1.Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.
Yue ZHANG ; Jingwen GAO ; Na LI ; Peng XU ; Shimeng QU ; Jinqian CHENG ; Mingrui WANG ; Xueru LI ; Yaheng SONG ; Fan XIAO ; Xinyu YANG ; Jihong LIU ; Hao HONG ; Ronghao MU ; Xiaotian LI ; Youmei WANG ; Hui XU ; Yuan XIE ; Tianming GAO ; Guangji WANG ; Jiye AA
Acta Pharmaceutica Sinica B 2024;14(2):667-681
Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.
2.Clinical and genetic analysis of two children with TANC2 gene variants and a literature review
Manman CHU ; Dan XU ; Jiayang XIE ; Xiaoli ZHANG ; Mengyue WANG ; Jialin LI ; Yichao MA ; Xiaoli LI ; Junling WANG ; Tianming JIA
Chinese Journal of Medical Genetics 2024;41(10):1195-1200
Objective:To explore the clinical and genetic characteristics of two children with Neurodevelopmental disorders (NDDs) due to variants of TANC2 gene. Methods:Clinical data of two children who were admitted to the Third Affiliated Hospital of Zhengzhou University respectively in April 2020 and April 2021 were retrospectively analyzed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. By using " TANC2 gene", "Neurodevelopmental disorders", "Nervous system development disorders", " TANC2" as the key words, similar cases were searched from the CNKI, Wanfang database platform and PubMed database, with the search time set as from the establishment of the database to December 2023. This study was approved by Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No. 2020-57). Results:Case 1 was a 1-year-and-3-month-old girl who had developed convulsions at 1 year old and had three episodes of seizures. Her epilepsy had resolved with the treatment of oxcarbazepine, which was stopped at the age of 2-year-and-7-month. Her language, movement and intelligence development were all normal. Case 2 was a 1-year-and-10-month-old boy, who had developed convulsions at 1 year old. His seizure type was myoclonus, and the frequency was dozens of times a day. His epilepsy had resolved with the treatment of sodium valproate. His language, movement and intelligence development was delayed for about half a year. Genetic analysis showed that both children had harbored novel variants of the TANC2 gene (NM_025185.4), including c. 3398G>A (p.Gly1133Glu) and c.2829+ 1G>A, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the former was rated as likely pathogenic (PS2+ PM2_Supporting+ PP3) and the latter was rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Two previous reports were retrieved, which had involved 17 cases and 16 variants. Common features had included autism spectrum disorder (70.6%, 12/17), intellectual disability (94.1%, 16/17), language and motor retardation (88.2%, 15/17; 58.8%, 10/17), facial dysmorphism, epilepsy, ataxia, and thoracic and spinal deformities. Conclusion:Variants of the TANC2 gene probably underlay the epilepsy and development delay in these children with NDDs.
3.Androgenic granulosa cell tumor of ovary: a case report and literature review
Xiaoyu HE ; Xi CHEN ; Tianming XIE ; Junhui XIE
Chinese Journal of Endocrinology and Metabolism 2023;39(12):1080-1082
This article reports a case of oligomenorrhea accompanied by acne over several years. The patient presented with hyperandrogenism and insulin resistance. The initial diagnosis considered polycystic ovary syndrome(PCOS) and was treated with oral medication for 2 months, with no significant improvement. Further ultrasound examination revealed a right ovarian heterogeneous mass (3.2 cm×3.0 cm). The patient underwent laparoscopic resection of the right ovarian lesion. Postoperative pathology revealed ovarian sex cord-stromal cell tumor, adult granulosa cell tumor(diffuse type). Testosterone levels decreased to the normal 3 days after the surgery, and menstruation resumed within 2 months. This article summarizes the presented case and reviews the relevant literature. For women with severe hyperandrogenism and masculinization, it is recommended to thoroughly assess the possibility of androgen-secreting tumors.
4.A Glassy Carbon Electrode Modified with Electrochemically Reduced Graphene Oxide/Gold Nanoparticles-Chitosan Composite Film for Sensitive Determination of Uric Acid
Ling WU ; Zhong CAO ; Tianming SONG ; Cheng SONG ; Jinglei XIE ; Jinglin HE ; Zhongliang XIAO
Chinese Journal of Analytical Chemistry 2014;(11):1656-1660
Anelectrochemicallyreducedgrapheneoxide/goldnanoparticle-chitosan(ERGO/AuNP-CS) composite film modified glassy carbon electrode ( GCE) was constructed by directly electrochemical reduction of GO, and then assembly of AuNP-CS polycation on the surface. The surface morphologies of different modified electrodes including bare GCE, GCE/GO, GCE/ERGO and GCE/ERGO/AuNP-CS were characterized by scanning electron microscopy ( SEM ) . The differential pulse voltammetric behaviors of the electrodes were investigated, and the results indicated that the composite of ERGO/AuNP-CS exhibited excellent electrocatalytic oxidation activity to uric acid ( UA) molecule. In 0. 10 mol/L of phosphate buffer solution (pH=6. 5) with a scanning rate of 100 mV/s, the proposed composite film modified electrode showed a linear electrochemical response to UA in the range of 0 . 05-110 μmol/L with a detection limit of 12. 4 nmol/L ( S/N = 3 ). The electrode displayed good selectivity, reproducibility and stability in the determination of UA in human serum and urine samples with a recovery of 93 . 8%-104 . 1%. The detection results were agreed with those of conventional spectrophotometry and uricase Kit methods.
5.Safety and feasibility of fast track surgery in operations for gastric cancer: a meta analysis
Junlan YANG ; Mancai WANG ; Xiaofeng XIE ; Bodong WEI ; Tianming GAO ; Yinping ZHANG
Chinese Journal of Digestive Surgery 2012;11(5):455-461
Objective To estimate the safety and feasibility of fast track surgery (FTS) in operations for gastric cancer.Methods The Cochrane library,PubMed,EMBASE,Chinese biomedical literature database,China journal full text database,Chinese scientific journals full text database were searched with the key words of gastric cancer,gastric carcinoma, FTS,fast track surgery, enhanced recovery after surgery,ERAS, 胃癌,and 快速康复外科.The search was finished in April,2011.Randomized controlled trials of FTS for patients with gastric cancer were included.Two reviewers evaluated the quality of the included studies and extracted the data independently.Meta analysis was performed by RevMan 5.1.2 software.Results Fourteen randomized controlled trials involving 1270 patients were included.The results of meta analysis showed that FTS could significantly shorten the first exhaust time (MD =-6.15,95 % confidence interval:-8.22- -4.07,P< 0.05) and hospital stay ( MD =- 2.68,95% confidence interval:- 3.26- - 2.10,P < 0.05 ),and reduced the hospital fees ( MD =- 0.39,95 % confidence interval:- 0.55- - 0.22,P < 0.05 ).FTS could lighten the postoperative stress and relatively enhance the immunity.Conclusion Compared with conventional methods,FTS could speed up the rehabilitation for patients with gastric cancer postoperatively without increasing the adverse reactions.

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