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 report a case of germinated teeth of the left mandibular second molar diagnosed by cone-beam CT (CBCT), and to investigate its differential diagnosis, pathogenesis, and the application value of CBCT in the diagnosis of oral and maxillofacial diseases.Methods:One case of germinated teeth of the left mandibular second molar diagnosed according to oral general examination ad CBCT findings in Zhenjiang Stomatological Hospital, China in March, 2019 was included in this study. The characteristics and differential points of supernumerary cusp, fused teeth, geminated teeth and concresence of teeth were analyzed based on literatures.Results:CBCT examination showed that the number of mandibular dentition teeth was normal, there was a large area of low-density transmission area around the root of the left mandibular second molar. Three-dimensional reconstruction results revealed that the suspected supernumerary teeth were fused with the root of the left mandibular second molar. Sagittal projections showed that the suspected supernumerary teeth were located in the buccal side of the left mandibular second molar. Axial projections showed three separate root canal orifices at the level of pulp chamber floor, and the dentin of the two was connected. The suspected supernumerary teeth had an independent pulp cavity and a clear root canal, and fused with the distal root canal of the left mandibular second molar in the middle of the root to form a root canal. A "Y"-shaped structure was displayed on the sagittal projections. CBCT showed that the left mandibular second molar was a fused root. Based on oral clinical examination, the left mandibular second molar was confirmed to be a germinated tooth.Conclusion:CBCT is one of the most important means of oral auxiliary examination. It has significant advantages in the diagnosis of tooth abnormalities. It can help clinicians to make correct diagnosis and choose the appropriate treatment scheme. It has certain clinical significance and innovation.

ObjectiveTo investigate the risk factors for failure in emergency endoscopic injection sclerotherapy (EIS) combined with sequential histoacryl injection (HI) for esophagogastric variceal bleeding (EGVB) with portal vein embolus (PVE). MethodsA total of 109 EGVB patients with PVE who underwent emergency gastroscopy in Beijing Shijitan Hospital, Capital Medical University, and The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2019 were enrolled, and according to the outcome of hemostatic treatment under emergency gastroscopy, the patients were divided into hemostatic failure group with 28 patients and hemostatic success group with 81 patients. The two groups were compared in terms of general information, varices and bleeding manifestations under gastroscopy, blood biochemical parameters, Child-Pugh class, and Model for End-Stage Liver Disease (MELD) score, and the risk factors for hemostatic failure were analyzed. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; a logistic regression analysis was used for multivariate analysis. ResultsCompared with the hemostatic success group, the hemostatic failure group had significantly higher peripheral white blood cell count (WBC), total bilirubin (TBil), Child-Pugh class, and MELD score (Z=3.794, Z=4.751, χ2=40.104, Z=6.412, all P＜0001) and significantly lower prothrombin time activity (PTA), albumin (Alb), and cholinesterase (CHE) (t=9.653, Z=3.093, Z=4.092, P＜0.001, P=0.002, and P＜0.001). WBC (odds ratio ［OR］=28.543, 95% confidence interval ［CI］: 1.285-634.113, P＜0.05), PTA(OR=0.194, 95%CI: 0.045-0.835, P＜0.05), TBil (OR=2.197, 95%CI: 1.004-4.810, P＜0.05), Alb (OR=0448, 95%CI: 0.209-0.961, P＜0.05), and Child-Pugh class (OR=5.164, 95%CI: 1.307-20.406, P＜0.05) were independent risk factors for hemostatic failure. ConclusionWBC, PTA, TBil, Alb, and Child-Pugh class are independent risk factors for failure in emergency EIS combined with sequential HI in the treatment of EGVB with PVE, and adequate preoperative evaluation and correction may help to improve the success rate of hemostasis.

Objective To investigate the characteristics of activation-induced cytidine deaminase (AID) expression level in de novo acute leukemia (AL) patients, chronic myeloid leukemia chronic phase (CML-CP), chronic myeloid leukemia blastic crisis (CML-BC) patients and leukemia cell lines. Methods The expression level of AID mRNA was measured in 89 cases of newly-diagnosed acute lymphoblastic leukemia (ALL) patients, 79 cases of de novo acute myeloid leukemia (AML) patients, 5 cases of CML-BC patients, 5 cases of CML-CP patients and leukemia cell lines NB4, THP-1, KG-1, Raji, K562 by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), bone marrow mononuclear cells of 16 normal healthy donors were used as the control group. Results The expression levels of AID mRNA in 89 cases of ALL and 79 cases of AML were 0.006-7 463.175 and 0.005-69.107, the median expression levels were 3.785 and 1.812, the expression level of AID mRNA in the normal control group was 0.146-4.707, and the median expression level was 1.483, respectively. The AID expression levels of ALL, B-ALL, Burkitt leukemia, M4 patients and Raji cells were significantly higher than those of the normal control group (all P <0.05). Nevertheless, the AID mRNA expression levels of M3 patients and NB4, KG-1 cells were lower than those of the normal control group (all P <0.05). Furthermore, the AID mRNA expression levels of K562 cell were strikingly higher than that of the CML-CP patients (P<0.001), so were those of CML-BC, chronic myeloid leukemia myeloid blast crisis (CML-MBC), chronic myeloid leukemia lymphoblastic blast crisis (CML-LBC) patients. Conclusion AID gene shows high expression level in B-ALL, Burkitt leukemia and M4, low expression level in M3 and KG-1 cells, and obvious high expression level in CML-BC.

OBJECTIVE: To observe the short-term and long-term curative effect of the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer) application used in the 82 cases postoperative tissue shortage repair that after the head neck carcinoma resection. METHOD: To held the 82 cases head neck carcinoma postoperative mucosa shortage repaired after resection by the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer), 65 cases mucosa shortage wound be directly covered by the repair membrane and the other 17 cases mucosa shortage wound be repaired by the tranfered muscle tissue flap with the repair membrane covered; 53 cases underwent additional postoperative radiotherapy between 2-4 weeks and follow-up in 1, 3, 6, 12, 18, 24, 30, 36, 48, 60 months and observed the operation site repair process through the electronic laryngoscope, observed the patients respiration, swallow, phonation function. RESULT: Seventy-seven cases patients operation incision reached I phase healing standard, another 5 cases patients operation incision reached II phase healing standard because of the wound infection and fully-recovered through the local wound drainage,dressing process. All the patients tracheal cannula,the stomach tube be extubated successfully and without the local cicatricial constriction occurred. Seventy-eight cases follow up period reached 1 year including 53 cases who underwent postoperative radiotherapy, 49 cases follow up period reached 3 years including 32 cases who underwent postoperative radiotherapy, 14 cases follow up period reached 5 years including 12 cases who underwent postoperative radiotherapy. The patients with static local lesions discovered no reaction such as exclusion, allergy. CONCLUSION The application of xenogenic acellular dermal matrix membrane (or joint muscle flap transfer used in in the postoperative tissue shortage repair that after the head neck carcinoma resection have several advantage such as comparatively easily implementation, operation safety edge enough,well preserved organ function, comparatively low incidence about the laryngeal stenosis, the short-term and long-term repair effect are all exact.
Acellular Dermis ; Carcinoma, Squamous Cell ; radiotherapy ; surgery ; Female ; Head and Neck Neoplasms ; radiotherapy ; surgery ; Humans ; Male ; Mucous Membrane ; surgery ; Postoperative Period ; Squamous Cell Carcinoma of Head and Neck ; Surgical Flaps ; transplantation ; Wound Healing