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 clinical efficacy of Xuanfei Yipi Formula,a prescription derived from modified Jianpi Pill recorded in Yi Fang Ji Jie(A Collection of Prescriptions with Expositions),in treating senile sarcopenia with spleen-stomach weakness type,and to observe its effect on chronic low-grade inflammation of the patients.Methods Seventy cases of senile sarcopenia patients of spleen-stomach weakness type were randomly divided into an observation group and a control group,with 35 cases in each group.The control group was given exercise and nutritional guidance,while the observation group was treated with Xuanfei Yipi Formula orally on the basis of the control group,and the intervention time of both groups was eight weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,appendicular skeletal muscle mass index(ASMI),grip strength,6-meter walking pace,and the serum levels of C-reactive protein(CRP),interleukin 6(IL-6),tumor necrosis factor α(TNF-α)in the two groups before and after treatment were observed.After treatment,the clinical efficacy and safety of the patients in the two groups were evaluated.Results(1)After eight weeks of treatment,the total effective rate in the observation group was 94.29%(33/35),and that in the control group was 77.14%(27/35),the intergroup comparison(by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of TCM syndrome score in the observation group was more obviously than that in the control group(P＜0.01).(3)After eight weeks of treatment,the ASMI,grip strength and 6-meter walking pace in the two groups were significantly higher than those before treatment,and the increase of ASMI and grip strength in the observation group was more obviously than that in the control group(P＜0.05).(4)After eight weeks of treatment,the levels of serum CRP,IL-6,and TNF-α in the two groups were decreased significantly compared with those before treatment(P＜0.05),and the decrease of serum CRP level in the observation group was more obviously than that in the control group(P＜0.05).(5)During the treatment,no obvious adverse reactions occurred in both groups,and the safety indexes of liver and kidney functions of the patients were all within the normal range.Conclusion Xuanfei Yipi Formula can improve the clinical symptoms of senile sarcopenia patients,and its mechanism is probably related with the regulation of chronic low-grade inflammation.

Abdominal Wall/surgery* ; Adenocarcinoma, Clear Cell/surgery* ; Endometriosis/pathology* ; Humans

Objective: To observe the gadolinium imaging findings of inner ear in patients with sudden deafness and to analyze its clinical features. Methods: From November 2017 to July 2020, 21 patients with sudden deafness in the People's Hospital of Dongsheng District, Ordos City were selected as the research objects, including 14 males and 7 females, aged 36-76 years, with a median age of 50 years. The course of disease was 1-19 days, with an average of 5.5 days. The patients received audiology tests, laboratory examination, and intravenous gadolinium angiography, each of whom was scanned twice by 3D-FLAIR sequence: once before intravenous gadolinium injection, and once again 4.5-6.0 h after intravenous gadolinium injection. The following corresponding clinical treatment was given. The imaging manifestations and clinical features were observed. Results: Among 21 cases of sudden deafness in acute stage, the signal intensity of 11 cases was significantly higher than that of the contralateral ear, and 2 cases had vestibular labyrinthine hydrops. In laboratory examination, only 2 cases of total deafness had increased WBC count and faster erythrocyte sedimentation rate, and the rest had no abnormality. The hearing types of 21 patients with sudden deafness were: total deafness in 8 cases, flat decline in 10 cases, low frequency decline in 1 case, high frequency decline in 2 cases. The total effective rate was 57% (12/21). The hearing types of 11 patients with abnormal gadolinium angiography were total deafness in 5 cases, flat decline in 5 cases and high frequency decline in 1 case. The total effective rate was 64% (7/11). Conclusion: Gadolinium angiography is abnormal in some patients with sudden deafness, and the permeability of blood labyrinth barrier may be increased, which is worthy of further study.
Angiography ; Deafness ; Female ; Gadolinium ; Hearing Loss, Sudden/diagnostic imaging* ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Vestibule, Labyrinth

Cytokines are believed to be involved in a "vicious circle" of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose (30 μg/mL) iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.
Animals ; Apoptosis ; drug effects ; Bone Neoplasms ; complications ; drug therapy ; pathology ; secondary ; Bone Resorption ; complications ; drug therapy ; pathology ; Breast Neoplasms ; complications ; drug therapy ; genetics ; pathology ; Carcinogenesis ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Chromones ; administration & dosage ; Female ; Humans ; Interleukin-6 ; biosynthesis ; genetics ; MCF-7 Cells ; Neoplasm Invasiveness ; genetics ; pathology ; Rats ; Sulfonamides ; administration & dosage ; Transcription Factor RelA ; biosynthesis ; genetics

Shihu is one of the most valuable Chinese medicines in China. The sources of Shihu are complex and the quality evaluation of it mainly depends on morphologic characteristics distinction. In order to understand the Shihu's quality evaluation concept of Chinese herbalists in the past dynasties. This paper summarizes the methods of quality evaluation in ancient bencao systematically. The ancient bencao records that the quality of Shihu is closely related to its germplasm, habitat, processing and character. The concept of germplasm about shihu includes generalized and narrow sense, besides, the clinical applications of Dendrobium huoshanenese, D. officinale and D. nobile are focused on different diseases. D. huoshanenese has been regarded as Dao-di herbs since Qing Dynasty. The main products of Shihu contain fresh goods and dry goods, their clinical applications are also treated differently. Fengdou is one of the commodity specifications in Shihu. Its processing method probably dated from the Qing Dynasty, but now, it has become the mainstream commodityform. There was a common sense that different kinds of Shihu owed different characters and curative effects in ancient bencao, and the quality would enhance with the increasing viscidity. Therefore, the "Germplasm", "Geoherbs", "processing", "characters" were integrated into traditional quality evaluation methods of Shihu. Meanwhile, we should pay attention to the clinical efficacy of shihu with different species and processing methods.

PURPOSE: The association between Helicobacter pylori (H. pylori) and blood ammonia levels in cirrhotic patients is controversial. We aimed to clarify this controvercy by performing a meta-analysis of published studies. MATERIALS AND METHODS: We searched PubMed, EMBASE and Cochrane library for studies which explored the association between H. pylori and blood ammonia levels in cirrhotic patients before May 2012. Six cohort studies involved in 632 H. pylori positive and 396 H. pylori negative cirrhotic patients were eligible for our analysis. The summary estimates were presented as standard means differences (SMD) and 95% confidence intervals (CI) from individual studies. RESULTS: Overall, there was significant association between H. pylori infection and the elevated blood ammonia levels in cirrhotic patients (SMD=0.34, 95% CI=0.21-0.47, I2=42.1%). Sensitivity analysis further confirmed this association. Subgroup analysis showed that the association was found only in Asian ethnicity, but not in Caucasian ethnicity. CONCLUSION: H. pylori infection is associated with elevated blood ammonia levels in cirrhotic patients, and more large scale studies and stratify analysis are warranted in order to further evaluate this association.
Ammonia/blood ; Asian Continental Ancestry Group ; European Continental Ancestry Group ; Helicobacter Infections/*blood ; Helicobacter pylori/pathogenicity ; Humans ; Liver Cirrhosis/*blood/*microbiology ; Publication Bias ; Regression Analysis

Objective To investigate the mechanical properties of Ni-Ti wires with direct electric resistance heat treatment(DERHT) method in three-point bending tests. Methods Two superelastic Ni-Ti wires(wire A: Smart SE, wire B: SENTALLOY SE, 0.406 mm ×0.559 mm) and 2 heat-actived Ni-Ti wires(wire C: Smart SM, wire D: L&H TITAN, 0.406 mm ×0.559 mm) were selected. They were heattreated using the DERHT method by a controlled electric current(6. 36 A) applied for different period of time[0(control), 1.0, 1.5, 2. 0, 2. 5 seconds). Then, a three-point bending test was performed under controlled temperature (37 ℃ ) to examine the relationships between the deflection and the load in the bending of wires. Results After DERHT treatment, the plateau in the force-deflection curve of superelastic Ni-Ti wires and heat-actived Ni-Ti wires were increased. When the wires were heated for 2. 0 seconds and deflected to 1.5 mm, the loading force of A, B, C and D Ni-Ti wires increased from (3.85 ± 0. 11 ),(3.62±0.07), (3.28±0.09), (2.91 ±0.23) Nto (4.33 ±0.07), (4.07 ±0.05), (4.52±0.08),(3.27 ± 0. 15 ) N respectively. Conclusions DERHT method is very convenient for clinical use. It is possible to change the arch form and superelastic force of NiTi wires. The longer the heating time is, the more the superelastic characteristics of the wires are altered.

OBJECTIVETo investigate the impairment pattern and the influencing factors of pulmonary function in patients with Marfan and Marfanoid syndrome associated scoliosis (MS).

METHODSIn this retrospective study, totally 25 MS patients (aged 11 - 20 years, 11 boys and 14 girls) who received posterior instrumentation and fusion (Group A) and 38 adolescent idiopathic scoliosis (AIS) patients (Group B) (aged 10 - 19 years, 11 boys and 27 girls) were included from February 1998 to September 2007. The curve pattern was matched in both groups. The preoperative pulmonary function test (PFTs) were compared in two groups. And the parameters influencing the preoperative pulmonary function were analyzed in group A.

RESULTSIn Group A, the Cobb angle of thoracic curve was negatively correlated with the percentage of predicted pulmonary volumes (VC%, FVC% and FEV1%) (r = -0.514, -0.503, -0.464, P < 0.05). And the reduction of lung function parameters (VC%, FVC%, FEV1% and MMEF%) was more severe in Group A than in Group B with compared magnitude of thoracic curve (P < 0.05). In Group A, the extent of impairment of pulmonary function in patients with the number of vertebrae involved ≥ 8 were more severe than those involved < 8 vertebrae (P < 0.05). However, there was no significant difference of deterioration of lung function between the higher apex (T₄₋₈) subgroup and lower apex (T₉₋₁₂) subgroup. And no correlation was found between thoracic kyphosis and the degrees of impairment of respiration function.

CONCLUSIONSPatients with MS have mixed ventilation dysfunction, which is more severe than AIS patients with matched age and Cobb angle. The pulmonary dysfunction in MS patients can be influenced by the severity of thoracic curve and the number of involved vertebrae.

Adolescent ; Child ; Female ; Humans ; Lung ; physiopathology ; Male ; Marfan Syndrome ; complications ; physiopathology ; Respiratory Function Tests ; Retrospective Studies ; Scoliosis ; complications ; physiopathology ; Young Adult

Objective To investigate the relationship between condyle movement and temporomandibular disorders(TMD)in patients with Class Ⅱ division 1 malocclusion.Methods Twenty patients(from 11 to 12 years old)with Class Ⅱ division 1 malocclusion before treatment were collected.Computer aided diagnosis axiograph(CADIAX)and magnetic resonance images(MRI)were used to analyze the condyle movement between disc displacement and normal groups.Results The sensitive values were found in open/close process in patients with disc displacement:Y[Left:(0.32±0.10)mm,Right:(-0.91±0.49)mm],Z[Left:(4.20±0.70)mm,Right:(3.44±0.21)mm],sagittal condylar inclination(SCI)[Left:(32.48±7.70)°,Risht:(33.47±12.60)°]and horizontal condylar inclination (TCI)[Left:(-2.60±2.02)°,R:(-9.23±5.58)°],and those items showed significant difference between two groups.Conclusions The side shift of condyle movement in maximum open/close process might be the inducement of disc displacement.It was revealed that the changes in condyle movement could give useful information in early stage of functional treatment.