specific antigen in different periods,and used SPSS 17.0 software for statistical analysis.Results:Compared with 1995 -2004,the mean levels of GS,primary and secondary grades decreased 0.32 (P =0.003),0.19 (P =0.001)and 0.12 (P =0.016)in 2005 -2014,respectively. The proportions of ≤6 in GS increased 10.9% (P =0.003),and ≥8 decreased 14.0% (P <0.001). The difference of GS 7 was not statistically significant.In the primary grade,the ratio of grades≤3 in-creased 12.8% (P =0.001 ),and grade 4 decreased 7.4% (P =0.037),grade 5 decreased 5.5%(P =0.007).The ratio of secondary grades≤3 increased 7.6% (P =0.037).The difference of grades 4 and 5 was not statistically significant.Conclusion:GS in Chinese patients with PCa showed a down-ward trend,which is one of the notable features in the past 20 years in China.The types of specimen and age are important factors in GS,while the histological types and tPSA have less impact on the GS.

Objective To investigate the clinicopathological features of renal cell carcinoma (RCC).Methods From December 1956 to August 2012,the clinicopathological features of RCC were studied in 705 cases and related literatures were reviewed.Results The diameter of RCC ranged from 0.6 to 18.0 cm,which the average size was 4.6 cm.The proportions of the clear cell,papillary,multilocular clear cell,chromophobe and unclassified histologic subtype were 88.9％ (627/705),4.1％ (29/705),3.3％ (23/705),1.3％ (9/705) and 2.4％ (17/705),respectively.According to the Fuhrman grading system,the proportions of grade 1,2,3,4 were 19.0％ (116/612),58.3％ (357/612),18.1％ (111/612)and 4.6％ (28/612),respectively.The rates of invasion into the renal pelvis,perirenal fat and vascular were 10.9％ (66/603),10.6％ (64/603) and 4.8％ (29/603),respectively.Of 705 cases,464 (76.6％)cases were in T1,65 (10.7％) cases in T2,73 (12.0％) cases in T3,and 4 (0.7％) cases in T4.As to the lymph node and distant metastasis,the rate was 2.8％ (17/606) and 3.5％ (21/606).The percentages of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ RCC were 74.3％ (450/606),9.9％ (60/606),11.7％ (71/606) and 4.1％(25/606),respectively.The 3-,5-,10-and 15-year disease-specific survival rate for RCC was 92.8％,86.9％,76.8％ and 55.5％,respectively.To those patients with clear cell RCC,the disease-specific survival at the same time point was 92.8％,88.1％,77.4％ and 55.4％,respectively.Multivariate analysis showed that the stage was the only independent prognostic factor for RCC.Conclusions Tumor stage of RCC is the independent prognostic factor for disease-specific survival.The evaluation of renal sinus invasion and lymph node should be noted in the diagnosis of RCC.

Objective To investigate the genetic association between the inducible nitric oxide synthase (NOS) 2A gene and stroke with a history of coronary artery disease ( CAD). Methods 708 patients with stroke and 235 healthy controls were recruited in this study, and the stroke group was delaminated into 2 subgroups according to the history of CAD. SNP rs28944190, an A to C base change located in intron 22 of the gene, was used as a genetic marker. PCR-based restriction fragment length polymorphism analysis was applied to genotype rs28944190 (Hac Ⅲ site). Results The x2 test showed no association between patients with stroke and healthy controls. Of 708 patients, 94 had a history of CAD and the frequency of allele C of rs28944190 was significantly higher in patients with a history of CAD than those without (23.9% vs 16.6%, x2 =5.629, df= 1, P =0.018, OR = 1.580, 95% CI 1.083—2.306), especially in male patients (x2 = 8. 592, df= 1, P = 0. 003, OR = 1. 983, 95% CI 1. 255—3. 134). The frequency of genotype AA + AC of rs28944190 was significantly higher in patients with a history of CAD than those without such a history (47.9% vs 30. 8%, x2 = 10. 761, df= 1, P = 0. 001, OR = 2. 065, 95% CI 1.34—3.19), especially in male patients (x2 = 15. 762, df= 1, P =0. 000, OR =2. 985, 95% CI 1.74—5. 12). Conclusion The present study suggests that the NOS2A gene is unlikely to contribute to the etiology of stroke.

Objective To explore the effects of Baogan Jiedu Granule on lipid peroxidation of free radicals in acute liver injury mice induced by tripterygium glycosides.Methods Totally 60 mice were randomly divided into tripterygium glycosides model group,large-dose,medium-dose and small-dose groups of Baogan Jiedu Granule,Ganlixin group and control group.Each group was respectively perfused with the corresponding drug for 5 days and tripterygium glycosides were perfused once to make the model.The serum levels of ALT,AST,SOD,MDA and GSH-Px were measured.Results The serum levels of SOD and GSH-Px in model group decreased and MDA rose obviously.Compared with model group,Baogan Jiedu Granule of all doses could effectively decrease ALT,AST and MDA level and obviously improve GSH-Px level in each group.In addition,in the large-dose group SOD level was markedly improved(P