Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To investigate the clinicopathological features, immunohistochemical characteristics, differential diagnosis and prognosis of gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinomas.Methods:Two cases of gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma were collected at Fudan University Shanghai Cancer Center, Shanghai, China from 2017 to 2018. The clinicopathological characteristics were analyzed. Hematoxylin and eosin, and immunohistochemical stains were performed, and the relevant literatures were reviewed.Results:The two patients were both male, aged 60 and 74 years, respectively. Their symptoms were both abdominal pain. The tumor arose in the esophagogastric junction in case 1, and the cardia to the fundus and the posterior wall of the upper part of gastric body in case 2. Both tumors were present as an ulcerative mass. The patients died of tumor 11 months and 8 months after surgery, respectively. Histologically, the tumor cells arranged in sheets, nests, cords or trabecular patterns, and pseudoavleolar structure. The tumor cells were epithelioid with uniform morphology, while the tumors showed scant stroma and massive necrosis. Variable rhabdoid cells and multinucleated giant cells were seen in both cases. SMARCA4 encoding protein BRG1 was undetectable in both tumors, while SMARCB1 encoding protein INI1 was detected. The tumor cells were diffusely positive for vimentin and negative for epithelial marker (CKpan), gastrointestinal stromal tumor markers (CD117 and DOG1), myogenic markers (desmin and myogenin), melanoma markers (S-100 protein, SOX10 and HMB45), and lymphohematopoietic markers (LCA and CD20).Conclusions:Gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma is a rare and highly aggressive tumor with poor prognosis. The detection of subunits protein expression of SWI/SNF complex is important for diagnosis of the tumor.

Orthopedic 3D printed surgical navigational template is an instrument that is prepared by 3D reconstruction based on preoperative radiological data of the patient using computer-aided design (CAD) and 3D printing techniques. The 3D printed navigational template allows accurate intra-operative assessment of the relative spatial distance, angular relationship, direction and depth. The application of 3D printed navigational template technique in orthopedics surgeries achieves the conversion of preoperative planning from 2/3D graphics to 3D models, and provides a new method for individualized and precise treatment. Herein we review the evolution, clinical application, and basic classification of 3D printed navigation template technique, analyze its advantages and disadvantages, and discuss the current problems and the future development of this technique.
Computer-Aided Design ; Humans ; Orthopedic Procedures ; Printing, Three-Dimensional

Objective To investigate the risk factors of acute pancreatitis after endoscopic retrograde chloangiopancreatography (ERCP).Methods Clinical date of 1 041 patients who underwent therapeutic ERCP from January 2016 to August 2017 in department of gastroenterology,Zhongnan Hospital of Wuhan University,were retrospectively studied.Among them post-ERCP pancreatitis developed in 53 patients (PEP group) and the remaining 988 patients were assigned in the non-PEP group.The clinical characteristics,procedures of ERCP,gastrointestinal symptoms and laboratory findings after ERCP were compared between two groups.The SPSS software (version 22.0) was applied to analyze the risk factors of PEP.Results The overall incidence rate of PEP was 5.09％ (53/1 041).There were statistic difference in the number of white cells [8.56(5.43,12.23)× 109/L vs.7.12(5.58,9.20)× 109/L,Z=-2.122] and the ratio of neutrophils [0.82 ± 0.11 vs.0.76 ± 0.12,t=-3.612] after ERCP operation;the incidence of endoscopic sphincterotomy (EST) [60.37％(32/53) vs.43.72％(432/988),x2=5.646] and endoscopic papillary balloon dilation (EPBD)[50.94％(27/53) vs.33.00％(326/988),x2=7.230] during operation,and periampullary diverticula [35.85％(19/53) vs.52.98％(523/988),x2=4.619] (all P＜0.05).Logistic analysis indicated that the ratio of neutrophils was independent risk factor of PEP(OR=1.058,95％CI:1.019-1.098,P=0.003).Conclusion The number of white cells,the ratio of neutrophils after ERCP and endoscopic sphincterotomy,endoscopic papillary balloon dilation and periampullary diverticula are associated with PEP,while the ratio of neutrophils is the independent risk factor of PEP.

Objective To explore the feasibility of oxygen saturation related diffusion index for assessing oxygenation status,and to establish the critical value of the oxygen saturation related diffusion index,so as to provide more approaches to monitoring oxygenation status.Methods A total of 30 patients with acute respiratory distress syndrome (ARDS) receiving mechanical ventilation support were retrospectively reviewed.Totally 340 cases were collected at corresponding time points,and were divided into mild,moderate and severe groups according to ARDS Berlin criteria.Results There was a positive correlation between oxygen saturation related diffusion index and oxygenation index (r=0.698,P＜0.001);the critical value between the moderate and severe groups of oxygen saturation related diffusion index was 171(sensitivity 84.7％,specificity 68.2％),and the critical value between mild group and moderate group was 440 (sensitivity 56.9％,specificity 91.9％).Conclusion The oxygenation index was consistent with the oxygen saturation related diffusion index in judging the oxygenation status of ARDS patients.As a noninvasive and continuous index,the oxygen saturation related diffusion index provides a new method for nursing assessment.

Objective To explore whether oxygen saturation-related dispersion index can be used as a non-invasive index for nurses to monitor ARDS patients' oxygenation and conditions.Methods Totally 23 patients with mechanical ventilation-associated complication and ARDS admitted in Peking Union Medical College Hospital between April 2015 and April 2016 were reviewed. Their PaO2, SpO2, PEEP and FiO2 values were recorded, and oxygenation index (OI) and oxygen saturation-related dispersion index were calculated for 132 case-times, respectively.Results The patients in the death group showed lower OI and oxygen saturation-related dispersion index than the patients in the survival group (P<0.05). The difference in oxygen saturation-related dispersion index between the light, middle and heavy groups were statistically significant (P<0.05).Conclusions Oxygen saturation-related dispersion index can be used to determine the prognosis of ARDS patients and the severity of the disease, especially the conditions of severe ARDS patients. As a non-invasive and continuous indicator, it provides a new measure for the nursing assessment of patients with mechanical ventilation-associated complication and ARDS.

Biliary stent has been utilized in the patients of benign and malignant biliary strictures and biliary fistula who are unsuitable or unwilling to operate.Its short-term curative effect is distinct,while the long-term effect is relatively poor,because the long-term application is affected by stent blocking and biliary ducts restenosis.Therefore,the research and development of new biliary stents,such as biodegradable stent and covered stent,are the main trend of the current development,which will be of profound significance for the biliary tract disease.

0bjective To observe the different brain activation of acupuncture and electroacupuncture on healthy subjects and healthy subjects.Methods The different brain activation involved in heroin addiction between healthy subjects and addicts was detected by fMRI.Acupuncture point used in present study Was Zusanli (ST 36).Results Different brain activations between healthy subjects and addicts during electroacupuncture were hypothalamus(X0,Y2,Z9,t=7.36,P<0.01),anterior cingulate(X5,Y49,Z8,t=4.11,P<0.01),tempo-ral gyrus(X61,Y12,Z8,t=3.05,P<0.01).The difference of activated regions during conventional acupuncture between healthy subjects and heroin addicts was thalamus(X2,Y16,Z12,t=2.87,P<0.01),parahippocampus (X17,Y52,Z3,t=3.14,P<0.01),and hypothalamus(X0,Y2,Z9,t=6.98,P<0.01).Conclusion Regions with significant activation detected by fMRI are different during acupuncture in heroin addicts and in the healthy subjects.Notably,the hypothalamus activation is more robust in the addicts than in the healthy subjects during ac-upuncture stimulation.

Objective To study the expression of secondary lymphoid-tissue chemokine (SLC)、 CCR7 and its correlation with clinical pathology and lymphangiogenesis in pancreatic adenocarcinoma (PAC). Methods The tissue specimens including PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were obtained from 30 patients with PAC. The expressions of SLC and CCR7 in these tissues were assayed by immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR). MIND marked by VEGFR-3 was detected by morphometric analysis, and the relationship between MLND and clinical pathology of PAC was analyzed. Results In all the specimens, the positive rates of SLC protein in PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were respectively 16. 7%, 43. 3%, 76. 7% and 46. 6%. The positive rates of CCR7 protein in PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes were respectively 76. 7%, 66. 7%, 30. 0% and 70. 0%. The results of RT-PCR and fluorescence quantitative real-time PCR indicated that the expression levels of CCR7 mRNA in PAC tissues, the cancerous peripheral tissues and peripheral lymph nodes were higher than that in the normal pancreatic tissues ( P <0. 01 ). There was no significant correlation between the expression of SLC protein with MLVD of PAC ( P > 0. 05 ). There was 23 specimens that the CCR7 protein was positive, and among these specimens the MIND was higher than that in negative group of CCR7 protein (P = 0.004). Conclusions The expression of SLC was not related to lymphatic metastasis and TNM stages of PAC. The expression of CCR7 was significantly associated with lymphatic metastasis and TNM stages of PAC, and the high expression of CCR7 in PAC tissues was significantly associated with lymphangiogenesis of PAC.

Objective To analyze the intratumoral and peritumoral microvessel density (MVD) and microlymphatic vessel density (MLVD) in pancreatic cancer and record the expression of vascular endothelial growth factor(VEGF)-C and VEGF-D. And to explore the significance of VEGF-C and VEGF-D during the lymphatic metastasis and development of pancreatic cancer. Methods The expression of VEGF-C and VEGF-D, VEGF-R3, CD34 were assayed by immunohistochemical staining in 30 cases of pancreatic cancer tissues. Results The positive rates of VEGF-C and VEGF-D protein in the central portion of tumors (30% and 16.7%) were significantly lower than those in the marginal portion (73.3% and 56.7%), P <0.01. The group with high expression of VEGF-C and VEGF-D in the marginal portion had significantly higher incidences of lymph node metastasis, lymphatic invasion and venous invasion( P <0. 01 ). MLVD in both of the VEGF-C and VEGF-D positive groups was higher than that in the negative groups( P <0. 01 ), and the lymph node me-tastasis increased. MVD in VEGF-C positive group was significantly higher than that in the negative group. MVD had no significant difference between VEGF-D positive and negative group ( P =0. 07). Conclusions The expression of VEGF-C and VEGF-D in the marginal portion of tumor is significantly correlated with lym-phatic metastasis in pancreatic cancer patients, and may induce lymphangiogenesis. VEGF-C may play an im-portant role in the regulation of angiogenesis and lymphangiogenesis in pancreatic cancer, and VEGF- D maybe only participate in the regulation of lymphangiogenesis.