1.Advances in the Application of Repetitive Transcranial Magnetic Stimulation for Acute and Maintenance Treatment of Major Depressive Disorder
Medical Journal of Peking Union Medical College Hospital 2025;16(2):321-329
Major depressive disorder (MDD) is a prevalent psychiatric condition characterized by high rates of prevalence and recurrence. Repetitive transcranial magnetic stimulation (rTMS) has been widely utilized in the acute phase treatment of MDD and has shown potential in maintenance therapy. However, the factors influencing the efficacy of rTMS during the acute phase and the sustainability of its long-term therapeutic effects remain incompletely understood. Additionally, a consensus on the optimal maintenance treatment protocol has yet to be established. This article reviews recent evidence on the application of rTMS in both acute and maintenance treatment of MDD, aiming to summarize current research progress and provide insights for the further promotion and application of rTMS in clinical practice.
2.Protective Effect of Bushen Zhuyun Prescription on Abortion Rats with Kidney Deficiency-Corpus Luteum Inhibition Syndrome via ERα/PI3K/Akt Signaling Pathwa
Changyue SONG ; Siyu LI ; Fengyu HUANG ; Mingzhu QI ; Daiyue DING ; Shuangfei DENG ; Heqiao LI ; Jinghong XIE ; Guohua WANG ; Chen ZANG ; Hong XU ; Xiaohui SU ; Xiangying KONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):107-116
ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription (BSZY) on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group (Control), a model group (Model), low-dose BSZY (BSZY-L), medium-dose BSZY (BSZY-M), and high-dose BSZY (BSZY-H) groups (2.57, 5.14, 10.28 g·kg-¹), and a Zishen Yutai Pill (ZSYT) group (1.575 g·kg-¹). Hematoxylin-eosin (HE) staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was employed to measure levels of estrogen (E₂), progesterone (P), luteinizing hormone (LH), prolactin (PRL), and follicle-stimulating hormone (FSH) in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 databases, while disease targets for recurrent spontaneous abortion (RSA) were retrieved from GeneCards, DrugBank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor (ERα), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) and explore its protective mechanism on RSA rats. ResultsCompared with the control group, the model group exhibited significantly decreased uterine, ovarian, and embryonic wet weights (P<0.05, P<0.01), with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles, primary follicles, mature follicles, and corpora lutea, along with a large number of atretic follicles. The endometrium was thinner, and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast, compared with the model group, the BSZY groups at all doses and the ZSYT group demonstrated increased uterine, ovarian, and embryonic wet weights, along with a reduced abortion rate. The number of primordial follicles, primary follicles, mature follicles, and corpora lutea increased, while atretic follicles decreased. The endometrium thickened, and decidual tissue displayed normal cellular structure with tight arrangement. Additionally, the model group showed significantly decreased levels of E₂, P, PRL, and FSH in serum (P<0.05, P<0.01), along with a decreasing trend in LH level. In contrast, the BSZY groups at all doses exhibited significantly elevated levels of E₂, P, LH, PRL, and FSH in serum (P<0.05, P<0.01). Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα, PI3K, and p-Akt proteins (P<0.05, P<0.01). ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome, possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function, thereby lowering the abortion rate.
3.Divergent activation patterns of BRS3 revealed by two Chinese herb-derived agonists.
Jie LI ; Changyao LI ; Qingtong ZHOU ; Wei HAN ; Mingzhu FANG ; Youwei XU ; Yiting MAI ; Yao ZHANG ; Jiahua CUI ; H Eric XU ; Yan ZHANG ; Wanchao YIN ; Ming-Wei WANG
Acta Pharmaceutica Sinica B 2025;15(10):5231-5243
Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-Gq complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.
4.Post-embolization syndrome occurring after transhepatic arterial chemoembolization:analysis of its related factors
Mingzhu GAO ; Kewu HE ; Guangjing GUO ; Lili LI
Journal of Interventional Radiology 2024;33(11):1225-1228
Objective To analyze the factors influencing the occurrence of post-embolization syndrome(PES)after transhepatic arterial chemoembolization(TACE).Methods A total of 107 patients with hepatocellular carcinoma(HCC),who received TACE treatment at authors'hospital between February 2021 and March 2023,were included in the study.Among them,56 patients developed PES(PES group)and 51 patients did not develop PES(non-PES group).The demographic data,medical history,pathological findings,laboratory indicators and operation-related materials were compared between the two groups,and the risk factors for PES were analyzed.Results There were statistically significant differences in tumor diameter,albumin(ALB)level,preoperative physical condition(ECOG)score,type of embolization agent,drug-loaded microspheres,number of microspheres,and dosage of loaded drug between the two groups(all P<0.05).Multivariate Logistic analysis revealed that drug-loaded microspheres,number of microspheres,and dosage of loaded drug were the independent risk factors for PES occurring after TACE(all P<0.05).Conclusion HCC patients treated with TACE using drug-loaded microspheres,large amount of microspheres and high dosage of loaded drug have a higher risk of PES occurring after TACE.For patients having the above risk factors,the formulation of corresponding perioperative intervention strategies is necessary so as to avoid the occurrence of PES and to improve the safety of TACE.
5.Repair methods and effects of refractory wounds in patients after spinal internal fixation operation
Lili LI ; Wenchang YU ; Bo LI ; Deyong WU ; Jinyong WANG ; Xiaohui ZOU ; Mingzhu WANG ; Xiangrong XU
Chinese Journal of Burns 2024;40(6):529-535
Objective:To explore the repair methods and effects of refractory wounds in patients after spinal internal fixation operation .Methods:The study was a retrospective observational study. From November 2020 to October 2023, 10 patients with refractory wounds after spinal internal fixation operation were admitted to the Department of Burns and Plastic Surgery of Changde Hospital of Xiangya School of Medicine of Central South University. They were 3 males and 7 females, aged 35 to 68 years. There were 6 cases of thoracolumbar tuberculosis, 3 cases of thoracolumbar fracture, and 1 case of recurrent sacrococcygeal chordoma with skin, soft tissue, and bone defects after radical resection. The wound areas after debridement were 6.0 cm×1.5 cm to 27.0 cm×6.5 cm. The wound repair operation was decided to perform in the primary stage or in the secondary stage according to the wound situation. Two patients with type Ⅰ wounds were treated with debridement, direct suture, and continuous irrigation and drainage with catheter after operation. Eight patients with type Ⅱ wounds were repaired with local flaps (including rotation flap with dermis-fat flap at the end), muscle flaps, or muscle flaps combined with local flaps. The flap sizes were 10.0 cm×5.0 cm to 27.0 cm×14.0 cm, and the sizes of muscle flap were 8.0 cm×5.0 cm×4.0 cm to 17.0 cm×9.5 cm×2.0 cm. The wounds in flap donor areas were sutured directly. The wound treatment methods of patients with type Ⅱ wounds were recorded. The wound healing was observed after operation. The infection and recurrence of wounds, the retention of internal fixation materials, and spinal motor function were observed during follow-up.Results:Among patients with type Ⅱ wounds, there were 3 cases applied with local flaps (including 1 case with rotation flap with dermis-fat flap at the end), 3 cases with muscle flaps (including 1 case with latissimus dorsi muscle flap and 2 cases with erector spinal muscle flaps), and 2 cases with muscle flaps (1 case with latissimus dorsi muscle flap and 1 case with erector spinal muscle flap) combined with local flaps. Only 1 case with secondary defects after radical surgery of sacrococcygeal chordoma had poor wound healing which healed after dressing change, and the wounds of the remaining 9 cases all healed well. During the follow-up of 4 to 18 months, no infection or recurrence of local wounds developed in 10 patients, the internal fixation materials were not loosening, and there was no significant limitation in spinal motor function.Conclusions:For refractory wounds after spinal internal fixation operation, according to the wound type of patients, debridement, suture, irrigation, and drainage in the primary stage, or transplantation of local flaps, muscle flaps, muscle flaps combined with local flaps are performed in the primary stage or in the secondary stage. These methods are proved to have reliable therapeutic effects, not only repairing the wounds, but also retaining the internal fixation materials.
6.Reference range and impact factors of left ventricular trabecular and papillary muscle mass in Chinese adults explored by cardiac MRI
Gengxiao LI ; Zhen ZHANG ; Shanshan ZHOU ; Jianan XIE ; Yiyuan GAO ; Shurong LIU ; Zhiwei ZHAO ; Jun ZHAO ; Mingzhu ZHANG ; Kai SUN ; Kuncheng LI
Journal of Practical Radiology 2024;40(2):209-212
Objective To establish normal reference values for left ventricular trabecular and papillary muscle mass(TPMM)in Chinese adults using MRI and to explore its impact factors.Methods A total of 168 healthy Chinese adults were retrospectively included,and compacted and total left ventricular myocardial mass(LVM)were measured using traditional and dedicated methods,respectively.TPMM was calculated from the difference between total and compacted LVM.Independent sample t-tests and analysis of variance were used to explore the differences in TPMM among genders and age groups,while multiple linear regression was used to explore the independent correlation between TPMM and age,gender,heart rate,systolic blood pressure(SBP),fasting blood glucose(FBG),and body mass index(BMI).Results TPMM for men was significantly larger than that for female(P<0.001).TPMM in the elderly group was significantly larger in female(P<0.05),but not in men.Multiple linear regression showed that BMI and SBP were both independently positively correlated with TPMM,and female and heart rate were independently negatively correlated with TPMM(P<0.05).Conclusion This study provides age-and gender-specific normal reference values for TPMM in Chinese adults.Gender,heart rate,BMI,and SBP are all independently associated with TPMM.
7.Diagnostic value of ultra-wide field swept-source optical coherence tomo-graphy angiography combined with ultra-wide field scanning laser ophthal-moscopy in diabetic retinopathy
Mingzhu MAO ; Mengyu LI ; Dingyang WEI ; Li CHEN ; Yi LIU ; Jie LI ; Jie ZHONG
Recent Advances in Ophthalmology 2024;44(4):291-296
Objective To investigate the detection rate and grading diagnostic value of ultra-wide field swept-source optical coherence tomography angiography(UWF SS-OCTA)combined with ultra-wide field scanning laser ophthalmoscopy(UWF SLO)in diabetic retinopathy(DR)lesions.Methods In this cross-sectional study,diabetic patients attending the Ophthalmology Department of Sichuan Provincial Peoples Hospital were recruited.All participants underwent UWF SS-OC-TA,UWF SLO and fundus fluorescein angiography to detect DR lesions,including microaneurysms(MA),intraretinal hem-orrhages(IRH),nonperfusion areas(NPAs),intraretinal microvascular abnormalities(IRMAs),venous beading(VB),neovascularization elsewhere(NVE),neovascularization of the optic disc(NVD),and vitreous hemorrhage(VH).The re-sults of the combination of three imaging examinations(triple imaging)were used as the standards,evaluating the detec-tion rate and severity grading consistency in DR lesions of pairwise combinations of different imaging modalities.Results A total of 101 patients(175 eyes)were included.Compared with the triple imaging results,the detection rates of UWF SS-OCTA combined with UWF SLO for MA,IRH,NPAs,IRMAs,NVE,NVD and VH were 91%,83%,77%,69%,27%,10%and 12%,respectively,with Kappa values of 0.812,1.000,1.000,1.000,0.986,0.970 and 1.000.Compared with the triple imaging results,the combination of UWF SS-OCTA and UWF SLO demonstrated excellent consistency in grading the severity of DR(Kappa=0.943).Conclusion UWF SS-OCTA combined with UWF SLO can accurately identify MA,IRH,NPAs,IRMAs,NVE,NVD and VH,demonstrating high accuracy in DR screening and grading diagnosis,making it suitable for large-scale screening and management of DR in clinical practice.
8.Research progress of active components and compounds of traditional Chinese medicine improving liver fibrosis by regulating JAK/STAT signaling pathway
Siming DENG ; Lijian LIU ; Liqun LI ; Chengning YANG ; Jinxiu WEI ; Jianfeng LI ; Mingzhu HUANG ; Lili XIE
China Pharmacy 2024;35(15):1923-1927
Hepatic fibrosis is a pathological process of chronic liver injury. Without timely intervention and treatment, liver fibrosis may eventually lead to liver cirrhosis and cancer. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is closely associated with the occurrence and development of liver fibrosis. Based on this, this paper summarized and analyzed the mechanism and effects of active ingredients and compounds of traditional Chinese medicine improving liver fibrosis based on JAK/STAT signaling pathway. It is found that the active ingredients and compounds of traditional Chinese medicine that promote blood circulation and remove blood stasis (ingredients such as ethanol extract of Euonymus alatus and paclitaxel, as well as compounds such as Ershiwuwei songshi pill and Ganfukang), clear away heat and toxic material (ingredients such as betulinic acid, total flavonoids from Persicaria perfoliata, as well as compounds such as Pianzaihuang and Kehuang capsules), and sooth the liver and promote qi circulation (ingredients such as fraxetin and cucurbitacin B, as well as compounds such as Chaihu shugan powder and Xiaochaihu decoction) can all relieve liver fibrosis by inhibiting the activity of the JAK/STAT signaling pathway, reducing inflammatory reactions, and inhibiting the proliferation of hepatic stellate cells.
9.Mechanism of Total Glucosides of Paeony in Attenuating Neurotoxicity of Aqueous Extract of Strychni Semen via GRIN2A/PLCB1/PRKCG Signaling Pathway
Siyu LI ; Kun YANG ; Changyue SONG ; Peiping CHEN ; Xinzhuo ZHANG ; Mingzhu QI ; Xiaohui SU ; Xiangying KONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):56-63
ObjectiveTo investigate the effect of total glucosides of paeony (TGP) on neurotoxicity induced by aqueous extract of Strychni Semen (SA) in mice and to explore its mechanism. MethodThirty-two male KM mice were randomly divided into normal group,SA group (19.5 mg·kg-1),TGP group (225 mg·kg-1),and SA+TGP group (SA 19.5 mg·kg-1+TGP 225 mg·kg-1). The open field test and beam walking test were used to observe the behavioral changes in mice. Pathological changes in the Nissl bodies of the cerebral cortex were assessed through Nissl staining. The levels of malondialdehyde (MDA),glutamate (Glu) in the mouse brain tissue,and serum levels of 5-hydroxytryptamine (5-HT) were detected using enzyme-linked immunosorbent assay (ELISA). Transcriptome sequencing was employed to analyze gene expression profiles in the brain tissue. Common differentially expressed genes (DEGs) underwent gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. The mRNA expression levels of key targets were determined using quantitative real-time polymerase chain reaction (Real-time PCR). ResultCompared with the normal group,the SA group exhibited significant increases in side-to-side distance and average speed in the open field test,as well as increased walking time on the balance beam. The axons of cortical neurons were absent,and the levels of Glu and MDA in the brain tissue were significantly elevated (P<0.05,P<0.01),along with a notable increase in serum 5-HT levels (P<0.05). In contrast to the SA group,the SA+TGP group significantly reduced the side-to-side distance,average speed,and balance beam walking time (P<0.05 or P<0.01). The neuronal axons were clearly visible,and levels of 5-HT,Glu,and MDA were decreased (P<0.05,P<0.01). Transcriptome analysis indicated that TGP could regulate the glutamate receptor,ionotropic,N-methyl-D-aspartate 2a (GRIN2A)/phospholipase C β1 (PLCB1)/protein kinase C,gamma (PRKCG) signaling pathway. Compared with the normal group,SA significantly decreased the expression of GRIN2A,PLCB1,and PRKCG genes in the mouse brain (P<0.01),while the mRNA levels of GRIN2A and PRKCG significantly increased after TGP administration (P<0.05,P<0.01). ConclusionSA induces significant neurotoxicity in the mouse brain,and TGP significantly alleviates SA-induced neurological damage,potentially through the GRIN2A/PLCB1/PRKCG signaling pathway.
10.Identification of Pharmacodynamic Material Basis of Ruyi Zhenbaowan by Multidimensional Correlation Model of "Pharmacodynamic-target-component-pharmacokinetic"
Mingzhu XU ; Huaiping LI ; Zhaochen MA ; Tao LI ; Yudong LIU ; Ziqing XIAO ; Chu ZHANG ; Kedian CHEN ; Weihua MA ; Feng HUANG ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):68-77
ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2, and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them, and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that, plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points, and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry(UPLC-Q-TRAP/MS), and drug concentration-time curves were plotted, then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network, a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes, such as estrogen receptor 1(ESR1), cyclic adenosine monophosphate(cAMP)-dependent protein kinase catalytic subunit alpha(PRKACA) and protein kinase B1 (Akt1), and 10 corresponding potential effect components, such as glycyrrhizic acid and betulinic acid, were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components, gallic acid, apigenin-7-O-glucuronide, glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid, with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic, this study analyzes the main effective materials of Ruyi Zhenbaowan, such as glycyrrhizic acid, gallic acid, apigenin-7-O-glucuronide and apigenin, which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.

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