Geographic differences in psychological symptoms, sleep quality, and quality of life in patients with inflammatory bowel disease: A multicenter study in China.

OBJECTIVE: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). METHODS: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. RESULTS: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). CONCLUSION: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice.

Validation of the iHealth Track upper-arm blood pressure monitor KN-550BT in general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020).

OBJECTIVE: To validate the iHealth Track KN-550BT oscillometric upper-arm blood pressure monitor in general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020). METHODS: Participants were recruited and the same left-arm sequential method was used for blood pressure measurement according to the ISO 81060-2:2018+AMD1:2020. The validation results were assessed following the protocol and the Bland-Altman scatterplot was used to show the difference between the test device and reference results. RESULTS: A total of 89 qualified participants were included in the final analysis. For the validation Criterion 1, the mean ± SD of the differences between the test device and reference readings was -1.22 ±â€…5.76 mmHg and -0.08 ±â€…4.40 mmHg for systolic and diastolic blood pressure, respectively. For Criterion 2, the mean ± SD of the differences between the test device and reference readings per participant was -1.22 ±â€…5.06 mmHg and -0.08 ±â€…3.84 mmHg for systolic and diastolic blood pressure, respectively. CONCLUSION: The iHealth Track KN-550BT upper-arm blood pressure monitor passed all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020) and can be recommended for clinical use and self-measurement in general population.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Metabolomics Analysis of Electroacupuncture Pretreatment Induced Neuroprotection on Mice with Ischemic Stroke.

The brain metabolic changes caused by the interruption of blood supply are the initial factors of brain injury in ischemic stroke. Electroacupuncture (EA) pretreatment has been shown to protect against ischemic stroke, but whether its neuroprotective mechanism involves metabolic regulation remains unclear. Based on our finding that EA pretreatment significantly alleviated ischemic brain injury in mice by reducing neuronal injury and death, we performed a gas chromatography-time of flight mass spectrometry (GC-TOF/MS) to investigate the metabolic changes in the ischemic brain and whether EA pretreatment influenced these changes. First, we found that some glycolytic metabolites in the normal brain tissues were reduced by EA pretreatment, which may lay the foundation of neuroprotection for EA pretreatment against ischemic stroke. Then, 6[Formula: see text]h of cerebral ischemia-induced brain metabolic changes, especially the enhanced glycolysis, were partially reversed by EA pretreatment, which was manifested by the brain levels of 11 of 35 up-regulated metabolites and 18 of 27 down-regulated metabolites caused by cerebral ischemia significantly decreasing and increasing, respectively, due to EA pretreatment. A further pathway analysis showed that these 11 and 18 markedly changed metabolites were mainly involved in starch and sucrose metabolism, purine metabolism, aspartate metabolism, and the citric acid cycle. Additionally, we found that EA pretreatment raised the levels of neuroprotective metabolites in both normal and ischemic brain tissues. In conclusion, our study revealed that EA pretreatment may attenuate the ischemic brain injury by inhibiting glycolysis and increasing the levels of some neuroprotective metabolites.

Design and synthesis of pseudo-rutaecarpines as potent anti-inflammatory agents via regulating MAPK/NF-κB pathways to relieve inflammation-induced acute liver injury in mice.

Pseudo-natural products (PNPs) design strategy provides a great valuable entrance to effectively identify of novel bioactive scaffolds. In this report, novel pseudo-rutaecarpines were designed via the combination of several privileged structure units and 46 target compounds were synthesized. Most of them display moderate to potent inhibitory effect on LPS-induced NO production and low cytotoxicity in RAW264.7 macrophage. The results of the anti-inflammatory efficacy and action mechanism of compounds 7l and 8c indicated that they significantly reduced the release of IL-6, IL-1ß and TNF-α. Further studies revealed that they can strongly inhibit the activation of NF-κB and MAPK signal pathways. The LPS-induced acute liver injury mice model studies not only confirmed their anti-inflammatory efficacy in vivo but also could effectively relieve the liver injury in mice. The results suggest that compounds 7l and 8c might serve as lead compounds to develop therapeutic drugs for treatment of inflammation.

Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia.

Transient receptor potential vanilloid 1 (TRPV1) ion channel is a classic analgesic target, but antagonists of TRPV1 failed in clinical trials due to their side effects like hyperthermia. Here we rationally engineer a peptide s-RhTx as a positive allosteric modulator (PAM) of TRPV1. Patch-clamp recordings demonstrate s-RhTx selectively potentiated TRPV1 activation. s-RhTx also slows down capsaicin-induced desensitization of TRPV1 in the presence of calcium to cause more calcium influx in TRPV1-expressing cells. In addition, our thermodynamic mutant cycle analysis shows that E652 in TRPV1 outer pore specifically interacts with R12 and K22 in s-RhTx. Furthermore, we demonstrate in vivo that s-RhTx exhibits long-lasting analgesic effects in noxious heat hyperalgesia and CFA-induced chronic inflammatory pain by promoting the reversible degeneration of intra-epidermal nerve fiber (IENF) expressing TRPV1 channels in mice, while their body temperature remains unaffected. Our results suggest s-RhTx is an analgesic agent as a PAM of TRPV1.

PKM2 Nuclear Translocation Promotes Glial Cell Activation and Aggravates the Brain Injury of Intracerebral Hemorrhage.

BACKGROUND: The purpose of this study was to investigate the potential involvement of pyruvate kinase M2 (PKM2), an enzyme acting as a rate-limiting enzyme in the final phase of glycolysis, in the regulation of glial activation and brain damage of intracerebral hemorrhage (ICH). METHODS: Western blotting and immunofluorescence were performed to investigate PKM2 expression, terminal deoxynucleotidyl transferase deoxyurinary triphosphate (dUTP) nick end labeling staining, hematoxylin and eosin staining, and behavioral tests were employed to evaluate the brain damage of ICH mice, and RNA-seq and bioinformatic analyses were performed to detect gene expression changes in ICH mice treated with TEPP-46. RESULTS: Increased PKM2 levels in perihematomal brain tissue were found starting from 3 days following ICH and peaked at 5 and 7 days post ICH. The increased expression of PKM2 was mainly co-localized with glial fibrillary acidic protein (GFAP)+ astrocytes and ionized calcium binding adaptor molecule-1 (IBA-1)+ microglia. Furthermore, we observed a notable increase in the nuclear translocation of PKM2 in glial cells following ICH. TEPP-46 treatment significantly reduced PKM2 nuclear translocation, and effectively attenuated glial activation and brain injury, and improved functional recovery of mice with ICH. RNA-seq data indicated that 91.1% (205/225) of differentially expressed genes (DEGs) were down-regulated in the TEPP-46 treated groups compared with the vehicle-treated groups in ICH brains. Furthermore, bioinformatic analyses revealed that these down-regulated DEGs were involved in a variety of biological processes, including autophagy and metabolic processes. In addition, the majority of these downregulated DEGs had a primary high expression in neurons, with subsequent expression seen in endothelial cells, microglia, and astrocytes. CONCLUSIONS: These results indicate that increased PKM2 nuclear translocation promotes the activation of glial cells after ICH, hence aggravating ICH-induced brain damage, and aggravates the brain injury induced by ICH. This highlights a potential therapeutic target for inhibiting glial activation to attenuate brain injury after ICH.

Essential oil from the roots of Paeonia lactiflora pall. has protective effect against corticosterone-induced depression in mice via modulation of PI3K/Akt signaling pathway.

For thousands of years, the roots of Paeonia lactiflora Pall (PLP) has been considered by traditional Chinese medicine as a drug that can improve mental or emotional disorders, including depression, anxiety and affective disorders. Unfortunately, the research on the mechanism of action and active ingredients of this beneficial drug is not comprehensive. This study focused on the activity of essential oil from PLP (EOP), systematically studied the antidepressant effect of EOP for the first time, and discussed the potential mechanism of its antidepressant effect. In this study, we used a mouse model of corticosterone (CORT)-induced depression, and found that EOP had a significant antidepressant effect on the symptoms of CORT-induced depression in mice, and significantly down-regulated the levels of CRH, ACTH and cortisol in the brain tissues of mice. In addition, we found that EOP treatment alleviated CORT-induced hippocampal neuron injury in mice In vitro experiments. It was also found that EOP could inhibit CORT-induced apoptosis and improve the proliferation ability and cell viability of PC12 cells. Further, with the help of network analysis, it was revealed that PI3K-Akt might be one of the main signaling pathways of EOP against CORT-induced hippocampal neuron apoptosis. In this study, we also found that EOP up-regulated the phosphorylation of PI3K and Akt in CORT-induced mouse hippocampal neurons and PC12 cells, and promoted the nuclear transcription of Nrf2 in CORT-induced PC12 cells. In conclusion, with the integrated approach, we demonstrated that EOP exerted anti-apoptotic effects on hippocampal neurons through PI3K/Akt/Nrf2 signaling pathway.

Exploring the Oxidative Stress Regulation of Mice with Hyperglycemia by Lactiplantibacillus plantarum SCS4.

The aim of this study was to evaluate the effects of Lactiplantibacillus plantarum SCS4 (L. plantarum SCS4) on oxidative stress in streptozocin-induced hyperglycemic mice. After establishment of the hyperglycemic model, control group mice were gavaged daily with phosphate-buffered saline, while different experimental groups (AG, BG, and CG) mice were gavaged with L. plantarum SCS4 suspension, cellular inclusion suspension, and inactivated inclusion suspension for 10 weeks, respectively. Compared with the model group (MG) group, the results showed that fasting blood glucose levels in BG and CG groups decreased, and postprandial 2-h blood glucose levels in BG groups decreased, whereas glucose tolerance improved. Meanwhile, ROS and MDA levels in serum of AG mice were decreased significantly (P < 0.05). Compared with the MG group, serum levels of GPx, HO-1, and NQO1 were increased in the BG group, whereas serum levels of CAT, HO-1, and GSH were increased in the CG group. Our results indicate that L. plantarum SCS4 can alleviate oxidative stress induced by hyperglycemia, and there may be synergistic effects among the different treatments.

Alleviation of oxidative stress in pancreatic tissue of hyperglycemic mice by Lactiplantibacillus plantarum SCS4.

This study aimed to investigate the effect of Lactiplantibacillus plantarum SCS4 in alleviating oxidative stress in the pancreatic tissue of hyperglycemic mice. A total of 90 six-week-old specific pathogen-free male Kunming mice were randomly divided into six groups [normal group (NG), blank control group (MG), phosphate-buffered saline (PBS) control group (CG), SCS4 first control group (DT1), SCS4 second control group (DT2), and SCS4 third control group (DT3)]. Except the NG group, in the other five groups, streptozotocin (STZ) was intraperitoneally injected for five consecutive days to establish a hyperglycemia model; the concentration of STZ was 50 mg/kg (bw). After successful modeling, DT1, DT2, and DT3 mice were administered 0.2 ml of L. plantarum SCS4 bacterial solution (1010 colony forming unit/ml), the cellular content of L. plantarum SCS4, and the inactivated cellular content of L. plantarum SCS4, respectively. Furthermore, 0.2 ml of PBS was given to mice in the CG group for control. The levels of insulin (INS), reactive oxygen species (ROS), malondialdehyde (MDA), and antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured by enzyme-linked immunosorbent assay, and the morphology of the pancreas was observed. The results showed that after 10 weeks of gavage treatment, the level of INS in the DT3 group significantly increased to 6.36 mIU/L compared with that in the MG group (p < .05). Meanwhile, the levels of ROS and MDA of DT3 returned to normal levels of 291.07 IU/ml and 4.29 mnol/L, respectively. The activities of various antioxidant enzymes increased. The levels of SOD, CAT, and GPx in DT3 were the closest to the levels in NG. In addition, the pathological sections showed that the degree of pancreatic tissue lesions was relatively more severe in the MG group than in the NG group. The degree of pancreatic tissue lesions was relatively less severe in the DT2 group than in the MG group, and no significant lesion was seen in the DT3 group. Our results indicated that the inactivated bacterial content of L. planetarium SCS4 was more effective in improving oxidative stress in the pancreas of hyperglycemic mice. PRACTICAL APPLICATIONS: L. plantarum SCS4 was separated from fermented sausage in Sichuan. This study indicated that inactivated bacterial content of L. planetarium SCS4 was more effective in improving oxidative stress in the pancreas of hyperglycemic mice. The results suggested that lactic acid bacteria from traditional foods with ability of improving oxidative damage, which can be applied in food nutrition and related fields to make people with good dietary habits and prevent the occurrence of chronic diseases such as type II diabetes effectively.

Health benefits of spices in individuals with chemotherapeutic drug-induced cardiotoxicity.

Cardio-oncology is an emerging field that mainly focuses on a series of cardiovascular diseases caused by chemotherapy and radiotherapy. In the history and culture of human nutrition, spices have been emphasized for their wide range of economic and medical applications in addition to being used as a food-flavoring agent and food preservative. Currently, an increasing number of studies have focused on the health benefits of spices in preventing cardiovascular diseases, particularly their antioxidant effects against cardiovascular damage. This review summarizes the cardioprotective effects of black pepper, cardamom, clove, garlic, ginger, onion, and other spices against chemotherapeutic drug-induced cardiotoxicity and the potential mechanisms. Here, we recommend dietary adjustments with spices for patients with cancer to prevent or mitigate the cardiotoxicity induced by chemotherapeutic agents.

Association between body mass index, waist circumference, and age at natural menopause: a population-based cohort study in Chinese women.

The purpose of the study was to investigate whether premenopausal body mass index (BMI) and waist circumference (WC) influence age at menopause. A total of 2116 women aged 35-64 years from two communities of the CMCS Beijing cohort were recruited in 1992 and followed up to 2018. Of 1439 premenopausal women at baseline, 6 women data were missing. Finally, 1433 women were included for analysis. Overweight was defined as BMI 24-27.99 kg/m2. Central obesity was defined as WC ≥80 cm. Age at menopause was categorized as <45 years, 45-49 years, 50-51 years (reference), and >51 years. Multinomial logistic regression models were used to estimate relative odds ratios (RORs) and 95% confidence intervals (CIs). Compared to women with normal weight and normal WC, overweight women with normal WC had higher risk of menopause at >51 years (ROR 1.64, 95% CI 1.10-2.45; P = .01); and overweight women with central obesity had higher risk of menopause at not only >51 years (ROR 1.82, 95% CI 1.13-2.93; P = .01) but also <45 years (ROR 3.13, 95% CI 1.20-8.43; P = .02) and 45-49 years (ROR 2.76, 95% CI 1.71-4.46; P < .001). When overweight women combine with central obesity, the risk of early menopause will increase in some of them.

Antiepileptic Effects of Cicadae Periostracum on Mice and Its Antiapoptotic Effects in H2O2-Stimulated PC12 Cells via Regulation of PI3K/Akt/Nrf2 Signaling Pathways.

Cicadae Periostracum (CPM), a commonly used animal traditional Chinese medicine (TCM), possesses antifebrile, spasmolytic, antiasthmatic, and antiphlogistic effects. In our present paper, we aimed to systemically investigate the antiepileptic effects of CPM in epileptic mice and explore the related molecular mechanism. Pentylenetetrazole- (PTZ) and strychnine-induced convulsion mice were established, and the results showed CPM could prolong the latency of convulsion and death and improve the neuronal damage in the hippocampus of PTZ-induced mice. Furthermore, the H2O2-treated PC12 cells were prepared to explore the possible mechanisms for the antiepileptic effects of CPM. CCK-8 results showed that CPM significantly improved the cell viability of H2O2-treated PC12 cells. Results of the acridine orange- (AO-) ethidium bromide (EB) staining, cell mitochondrial membrane potential (MOMP) analysis, and flow cytometry analysis showed that CPM significantly suppressed the H2O2-induced apoptosis in PC12 cells. In addition, CPM also downregulated the proapoptosis proteins, including Bax, cleaved- (C-) caspase-3, and C-caspase-9, and upregulated Bcl-2. Furthermore, CPM reduced the reactive oxygen species (ROS) levels via increasing antioxidative enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Importantly, CPM could increase the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in H2O2-induced PC12 cells and can promote the nuclear transfer of the nuclear factor E2-related factor 2 (Nrf2) and increase the expression of heme oxygenase-1 (HO-1) in the cytoplasm. In conclusion, our present study suggested CPM possessed antiepileptic effects through antiapoptosis of neuron cells via regulation of the PI3K/Akt/Nrf2 signaling pathway.

Exploring the antioxidant effect of Lactobacillus plantarum SCS2 on mice with type 2 diabetes.

This study aimed to evaluate the antioxidant effect of Lactobacillus plantarum SCS2 (L. plantarum SCS2). After 1 week of acclimation, 120 male KM mice were divided into normal group (NG), model group (MG), solvent control group (KG), and different test groups (TG1, TG2, TG3) (n = 20/group) randomly. In the second week, except NG mice, other mice were given 0.2 ml 50 mg/kg (body weight) streptozocin (STZ) through intraperitoneal injection for 5 days. After successful modeling, NG and MG mice were fed normally, KG mice was given 0.5 ml 0.1 mol/L phosphate buffer saline (PBS) per day, TG1, TG2, and TG3 mice were given 0.5 ml suspension, intracellular content and heat-killed intracellular content of L. plantarum SCS2 per day for 9 weeks. Body weight and blood glucose were observed and recorded during intragastric administration. Glucose tolerance levels were measured at the twelfth week, then mice were sacrificed and the serum was collected to measure insulin (INS), glycosylated hemoglobin (HbA1c), malondialdehyde (MDA), reactive oxygen species (ROS) and antioxidant enzymes. The results showed that the reduction of weight loss in TG1 and TG2 mice was observed, which was consistent with the blood glucose. At the same time, the INS level of TG1, TG2, and TG3 mice were increased and the HbA1c levels were decreased. Otherwise, the MDA and ROS content in the serum of TG1, TG2, and TG3 mice were decreased and the level of antioxidant enzymes was increased. Interestingly, the activity and content of antioxidant enzymes in TG2 group was the highest in the three test groups. PRACTICAL APPLICATIONS: The results of this study showed that L. plantarum SCS2 could effectively reduce blood glucose, relieve weight loss, improve INS deficiency, and also improve oxidative stress by increasing the activity of antioxidant enzymes. The findings suggest that L. plantarum SCS2 could improve diabetes-related symptoms by alleviating oxidative stress. In the future, people could promote the application of lactic acid bacteria (LAB) which is found in traditional foods with the ability of improving oxidative damage in food nutrition and related fields, so as to guide residents to form good dietary habits, and effectively prevent type 2 diabetes. Meanwhile, it also can enhance the edible value of traditional foods.

Association between cumulative blood pressure and long-term risk of cardiovascular disease: findings from the 26-year Chinese Multi-provincial Cohort Study-Beijing Project.

BACKGROUND: Cumulative blood pressure (BP), a measure incorporating the level and duration of BP exposure, is associated with the risk of cardiovascular disease (CVD). However, the level at which cumulative BP could significantly increase the risk remains unclear. This study aimed to investigate the association of 15-year cumulative BP levels with the long-term risk of CVD, and to examine whether the association is independent of BP levels at one examination. METHODS: Data from a 26-year follow-up of the Chinese Multi-provincial Cohort Study-Beijing Project were analyzed. Cumulative BP levels between 1992 and 2007 were calculated among 2429 participants free of CVD in 2007. Cardiovascular events (including coronary heart disease and stroke) occurring from 2007 to 2018 were registered. Adjusted hazard ratios (HRs) for CVD incidence associated with quartiles of cumulative systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated. RESULTS: Of the 2429 participants, 42.9% (1042) were men, and the mean age in 2007 was 62.1 ±â€Š7.9 years. Totally, 207 CVD events occurred during the follow-up from 2007 to 2018. Participants with higher levels of cumulative SBP or DBP exhibited a higher incidence rate of CVD (P < 0.001). Compared with the lowest quartile of cumulative SBP, the HR for CVD was 1.03 (95% confidence interval [CI]: 0.59-1.81), 1.69 (95% CI: 0.99-2.87), and 2.20 (95% CI: 1.21-3.98) for the second to the fourth quartile of cumulative SBP, and 1.46 (95% CI: 0.86-2.48), 1.99 (95% CI: 1.18-3.35), and 2.08 (95% CI: 1.17-3.71) for the second to the fourth quartile of cumulative DBP, respectively. In further cross-combined group analyses with BP measurements in 2007, 15-year cumulative BP levels higher than the median, that is, 1970.8/1239.9 mmHg·year for cumulative SBP/DBP, which were equivalent to maintaining SBP/DBP levels of 131/83 mmHg or above on average in 15 years, were associated with higher risk of CVD in subsequent years independent of BP measurements at one-time point. CONCLUSION: Cumulative exposure to moderate elevation of BP is independently associated with increased future cardiovascular risk.

Inducing Apoptosis and Suppressing Inflammatory Reactions in Synovial Fibroblasts are Two Important Ways for Guizhi-Shaoyao-Zhimu Decoction Against Rheumatoid Arthritis.

BACKGROUND AND OBJECTIVES: Guizhi-Shaoyao-Zhimu decoction (GSZD) is often applied to control rheumatoid arthritis (RA), gout, osteoarthritis, etc. In this study, bioinformatic analysis and experimental verification were used to uncover the integral mechanism profile of GSZD against RA. MATERIALS AND METHODS: The chemical compositions of GSZD were identified by UPLC-QTOF-MS/MS. MH7A cell model was established to screen active compounds in GSZD, and potential targets of these compounds were predicted through online database retrieval. The differential expression genes (DEGs) in synovial tissue of RA patients and normal controls were retrieved from the GEO database. DEGs and the predicated compounds targets were overlapped, and the overlapped genes were subsequently enriched by GO and KEGG analysis. The pathways with significant enrichments were further experimentally verified. RESULTS: A total of 19 constituents were identified from GSZD, and 11 compounds showed obviously antiproliferative effects on MH7A cells with IC50 < 100 µg/mL. Bioinformatic analysis indicated that IL-1ß, IL-6, MAPK8, JAK2, CXCL8, and CASP3 were the main targets of GSZD, and the integral pharmacological mechanisms profile of GSZD might be related to anti-inflammation and proapoptosis. GSZD can promote the loss of mitochondrial membrane potential (MOMP) and induce apoptosis in MH7A cells. Furthermore, in vitro experiments showed GSZD can not only downregulate mRNA expressions of IL-1ß (p<0.05), IL-6 (p<0.05), MMPs (p<0.05) and CCL5 (p<0.05) but also inhibit the nuclear transcription of NF-κB. GSZD also reduced the expressions of Bcl-2 (p<0.05), JAK2 (p<0.05), STAT-3 (p<0.05), whereas increase Bax (p<0.05), Caspase-3 (p<0.05) and caspase-9 (p<0.05). CONCLUSION: Collectively, inducing synovial fibroblast apoptosis and inhibiting inflammatory response are two important ways for GSZD to RA, and our study proved bioinformatic analysis combined with experimental verification is a feasible method to explore the drug targets and mechanism of actions of TCMs.

Combined effect of menopause and cardiovascular risk factors on death and cardiovascular disease: a cohort study.

BACKGROUND: Observational studies suggest that early menopause is associated with increased risk of death and cardiovascular disease (CVD); however, the results of these studies have been inconsistently. We aimed to assess the association of menopause with death and CVD and whether this association was modified by cardiovascular risk factors. METHODS: The study population was women age 35-64 years living in two communities of Beijing who were enrolled in the Chinese Multi-provincial Cohort Study in 1992. Participants were followed until first cardiovascular event, death, or the end of follow-up (2018). Self-reported age at menopause was recorded. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of death and CVD after adjusting for baseline covariates of age, family history of CVD, and white blood cell count, as well as time-varying covariates of menopause, use of oral estrogen, and conventional risk factors. Additionally, we assessed the combined effect of age at menopause and risk factors on the primary endpoint. RESULTS: Of 2104 eligible women, 124 died and 196 had a first CVD event (33 fatal CVD and 163 non-fatal CVD). Compared with women who experienced menopause at age 50-51 years, the risk of death was higher in women with menopause at age 45-49 years (HR 1.99, 95% CI 1.24-3.21; P = 0.005), and the risk of ischemic stroke was higher in women with menopause at age < 45 years (HR 2.16, 95% CI 1.04-4.51; P = 0.04) and at age 45-49 years (HR 2.05, 95% CI 1.15-3.63; P = 0.01). Women who had menopause before age 50 years and at least one elevated risk factor at baseline had a higher risk of death (HR 11.10, 95% CI 1.51-81.41; P = 0.02), CVD (HR 3.98, 95% CI 1.58-10.01; P = 0.003), ischemic CVD (HR 4.53, 95% CI 1.63-12.62; P = 0.004), coronary heart disease (HR 8.63, 95% CI 1.15-64.50; P = 0.04), and stroke (HR 2.92, 95% CI 1.03-8.29; P = 0.04) than those with menopause at age 50-51 years and optimal levels of all risk factors. CONCLUSIONS: Earlier menopause may predict death and ischemic stroke. Furthermore, there is a combined effect of earlier menopause and elevated risk factors on death and CVD.

Association of menopause with risk of carotid artery atherosclerosis.

OBJECTIVES: Observational studies suggest that the risk of cardiovascular disease increases during menopause; however, the menopause-related risk of subclinical atherosclerosis is unclear. The aim of the current study is to evaluate menopause and the risk of subclinical carotid atherosclerosis through a retrospective analysis of data from a population-based prospective cohort study. STUDY DESIGN: The study sample comprised 879 women in the Beijing community enrolled in the Chinese Multi-provincial Cohort Study at baseline study in 1992 and followed up to at least one carotid ultrasound examination at three on-site follow-up surveys. Age at menopause was categorized as <40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early menopause), 50-51 years (reference), and >51 years (relatively late menopause). Menopause staging at baseline was categorized as: reproductive, menopausal transition/perimenopause, early postmenopause, and late postmenopause. Menopause as a time-varying covariate was calculated using waiting time to menopause and menopause status at the last follow-up (2012). MAIN OUTCOME MEASURES: The main outcome measures included carotid plaque and intima-media thickening. Gray's test was performed to assess the equality of cumulative incidence functions between age groups at menopause and between menopause stages. Multivariate Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with menopause. RESULTS: Of the 879 women included (mean [SD] age at baseline, 48.6 [8.1] years), 573 (65.2%) developed carotid plaques and 430 (48.9%) developed intima-media thickening during follow-up. Menopause was significantly associated with risk of developing carotid plaques (HR 1.93, 95% CI 1.05-3.54; P = 0.03) after adjustment for age at baseline, age at menopause, use of oral estrogen due to menopause, and traditional cardiovascular risk factors at baseline. No significant association was found between age at menopause and risk of carotid atherosclerosis. CONCLUSION: Menopausal women, irrespective of age at menopause, had an increased risk of carotid plaque.

Hydroxy-α-sanshool Possesses Protective Potentials on H2O2-Stimulated PC12 Cells by Suppression of Oxidative Stress-Induced Apoptosis through Regulation of PI3K/Akt Signal Pathway.

Zanthoxylum bungeanum pericarp is a commonly used herbal medicine in China with effects of anti-inflammatory and analgesic, improving learning and memory ability, while hydroxy-α-sanshool (HAS) is the most important active ingredient of Z. bungeanum pericarps. The purpose of this study was to investigate the neuroprotective effect of HAS and its related possible mechanisms using a H2O2-stimulated PC12 cell model. CCK-8 assay results showed that HAS had a significant protective effect on H2O2-stimulated PC12 cells without obvious cytotoxicity on normal PC12 cells. Flow cytometry and fluorescence microscope (DAPI staining and DCFH-DA staining) indicated that HAS could reduce the H2O2-induced apoptosis in PC12 cells via reduction of intracellular ROS and increase of mitochondrial membrane potential (MMP). Subsequently, results of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) determination suggested that HAS could increase the enzyme activities of SOD, CAT, and GSH-Px whereas it could decrease the MDA contents in H2O2-stimulated PC12 cells. Furthermore, the western blotting assays showed that HAS could upregulate the expressions of p-PI3k, Akt, p-Akt, and Bcl-2, while it could downregulate the expressions of cleaved caspase-3 and Bax in H2O2-stimulated PC12 cells. Collectively, it could be concluded according to our results that HAS possesses protective potentials on H2O2-stimulated PC12 cells through suppression of oxidative stress-induced apoptosis via regulation of PI3K/Akt signal pathway.

Traditional Chinese Medicine: Role in Reducing ß-Amyloid, Apoptosis, Autophagy, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease characterized by memory loss and cognitive impairment. The major characteristics of AD are amyloid ß plaques, apoptosis, autophagy dysfunction, neuroinflammation, oxidative stress, and mitochondrial dysfunction. These are mostly used as the significant indicators for selecting the effects of potential drugs. It is imperative to explain AD pathogenesis and realize productive treatments. Although the currently used chemical drugs for clinical applications of AD are effective in managing the symptoms, they are inadequate to achieve anticipated preventive or therapeutic outcomes. There are new strategies for treating AD. Traditional Chinese Medicine (TCM) has accumulated thousands of years of experience in treating dementia. Nowadays, numerous modern pharmacological studies have verified the efficacy of many bioactive ingredients isolated from TCM for AD treatment. In this review, representative TCM for the treatment of AD are discussed, and among these herbal medicines, the Lamiaceae family accounts for the highest proportion. It is concluded that monomers and extracts from TCM have potential therapeutic effect for AD treatment.