1.Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.
Wanyu TANG ; Zhixue MA ; Bang LI ; Zhexiang YU ; Xiaobao ZHAO ; Huicui YANG ; Jian HU ; Sheng TIAN ; Linghan GU ; Jiaojiao CHEN ; Xing ZOU ; Qi WANG ; Fan CHEN ; Guangying LI ; Chaonan ZHENG ; Shuliu GAO ; Wenjing LIU ; Yue LI ; Wenhua ZHENG ; Mingmei WANG ; Na YE ; Xuechu ZHEN
Acta Pharmaceutica Sinica B 2025;15(10):5346-5365
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.
2.Review of chemical composition, pharmacological effects, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma and prediction of its Q-markers.
Xiao-Xiao SHAN ; Bang-Zhen HONG ; Jie LIU ; Guo-Kai WANG ; Wei-Dong CHEN ; Nian-Jun YU ; Dai-Yin PENG ; Lei WANG ; Cai-Yun ZHANG
China Journal of Chinese Materia Medica 2021;46(21):5496-5511
Salviae Miltiorrhizae Radix et Rhizoma is a Chinese herbal medicine that promotes blood circulation to remove blood stasis, nourishes blood to tranquilize the mind, and cools blood to disperse carbuncles. Salviae Miltiorrhizae Radix et Rhizoma has microcirculation-improving, blood vessel-dilating, atherosclerosis-preventing, anti-inflammatory, anti-tumor, and blood pressure-and blood lipid-lowering activities. As research progresses, the chemical composition, pharmacological effect, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma have attracted much attention. We reviewed the research progress in this field. Based on the concept of quality marker(Q-marker) in traditional Chinese medicine, the Q-markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted and analyzed from the aspects of quality transfer, traceability, ingredient specificity, association between ingredients and pharmacological effects, ingredient predictability, and compounding environment. This review provides a scientific basis for the quality control of Salviae Miltiorrhizae Radix et Rhizoma and its preparations.
Drugs, Chinese Herbal/pharmacology*
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Medicine, Chinese Traditional
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Plant Roots
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Rhizome
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Salvia miltiorrhiza
3.Dynamic Changes of Trace Elements in Yu Salvia miltiorrhiza in Different Growth Periods
Qin-rong LIU ; Yi-shuo WANG ; Yong-sheng JI ; Zhen-ling ZHANG ; Yan-bang SHI ; Li-na ZHAO ; Yu-quan WU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(12):177-184
Objective:To establish an atomic absorption spectrometry to determine the content of eight trace elements of Yu
4.Comparison of sagittal plane morphology of spine and pelvis in adolescents with L₅S₁ developmental spondylolisthesis and isthmic spondylolisthesis.
Zi-Hui LI ; Xi CHEN ; Xu SUN ; Bin WANG ; Ze-Zhang ZHU ; Bang-Ping QIAN ; Zhen LIU ; Yang YU ; Yong QIU
China Journal of Orthopaedics and Traumatology 2019;32(3):234-238
OBJECTIVE:
To compare the sagittal morphological features of the spine and pelvis between L₅S₁ dysplastic spondylolisthesis and isthmus spondylolisthesis in adolescent.
METHODS:
Retrospective analysis of 24 cases of adolescent L₅S₁ spondylolisthesis with complete imaging data from May 2002 to December 2016. Those included 8 males and 16 females, aged from 10 to 18 years old with an average of (13.4±2.0) years. Among them, 9 cases were diagnosed as dysplastic spondylolisthesis (dysplasia group) and 15 cases isthmic spondylolisthesis (ischemic group). Radiographic parameters including slippage distance, slippage degree, slippage angle, sagittal vertical axis(SVA), thoracic kyphosis(TK), lumbar lordosis(LL), L₅ incidence(L₅I), pelvic incidence(PI), pelvic tilt(PT), sacral slope(SS), sagittal pelvic thickness(SPT), lumbosacral angle (LSA), sacral table angle (STA) were measured on the spinal lateral X-ray of the standing position. Independent-samples t-test was used in the comparison of each variable between two groups. <0.05 was considered statistically significant.
RESULTS:
There were no significant differences in slippage distance, slippage rate, slippage angle between two groups. In dysplasia group, SVA, L₅I, PT, SPT were (37.0±48.4) mm, (57.0±14.8)°, (42.3±15.4)°, (56.1±21.2) mm, respectively, and (-11.0±22.2) mm, (31.7±19.3) °, ( 15.5±10.2)°, (31.4±19.1) mm in ischemic group; and the differences between the two groups were significant(<0.05). In ischemic group, SS, LSA, STA were (44.1±12.6)°, (103.9±21.7)°, (92.7±9.9)°, respectively, and (25.9±20.2) °, (75.4±16.4) °, (75.4±9.7) ° in dysplasia group; and the differences between the two groups were significant(<0.05). There was no significant difference in TK, LL between two groups(>0.05).
CONCLUSIONS
Significant different from isthmic spondylolisthesis, adolescents with dysplastic spondylolisthesis present a different spino-pelvic sagittal alignment, characterized with trunk forward leaning and pelvic retroversion. In case of sagittal imbalance, early surgical intervention is required to restore a balanced spino-pelvic alignment.
Adolescent
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Child
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Female
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Humans
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Lumbar Vertebrae
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Male
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Pelvis
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Postural Balance
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Radiography
;
Retrospective Studies
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Spine
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Spondylolisthesis
;
surgery
5.Application of Digital Image Processing Technology in Scanning Electrochemical Microscope
Wei WANG ; Zhen-Bang LIU ; Yu BAO ; Yi-Ran GUAN ; Li NIU ; Guo-Yu ZHANG
Chinese Journal of Analytical Chemistry 2018;46(3):342-347
Ultramicroelectrode was usually used in scanning electrochemical microscope(SECM) as a probe. The redox reaction on the probe is a diffusion process. But the fast moving of probe in SECM will affect the diffusion process, resulting in unclear obtained images. A new SECM image-processing technique was proposed in this paper involving combination of LoG algorithm and New edge-directed interpolation (NEDI) interpolation algorithm. LoG algorithm is helpful for the clarity of SECM images, but leading to some loss of edge information. Fortunately, NEDI algorithm based on edge directed interpolation can solve this problem well. Two substrates with gold interdigitated electrode and gold electrode array were prepared by ion sputtering method. The SECM images were obtained of the gold interdigitated electrode, gold electrode array and ITO substrate printed with fingerprints. The corresponding images treated by LoG filter and these for NEDI interpolation were compared and analyzed. The image-processing technique combining the LoG algorithm with the NEDI interpolation algorithm can significantly improve the clarity and resolution of SECM image.
6.Arthroscopic patelloplasty and circumpatellar denervation for the treatment of patellofemoral osteoarthritis.
Gang ZHA ; Yu-jie LIU ; Bang-tuo YUAN ; Xue-zhen SHEN ; Feng QU ; Jiang-tao WANG ; Wei QI ; Juan-li ZHU ; Yang LIU
China Journal of Orthopaedics and Traumatology 2015;28(6):542-546
OBJECTIVETo investigate surgical procedure and clinical effects for the treatment of patellofemoral osteoarthritis (PFOA) with arthroscopic patelloplasty and circumpatellar denervation.
METHODSTotally 156 patients with PFOA (62 males and 94 females; aged from 45 to 61 years old with an average of 52) were treated from September 2011 and March 2013. The clinical manifestations included recurrent swelling and pains on knee-joint,and aggravated pains upon going up/down-stairs, squatting-down, or standing-up. PFOAs were treated with arthroscopic patelloplasty and circumpatellar denervation. The therapeutic effects before and after surgery were evaluated by Lysholm scores and Kujala scores. The therapeutic effects were graded by classification of cartilage injury degrees.
RESULTSTotally 149 cases were successfully followed up for 14.8 months. The incisions were healed well and no complication were occurred. Lysholm score was improved from 73.29 preoperatively to 80.93 postoperatively and average Kajala score from 68.34 preoperatively to 76.48 after surgery. This procedure was highly effective for patients with I - III degree cartilage injury, while not for patients with IV degree cartilage injury.
CONCLUSIONFor PFOA patients, arthroscopic patelloplasty and circumpatellar denervation is effective for significantly relieving anterior knee pains, improving knee-joint functions and quality of life, and deferring arthritic procession.
Arthroscopy ; Denervation ; Female ; Humans ; Knee Joint ; innervation ; surgery ; Male ; Middle Aged ; Osteoarthritis, Knee ; physiopathology ; surgery ; Range of Motion, Articular ; Treatment Outcome
7.Hamstring tendon transplantation embedding reconstruction of medial patellofemoral ligament for the treatment of recurrent patellar dislocation.
Gang ZHAO ; Yu-jie LIU ; Jun-liang WANG ; Wei QI ; Feng QU ; Bang-tuo YUAN ; Jiang-tao WANG ; Xue-zhen SHEN ; Yang LIU ; Juan-li ZHU
China Journal of Orthopaedics and Traumatology 2015;28(2):141-144
OBJECTIVETo explore the effectiveness of hamstring tendon graft embedding reconstruction of medial patellofemoral ligament for the treatment of recurrent dislocation of the patella.
METHODSFrom March 2008 to June 2013,67 patients with recurrent dislocation of patella were treated, including 28 males, 39 females with an average age of 22 years ranging from 10 to 42 years old. The clinical manifestations involved knee joint instability,"giving way", sense of patellar dislocation, anterior knee pain. All 67 patients underwent arthroscopic hamstring tendon graft embedding reconstruction of the medial patellofemoral ligament. The curative effect were evaluated by preoperative and postoperative Lysholm score and Q angle changes.
RESULTSAll cases were followed up after operation and the mean follow-up time was(27.5±13.4) months(4 to 69 months). Postoperative incision were healed well and no patellar dislocation or subluxation occurred. Lysholm score improved from preoperative 76.35±2.86 to 82.71±2.29 postoperatively; Q angle decreased from preoperative (18.75±2.33)° to postoperative(13.28±1.75)°.
CONCLUSIONThe method for the reconstruction of medial patellofemoral ligament can provide enough tension, patellar stability.imoroving the function of knee ioint.
Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Patellar Dislocation ; surgery ; Patellar Ligament ; surgery ; Patellofemoral Joint ; surgery ; Reconstructive Surgical Procedures ; methods ; Recurrence ; Tendons ; transplantation
8.A rare case of intratesticular leiomyoma.
Zhan Peng YONG ; Zhen Bang LIU ; Cora CHAU ; Kian Tai CHONG
Singapore medical journal 2015;56(9):e145-6
A 47-year-old man presented with a scrotal swelling. Ultrasonography of the testes showed that it was an extratesticular swelling. However, the swelling was intraoperatively found to be intratesticular. Histology showed an intratesticular leiomyoma, which is extremely rare.
Diagnosis, Differential
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Humans
;
Leiomyoma
;
diagnosis
;
diagnostic imaging
;
surgery
;
Male
;
Middle Aged
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Scrotum
;
pathology
;
Testicular Neoplasms
;
diagnosis
;
diagnostic imaging
;
surgery
;
Treatment Outcome
;
Ultrasonography
9.Arthroscopic surgery for the treatment of the synovial chondroma of subacromial bursa: two cases report and review.
Bang-Tuo YUAN ; Feng QU ; Jiang-Tao WANG ; Xue-Zhen SHEN ; Gang ZHAO ; Yang LIU ; Juan-Li ZHU ; Yu-Jie LIU
China Journal of Orthopaedics and Traumatology 2014;27(6):482-485
Adult
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Arthroscopy
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Bursa, Synovial
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surgery
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Chondroma
;
surgery
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Female
;
Humans
;
Middle Aged
10.Etiological analysis and significance of anterior knee pain induced by gluteal muscles contracture.
Gang ZHAO ; Yu-jie LIU ; Jun-liang WANG ; Wei QI ; Feng QU ; Bang-tuo YUAN ; Jiang-tao WANG ; Xue-zhen SHEN ; Yang LIU ; Juan-li ZHU
China Journal of Orthopaedics and Traumatology 2014;27(12):1000-1002
OBJECTIVETo explore causes of gluteal muscle contracture induced anterior knee pain and curative effect of arthroscopic release.
METHODSFrom March 2002 to August 2013,36 patients with gluteal muscle contracture induced anterior knee pain were treated, including 15 males, 21 females, aged from 9 to 40 years old with an average (18.7±7.2) years old; the courses of diseases ranged from 4 to 30 years. The clinical manifestations involved limited to symmelia, positive Ober sign, buttocks touch contracture belts, knee and patella slide to lateral when doing squat activities. All patients were performed gluteal muscle contracture release under arthroscopic. Postoperative complications were observed, Kujala scoring before and after operation was used for compare curative effect.
RESULTSAll patients were followed up with an average of 29 months. The incision were healed well, and no complications were occurred. Postoperative Kujala score were improved more than preoperative.
CONCLUSIONGluteal muscle contracture release could alleviate hypertension of lateral patella, and palys an important role in preventing patellofemoral arthritis.
Adolescent ; Adult ; Buttocks ; Child ; Contracture ; physiopathology ; Female ; Humans ; Knee ; Male ; Pain ; etiology

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