ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.

ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Objective To analyze the prevalence and related risk factors of mild cognitive impairment (MCI) in the elderly in Zhoukanghang region of Pudong New Area,Shanghai. Methods Clinical data of 1537 elderly people (aged≥60 years old) in Zhoukanghang region of Pudong New Area,Shanghai from Aug. 2019 to Sep. 2022 were collected. Demographic data,cardiovascular risk factors (blood pressure,blood glucose,blood lipids,etc.),family history of dementia,cerebrovascular history,and hippocampal magnetic resonance imaging data were collected,and the MCI was tested by the simple mental state scale (MMSE) and Montreal cognitive assessment (MoCA). According to the clinical diagnostic criteria of MCI,the subjects were divided into MCI group and non-MCI group. The clinical data were compared between the 2 groups,and the independent risk factors of MCI were analyzed by multivariate logistic regression analysis. Results Among the 1537 subjects,226 cases (14.70％) were MCI patients and 1311 cases (85.30％) were non-MCI individuals. Among the 226 patients with MCI,138 had single domain amnestic MCI,33 had multiple domain amnestic MCI,11 had single domain non-amnestic MCI,and 7 had multiple domain non-amnestic MCI. The proportions of male,diabetes mellitus,hyperlipidemia,family history of dementia and cerebrovascular disease in the MCI group were significantly higher than those in the non-MCI group (all P<0.05),and the hippocampal atrophy was significantly higher than that in the non-MCI group (P<0.01). Multivariate logistic regression analysis showed that family history of dementia,cerebrovascular history and hippocampal atrophy were independent risk factors for MCI in the elderly (all P<0.05). Totally 214 patients with MCI were followed up to Feb. 2023,of which 20 cases (9.35％) were diagnosed as Alzheimer's disease and 4 cases (1.87％) as Lewy bodies dementia. Conclusion The prevalence of MCI in the elderly in Zhoukanghang region of Pudong New Area,Shanghai is 14.70％. Family history of dementia,cerebrovascular disease and hippocampal atrophy are independent factors for MCI in the elderly.

【Objective】 Coronary no-reflow during percutaneous conranary intervention (PCI) often results in the failure of ischemic myocardial reperfusion and major adverse cardiovascular events (MACE). The present study sought to evaluate whether the GRACE risk score can predict coronary no-reflow in STEMI patients undergoing PCI. 【Methods】 We consecutively recruited 1 118 patients with STEMI who were admitted to Gansu Provincial People’s Hospital and The First Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2011. Main demographic data, cardiovascular risk factors, blood lipid and other biochemical indicators were recorded. Coronary angiography was performed by a radial artery approach using the standard Judkins technique. Coronary no-reflow was evaluated by at least two independent experienced cardiologists. The GRACE risk score was calculated with a computer program. All the cases were followed up by medical records, face-to-face interviews or telephone calls. Finally, we analyzed the predictive value of the GRACE risk score for coronary non-reflow and MACE in STEMI patients undergoing PCI. 【Results】 During a median period of 36 months, 58 of the 1 118 patients (5.2%) were lost to follow-up. Of the remaining 1 060 patients, 118 (11.1%) had no-reflow and 147 (13.9%) had MACE. The GRACE score was higher in patients with no-reflow than those without no-reflow. Multivariate logistic regression established that the GRACE score was an independent predictor for coronary no-reflow (OR=1.034; P=0.002). And multivariate Cox analysis showed the GRACE score was an independent predictor of MACE. The area under the ROC curve for coronary no-reflow and MACE was 0.719 and 0.697, respectively. Kaplan-Meier analysis showed that the probability of rehospitalization for heart failure, reinfarction, all-cause death and cumulative cardiovascular events increased with the increase of the GRACE risk score. 【Conclusion】 The GRACE risk score is a readily available predictive scoring system for coronary no-reflow and MACE in STEMI patients.

Objective:To investigate the relationship between prolonged PR interval and carotid atherosclerosis(CAS)in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods:A total of 537 middle-aged and elderly inpatients with T2DM in the Southern Branch of the Sixth People′s Hospital of Shanghai Jiaotong University from January 2019 to January 2021 were selected as the research objects. Color Doppler ultrasound was used to detect bilateral carotid artery intima-media thickness(CIMT). The subjects were divided into carotid atherosclerosis group(CAS group, n=352)and non-carotid atherosclerosis group(NCAS group, n=185). The difference in the PR interval of ECG between the two groups was compared. Pearson or Spearman rank correlation analysis was used for evaluating the correlation of PR interval and CAS lesions with various clinical index. The relationship between PR interval and CAS lesions was adopted by multivariate logistic regression analysis. Results:The average PR interval of middle-aged and elderly patients with T2DM was(164.57±23.02)ms. The average PR interval in CAS group was significantly higher than that in NCAS group [(169.76±24.28) vs (154.70±16.42)ms, P<0.01]. The results of multifactorial logistic regression analysis showed that age, low density lipoprotein-cholesterol, serum osteocalcin, and PR interval were independent factors influencing the development of CAS lesions in middle-aged and elderly patients with T2DM( OR=1.079, 1.936, 0.879, 1.039, respectively, P<0.05 or P<0.01)where each 1 ms increase in PR interval was associated with a 3.9% increase in the risk of CAS in middle-aged and elderly patients with T2DM( OR=1.039, 95% CI 1.006-1.073, P=0.020). Multivariate logistic regression analysis showed that middle-aged and elderly type 2 diabetic patients with PR interval≥158 ms were 4.072 times more likely to have CAS lesions than those with PR interval<158 ms( OR=4.072, 95% CI 1.417-11.702, P<0.01). Conclusion:The PR interval of electrocardiogram is correlated with CAS lesions in middle-aged and elderly patients with T2DM. Middle-aged and elderly type 2 diabetic patients with significantly prolonged PR interval should be reminded to screen for CAS lesions early.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

The 29th International Symposium on Amyotrophic Lateral Sclerosis (ALS)-Motor Neuron Disease was held in Glasgow from December 7 to 9, 2018. The symposium was divided into 23 topics, with 109 special reports and paper′s exchange and 515 posters exchange. This article briefly introduces some topics of the symposium, involving basic researches, clinical researches and clinical trials. Among these, basic researches include genetics and genomics, axonal degeneration, disease models, and preclinical therapeutic strategies; Clinical researches include epidemiology, clinical progression, cognitive and psychological change, neuropathology, neurophysiology, neuroimaging and biomarkers.

The 29th International Symposium on Amyotrophic Lateral Sclerosis (ALS)?Motor Neuron Disease was held in Glasgow from December 7 to 9, 2018. The symposium was divided into 23 topics, with 109 special reports and paper′s exchange and 515 posters exchange. This article briefly introduces some topics of the symposium, involving basic researches, clinical researches and clinical trials. Among these, basic researches include genetics and genomics, axonal degeneration, disease models, and preclinical therapeutic strategies; Clinical researches include epidemiology, clinical progression, cognitive and psychological change, neuropathology, neurophysiology, neuroimaging and biomarkers.