1.Research progress on the improvement mechanism of traditional Chinese medicine compounds and active ingredients in schizophrenia
Xinhui YAO ; Yonghou ZHAO ; Jianbo CHAI ; Ming YU ; Xiujie QU
China Pharmacy 2024;35(9):1151-1156
Schizophrenia has various obstacles in cognition, thinking, emotion, behavior and other aspects; it belongs to the category of “madness” in traditional Chinese medicine (TCM). Once schizophrenia occurs, multiple factors are often intertwined, and a single therapy is difficult to be effective. At present, TCM compounds and active ingredients have significant effects in the clinical treatment of schizophrenia, which is an important direction for the development of new drugs for schizophrenia. This article summarizes the molecular mechanism of TCM compounds and active ingredients in the treatment of schizophrenia. It is found that Wendan decoction and Yudian decoction can inhibit the apoptosis of hippocampal cells by activating BDNF/TrKB/CREB signaling pathway; quercetin and icariin can promote neural development and regeneration by activating NMDA/ERK signaling pathway; Wendan decoction and icariin can maintain neural cell homeostasis by activating PI3K/AKT signaling pathway; Bushen zhuangyang capsule can enhance learning and memory abilities by activating CaMKⅡ signaling pathway; formulas such as Huatan huoxue tongzhi formula can enhance intercellular information transmission by inhibiting PKC signaling pathway; α-humulene and others can restore nerve cell function by inhibiting NRG1/ErbB4 signaling pathway. TCM compounds and active ingredients can improve schizophrenia by intervening in the above-mentioned signaling pathways.
2.Development and validation of a prognostic nomogram for locally advanced renal cell carcinoma patients after surgery
Fei LI ; Xiaodong WEN ; Hongqiang CHAI ; Ming WU ; Lei PANG
Journal of Modern Urology 2024;29(4):334-341
【Objective】 To construct a nomogram survival prediction model for patients with locally advanced renal cell carcinoma based on SEER database (n=7893), so as to provide reference for future prognosis study. 【Methods】 Case data were downloaded from the SEER database, and divided into the experimental group and validation group with a ratio of 7∶3 by simple randomization.The clinical information was analyzed, independent risk factors influencing prognosis were screened, and the overall survival (OS) and tumor-specific survival (CSS) were mapped.Model performance was evaluated using consistency index, area under the receiver operating characteristic curve (AUC), internal and external validation, and calibration curves. 【Results】 Patients’ age, tumor size, disease progression tpye, TNM stage, number of positive lymph nodes, marital status and pathological type were significantly correlated with OS and CSS (P<0.01).Based on the above predictors, the internal verification AUC of the 1-, 3- and 5- year OS nomogram model was 0.809, 0.721 and 0.715, respectively.The internal validation AUC of the nomogram model for 1-, 3- and 5- year CSS was 0.802, 0.745 and 0.735, respectively.The external validation AUC of the OS nomogram model was 0.792, 0.628 and 0.620 at 1, 3 and 5 years, respectively, and the external validation AUC of CSS was 0.943, 0.803 and 0.737 at 1.3 and 5 years, respectively, showing good model differentiation and accuracy. 【Conclusion】 The prediction performance of the nomogram model is good, and it can provide reference for individualized treatment.
3.Associations of alcohol, coffee, green tea and dairy products with prostate cancer: a two-sample Mendelian randomization study
Hongqiang CHAI ; Jinkai SHAO ; Ming WU ; Kejie ZHAO ; Lei PANG
Journal of Modern Urology 2024;29(3):253-260
【Objective】 A two-sample Mendelian randomization method was used to explore whether there is a causal relationship between the intake of alcohol, coffee, green tea and dairy products and the incidence of prostate cancer (PCa), in order to clarify the risk factors for the incidence of PCa and find a prevention pathway for PCa. 【Methods】 Data of alcohol, coffee, green tea, dairy products and prostate cancer were collected with genome-wide association study (GWAS).The causal relationship between their intake and the risk of PCa was analyzed with two-sample Mendelian randomization (2SMR).MR analysis was conducted with inverse-variance weighting (IVW).Sensitivity analysis was performed with weighted median, MR-Egger regression, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) tests. 【Results】 Coffee intake (OR: 0.994, 95%CI: 0.990-0.999, P=0.014) and green tea intake (OR: 0.999, 95%CI: 0.998-0.999, P=0.036) were negatively correlated with the risk of PCa.Alcohol intake (OR: 0.997, 95%CI: 0.990-1.004, P=0.392) and dairy intake (OR: 1.025, 95%CI: 0.983-1.069, P=0.256) were not associated with the risk of PCa.In weighted median, MR-Egger regression, and retention one method analyses, the results were robust without heterogeneity or pleiotropy. 【Conclusion】 There was a causal association between coffee intake and green tea intake and the onset of PCa, but no causal association between alcohol intake and dairy intake and PCa onset.
4.Prevention and Treatment of Schizophrenia by Traditional Chinese Medicine Targeting PI3K/Akt Signaling Pathway: A Review
Haiyuan WU ; Jianbo CHAI ; Ming YU ; Yonghou ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):280-289
As one of the most difficult-to-cure neuropsychiatric disorders in clinical practice, schizophrenia is mainly manifested by behavioral abnormalities and multidimensional cognitive dysfunction, and the recurrence rate and disability rate of the disease are increasing year by year, which seriously affects patients' social functioning and quality of life, and even threatens the physical and mental health of the surrounding population. At present, the treatment of schizophrenia is mainly based on antipsychotic drugs combined with psychotherapeutic techniques, which have limited long-term therapeutic effects and a high relapse rate. Traditional Chinese medicine (TCM) boasts the advantages of multi-targets, multi-pathways, multi-links, and multi-levels, and plays a crucial role in the prevention and treatment of schizophrenia and its prognosis. Phosphatidylinositol 3-kinase (PI3K) is widely present in cells and is involved in the regulation of protein synthesis and apoptosis, and the different isoforms of protein kinase B (Akt) are of great significance in cell growth, oxidative stress, neuronal development and other processes. In recent years, a large number of studies have found that the PI3K/Akt signaling pathway is closely related to schizophrenia. Through regulating the PI3K/Akt signaling pathway, TCM monomers and TCM compounds mainly affect key signaling molecules such as mammalian target of rapamycin (mTOR), glycogen synthase kinase (GSK), glucose transporter (GLUT) for glucose uptake and transport, and nuclear factor E2-associated factor 2 (Nrf2), which organize the intracellular network of centers and regulate the formation and plasticity of neuronal synapse, and they play an important role in mitigating schizophrenia by regulating the processes of cell proliferation, migration and apoptosis of neurons, and has the advantages of multi-targets, all-encompassing and low toxicity. This article analyzes and explains the mechanism of TCM intervention in the PI3K/Akt signaling pathway against schizophrenia, in order to provide a theoretical basis and reference for the prevention and treatment of schizophrenia by TCM.
5.Causal relationship between constitutional index and urinary tumors: a two-sample Mendelian randomization study
Ming WU ; Jinkai SHAO ; Hongqiang CHAI ; Lei PANG
Journal of Modern Urology 2024;29(10):898-902
[Objective] To explore the causal relationship between the body mass index (BMI) and the risk of urinary tumors using two-sample Mendelian randomization. [Methods] BMI data in IEU public database genome association and date of kidney cancer, prostate cancer, prostate cancer, bladder cancer were screened and analy through the inverse variance weighting method, MR-Egger regression analysis, weighted median analysis of two-sample mondel randomization method to evaluate the causal relationship between constitution index and urinary tumor.Finally, a sensitivity analysis was used to assess the stability and reliability of the results. [Results] Genetically-predicted BMI is positively related to the risk of kidney cancer (OR: 1.442 5, 95%CI: 1.082 1-1.923 0, P=0.012 5), negatively related to the risk of prostate cancer (OR: 0.992 6, 95%CI: 0.988 7-0.996 5, P=0.000 2), and had no causal relationship with the risk of bladder cancer (OR: 1.000 3, 95%CI: 0.999 4-1.001 1, P=0.526 9). Sensitivity analysis and pleiotropy analyses showed that the results of this study were reliable and there was no heterogeneity. [Conclusion] Genetically-predicted BMI is a risk factor for renal cancer and a protective factor for prostate cancer.It is not associated with the risk of bladder cancer.This finding can provide reference for the potential risk of common urological tumors and the development of prevention strategies.
6.Effect of Yudian decoction on brain functional connectivity in schizophrenic model rats: an functional magnetic resonance imaging study
Bing BAI ; Sihan ZHAO ; Ming YU ; Yonghou ZHAO ; Jianbo CHAI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(10):870-875
Objective:To investigate alterations in brain functional connectivity (FC) in schizophrenia (SZ) model rats treated with Yudian decoction by using functional magnetic resonance imaging (fMRI).Methods:At 17th day of gestation in healthy SPF grade SD rats, a single intraperitoneal injection of methylazoxymethanol (MAM) (25 mg/kg) was used to induce abnormalities in monoamine neurotransmitters in pregnant female rats, thereby to establish a model of neural development abnormalities in the offspring. Four weeks old male offspring were selected as SZ model rats.Thirty SZ model rats were divided into model group, experimental group, and positive control group according to the body mass matching method, with 10 rats in each group. Additionally, 10 male offspring born to healthy female rats were selected as the blank control group.At 6 weeks of age, the rats in experimental group and positive control group were administered with Yudian decoction (1.54 g/kg) and risperidone (0.24 mg/kg) by gavage, respectively. The rats in blank control group and positive control group were administered with distilled water (6.7 mL/kg) by gavage.All the above interventions were conducted once a day for 14 consecutive days.The fMRI data were acquired from all samples using a 3.0 T MRI scanner. The bilateral hippocampus, bilateral prefrontal cortex, and bilateral striatum were designated as region of interest (ROI). FC comparisons between each pair of ROIs and whole-brain FC were conducted using two-sample t-test. Results:(1) Compared to the control group, the model group demonstrated enhanced whole-brain FC at the left cerebellar granular cell level (SIGMA: x=-2, y=-107, z=48) (cluster size=43, P<0.05, FWE adjusted under cluster-level). The experimental group exhibited increased whole-brain FC at the left cerebellar molecular layer (SIGMA: x=-5, y=-152, z=36) compared to the model group (cluster size=48, P<0.05, FWE adjusted under cluster-level). (2) Using the bilateral hippocampus as ROI, the positive control group exhibited enhanced FC at the deep layer of the superior colliculus (SIGMA: x=13, y=-77, z=27) compared to the model group (cluster size=88, P<0.05, FWE adjusted under cluster-level). The blank control group displayed decreased FC at the right granular insular cortex (SIGMA: x=43, y=19, z=9) compared to the model group (cluster size=125, P<0.05, FWE adjusted under cluster-level). Utilizing the bilateral prefrontal cortex as ROI, the experimental group showed reduced FC at the left cerebellar molecular layer (SIGMA: x=-14, y=-128, z=48) compared to the blank control group (cluster size=68, P<0.05 FWE adjusted under cluster-level). Conclusion:Schizophrenia is associated with abnormal whole-brain functional connectivity, notably characterized by enhanced functional connectivity in the hippocampal region.Yudian decoction demonstrates the capability to inhibit activity in the prefrontal cortex.
7.Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress.
Yan-Rong LI ; Hui-Jie FAN ; Rui-Rui SUN ; Lu JIA ; Li-Yang YANG ; Hai-Fei ZHANG ; Xiao-Ming JIN ; Bao-Guo XIAO ; Cun-Gen MA ; Zhi CHAI
Chinese journal of integrative medicine 2023;29(1):19-27
OBJECTIVE:
To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice.
METHODS:
Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1α, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot.
RESULTS:
Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (P<0.05 or P<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, p-IRE1 α, XBP1, CHOP, Caspase-12 and Caspase-9 (P<0.05 or P<0.01).
CONCLUSIONS
WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.
8.Analysis of noise reduction measures in a noise workshop handover control room.
Rui Feng DONG ; Qing Dong WU ; Dong Liang CHAI ; Xiang Ming XUE ; Jing Ming ZHAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(5):379-382
Objective: To explore the sound insulation, sound absorption and other noise reduction transformation methods in a noise workshop handover control room. Methods: In December 2021, through the occupational health investigation and on-site testing of the handover control room of a noise workshop, the causes of excessive noise were analyzed, and the transformation design scheme to reduce noise was proposed and the effect was analyzed. Results: Before the transformation, the peak frequency band noise intensity of the noise workshop handover control room was 112.8 dB (A), and the peak frequency was 1000 Hz. After noise reduction, the theoretical calculated control value was 61.0 dB (A), and the measured noise intensity was 59.8 dB (A) . Conclusion: The noise intensity of the handover control room is reduced after noise reduction, which is in line with the contact limit requirements of the control room in GBZ 1-2010 "Hygienic Standards for the Design of Industrial Enterprises", and has reference significance for noise control engineering.
Noise/prevention & control*
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Occupational Health
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Industry
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Reference Standards
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Hygiene
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Noise, Occupational/prevention & control*
9.Effects of Yudian Decoction (愈癫汤) on the Metabolic Balance of Glu/GABA in the Brain Tissue of Schizophrenia Model Rats
Bing BAI ; Jianbo CHAI ; Ming YU ; Yonghou ZHAO
Journal of Traditional Chinese Medicine 2023;64(20):2125-2131
ObjectiveTo explore the possible mechanism of Yudian Decoction (愈癫汤) in the treatment of schizophrenia. MethodTwenty male offspring from 5 normal female 17-day-pregnant SD rats were selected as blank group. Fifteen female 17-day-pregnant SD rats were injected intraperitoneally with methyl azomethine acetate (MAM) 25 mg/kg, and the male offspring simulated the neurodevelopmental abnormality to establish a rat model of schizophrenia. Sixty successfully-modeled rats were randomly divided into 20 rats in the model group, 20 rats in the Yudian Decoction group and 20 risperidone group. After 3 days of adaptive cage feeding, the rats in the Yudian Decoction group were gavaged with 1.54 g/(kg·d) of Yudian Decoction, the risperidone group was gavaged with 0.24 mg/(kg·d) of risperidone capsule, while the blank group and the model group were gavaged with 6.7 ml/(kg·d) of distilled water, once a day, for 14 consecutive days. Sample was collected on the day after the last gavage. The expression of glutamate receptor (GluR) and γ-aminobutyric acid receptor subunit α1 (GABAARα1)-positive neurons in the hippocampus and prefrontal cortex were detected by immunofluorescence, and the positive rate was calculated; the expression of small clear proteins (PVs) in the hippocampal CA1 region and the medial prefrontal cortex was detected by immunohistochemistry; The expression of glutamic acid decarboxylase 65 (GAD65) and glutamic acid decarboxylase 67 (GAD67) proteins and mRNAs in the hippocampus and prefrontal cortex were detected by immunoblotting and reverse transcription PCR. ResultCompared with the blank group, the positive rate of GluR in hippocampal area and prefrontal cortex of rats in the model group increased, the positive rate of GABAARα1 in hippocampal area decreased, the PV optical density value in hippocampal CA1 area and medial prefrontal cortex decreased, and the expression of GAD65, GAD67 proteins and mRNA in hippocampal area and prefrontal cortex decreased (P<0.05 or P<0.01). Compared with the model group, GluR positivity rate in hippocampus and prefrontal cortex of risperidone group and Yudian Decoction decreased, GABAARα1 positivity rate in hippocampus increased, PV optical density value in hippocampus CA1 area and medial prefrontal cortex increased, and GAD65, GAD67 proteins and mRNA expression in hippocampus and prefrontal cortex increased (P<0.05 or P<0.01). Compared with the risperidone group, the positive rate of GluR in hippocampus and prefrontal cortex and GABAARα1 in hippocampus in the Yudian Decoction group was reduced, the PV optical density value of hippocampal CA1 area was increased, the protein and mRNA expression of GAD67 in hippocampus area was elevated, and the protein expression of GAD65 in prefrontal cortex was reduced (P<0.05). ConclusionYudian Decoction may improve the pathological process of schizophrenia by regulating key regulators of glutamate/γ-aminobutyric acid (Glu/GABA) metabolic balance in the hippocampus and prefrontal cortex and maintaining the balance between neuronal excitation and inhibition.

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