Non-linear association between long-term air pollution exposure and risk of metabolic dysfunction-associated steatotic liver disease

BACKGROUND@#Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) has become a global epidemic, and air pollution has been identified as a potential risk factor. This study aims to investigate the non-linear relationship between ambient air pollution and MASLD prevalence.@*METHOD@#In this cross-sectional study, participants undergoing health checkups were assessed for three-year average air pollution exposure. MASLD diagnosis required hepatic steatosis with at least 1 out of 5 cardiometabolic criteria. A stepwise approach combining data visualization and regression modeling was used to determine the most appropriate link function between each of the six air pollutants and MASLD. A covariate-adjusted six-pollutant model was constructed accordingly.@*RESULTS@#A total of 131,592 participants were included, with 40.6% met the criteria of MASLD. "Threshold link function," "interaction link function," and "restricted cubic spline (RCS) link functions" best-fitted associations between MASLD and PM2.5, PM10/CO, and O3 /SO2/NO2, respectively. In the six-pollutant model, significant positive associations were observed when pollutant concentrations were over: 34.64 µg/m3 for PM2.5, 57.93 µg/m3 for PM10, 56 µg/m3 for O3, below 643.6 µg/m3 for CO, and within 33 and 48 µg/m3 for NO2. The six-pollutant model using these best-fitted link functions demonstrated superior model fitting compared to exposure-categorized model or linear link function model assuming proportionality of odds.@*CONCLUSION@#Non-linear associations were found between air pollutants and MASLD prevalence. PM2.5, PM10, O3, CO, and NO2 exhibited positive associations with MASLD in specific concentration ranges, highlighting the need to consider non-linear relationships in assessing the impact of air pollution on MASLD.

Stellate Ganglion Block as an Adjunctive Intervention for Chronic Subjective Tinnitus： Efficacy and Predictive Indicators / 中山大学学报(医学科学版)

ObjectiveTo explore the efficacy and predictive indicators of stellate ganglion block （SGB） as an adjunctive intervention for chronic subjective tinnitus and accumulate experience for the application of SGB in the clinical treatment of tinnitus. MethodsA retrospective review was conducted on the data of chronic subjective tinnitus patients who received SGB intervention， with unsatisfactory outcomes otherwise. Pure tone audiometry （PTA）， tinnitus loudness evaluation and Pittsburgh sleep quality index （PSQI） were used. The tinnitus handicap inventory （THI） scores were compared before and after SGB intervention. Correlation analysis and linear regression equations were employed to identify the potential indicators predicting the effectiveness of SGB intervention. Statistical analysis was performed by SPSS 24.0 software. ResultsBy April 2023， a total of 107 patients with chronic subjective tinnitus had undergone SGB intervention， including 67 male and 40 female， with a mean age of （45.32±11.40） years old and an average tinnitus history of （20.32±24.64） months ［16 （12~20）］. Only 7 patients （6.54%） quitted the intervention for personal reasons， which demonstrated good compliance with the intervention. No patients experienced adverse reactions such as infection at the injection site， hematoma， nerve injury， local anesthetic intoxication and so on， which revealed good safety. After SGB intervention， THI scores decreased to below 36 points in 77 patients and decrease by 10 points or more in 12 of the remaining patients， with a total effective rate of 89%. A paired sample t-test showed a significant difference in THI scores before and after SGB intervention （t=15.575， P<0.001）， indicating good improvement. Pearson correlation analysis suggested that pre-intervention THI scores and subjective tinnitus loudness were significantly positively correlated with the improvement level of THI scores （P<0.05）. Further stepwise linear regression analysis found that "pre-intervention THI scores" had statistical significance （P<0.001）， with a regression coefficient of 0.308， predicting a 17.4% improvement level in THI scores. ConclusionsDue to its good and safe short-term effects， SGB intervention can be used as a supplementary option for chronic subjective tinnitus when other interventions are not ideal， especially for patients with higher THI scores. However， further research is needed to clarify the long-term efficacy and underlying mechanisms， in order to establish a more solid theoretical basis for SGB intervention in the treatment of subjective tinnitus.

Effects of Molybdenum Doping on the Enhanced Electrocatalytic Nitrogen Reduction Reaction Performance of CeO2 Nanorods: Theoretical and Experimental Investigations.

As a green and sustainable strategy, the electrocatalytic N2 reduction reaction (NRR) has been considered the best potential approach to replace the traditional Haber-Bosch process under ambient conditions. The key is to exploit efficient and low-cost electrocatalysts according to the current situation. Herein, a series of Molybdenum (Mo) doped CeO2 nanorods (NR) catalysts were successfully fabricated via a hydrothermal reaction coupled with high temperature calcination. The nanorod structures were not altered after Mo atom doping. The obtained 5 %-Mo-CeO2 nanorods act as a superior electrocatalyst in neutral electrolytes of 0.1 M Na2 SO4 . Such electrocatalyst significantly enhances NRR performance with an NH3 yield of 10.9 µg h-1 mg-1 cat at -0.45 V vs reversible hydrogen electrode (RHE) and a Faradaic efficiency (FE) of 26.5 % at -0.25 V vs RHE. That outcome is 4 times higher than that of CeO2 nanorods (2.6 µg h-1 mg-1 cat ; 4.9 %). Meanwhile, density functional theory (DFT) calculation shows the characteristics after Mo doping: the band gap value lowers, the density of states increases, electrons are more easily excited, and N2 molecules are more easily adsorbed, thereby enhancing the activity of the electrocatalytic NRR.

Robot-assisted minimally invasive coronary artery bypass in treating multi-vessel coronary artery disease: A retrospective study in a single center / 中国胸心血管外科临床杂志

@#Objective    To evaluate the early and mid-term results of robot-assisted coronary artery bypass grafting (RACAB) in the treatment of multi-vessel coronary artery disease (MV-CAD). Methods     Patients with MV-CAD who underwent RACAB from April 2018 to December 2021 in our hospital were included. Patients who underwent hybrid coronary revascularization (HCR) which combined RACAB with percutaneous coronary intervention were allocated to a HCR-RACAB group, and patients who underwent multi-vessel RACAB were allocated to a MV-RACAB group. Perioperative and follow-up data were collected and compared between the two groups. Results     A total of 102 patients were included, including 81 males and 21 females with a mean age of 61.7±10.8 years. Two (2.0%) patients were transferred to conventional CABG due to sudden ventricular fibrillation and pleura adhesion. In the remaining 100 patients who underwent RACAB, 100 left internal mammary arteries (LIMA) and 46 right internal mammary arteries (RIMA) were harvested with a 100.0% success rate. Besides, all patients undergoing RACAB achieved LIMA/RIMA-left anterior descending branch reconstruction, with an average number of 2.5±0.6 target vessels revascularized by stent or graft. One patient had perioperative myocardial infarction with an outcome of death. The incidence of major perioperative adverse events was 1.0%. There was no perioperative stroke or re-sternotomy for hemostasis. The mean follow-up time was 28.2 months, with a follow-up rate of 99.0% and an overall major adverse cardiac and cerebrovascular event (MACCE) rate of 7.0%, including 3 all-cause deaths (3.0%), 2 strokes (2.0%) and 3 re-revascularizations (3.0%). The HCR-RACAB group had fewer red blood cell transfusion (P=0.030) and intraoperative blood loss (P=0.037) compared with the MV-RACAB group, and there was no statistical difference in the incidence of major perioperative adverse events or MACCE between the two groups during the follow-up period (P>0.05). Conclusion    RACAB can be safely applied in the treatment of MV-CAD with good early and mid-term outcomes. High-quality harvesting of LIMA/RIMA and aortic no-touch technique are crucial to achieve these results.

Heterogeneity of the tumor immune microenvironment and clinical interventions / 医学前沿

The tumor immune microenvironment (TIME) is broadly composed of various immune cells, and its heterogeneity is characterized by both immune cells and stromal cells. During the course of tumor formation and progression and anti-tumor treatment, the composition of the TIME becomes heterogeneous. Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales. Owing to the existence of TIME, clinical outcomes can differ when a similar treatment strategy is provided to patients. Therefore, a comprehensive assessment of TIME heterogeneity is essential for developing precise and effective therapies. Facilitated by advanced technologies, it is possible to understand the complexity and diversity of the TIME and its influence on therapy responses. In this review, we discuss the potential reasons for TIME heterogeneity and the current approaches used to explore it. We also summarize clinical intervention strategies based on associated mechanisms or targets to control immunological heterogeneity.

Postoperative corneal topography generation based on attention mechanism and Pix2Pix network / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the use of attention mechanism and Pix2Pix generative adversarial network to predict the postoperative corneal topography of age-related cataract patients undergone femtosecond laser arcuate keratotomy.METHODS:In this retrospective case series study, the 210 preoperative and postoperative corneal topographies from 87 age-related cataract patients(105 eyes)undergoing femtosecond laser arcuate keratotomy at Shanxi Eye Hospital between March 2018 and March 2020 were selected and divided into a training set(180)and a test set(30)for model training and testing. The peak signal-to-noise ratio(PSNR), structural similarity(SSIM)and Alpins astigmatism vector analysis were used to compare the accuracy of postoperative corneal topography prediction under different attention mechanisms.RESULTS:The model based on attention mechanism and Pix2Pix network can predict postoperative corneal topography, among which the model based on Self-Attention mechanism has the best prediction effect, with PSNR and SSIM reaching 16.048 and 0.7661, respectively. There were no statistically significant differences in the difference vector, difference vector axis position, surgically induced astigmatism, and correction index between real and generated corneal topography on the 3mm and 5mm rings(all P&#x003E;0.05).CONCLUSION:Based on the Self-Attention mechanism and Pix2Pix network, the postoperative corneal topography can be well predicted, which can provide reference for the surgical planning and postoperative effects of ophthalmic clinicians.

Sample size determination for comparing accuracies between two diagnostic tests under a paired design.

With the progressive technology, many medical researches are aimed to develop diagnostic tests that can detect diseases faster and accurately. The assessment of the accuracy of the diagnostic test for classifying two groups is through the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). When a paired design is considered, the sample size determination requires the information about two AUC estimates and the corresponding variance and covariance of two AUC estimators. This paper derives the nonparametric estimators of the variance and covariance of two AUC estimators. The result is used to derive the sample size formula when the paired sample is planned. Since most of the results do not have a closed form, numerical results are provided under various scenarios.

Bi2S3 quantum dots in situ grown on MoS2 nanoflowers: An efficient electron-rich interface for photoelectrochemical N2 reduction.

Photoelectrocatalysis is considered a green, environmentally friendly, sustainable technology for NH3 synthesis. However, the low efficiency of ammonia synthesis is currently the primary problem in photoelectrochemical nitrogen reduction reactions (PEC NRR). Herein, a nanocomposite BQD/MS developed through the in-situ growth of Bi2S3 quantum dots (BQD) on MoS2 (MS) nanoflowers was demonstrated as an efficient PEC NRR catalyst. Experimental results showed that the strong interaction between BQD and MS modulated the interfacial charge distribution and increased the electron density on the MS side. Meanwhile, the excellent structure of BQD/MS promoted the effective migration of photogenerated electrons from excited BQD to the MS surface. The electron-rich MS reaction interface was conducive to cleaving the stable NN bond and improving the N2 reduction performance. As a result, the prepared BQD/15MS photocathode obtained an excellent Faradaic efficiency of 33.2% and an NH3 yield of 18.5 µg h-1 mg-1, which was about three times that of bare MS.

Risk of Stroke in Patients with Breast Cancer and Sleep Disorders.

Breast cancer and stroke were leading cause of cancer-related mortality in the world. Stroke is the second leading cause of death. Previous studies showed that patients with breast cancer had a relatively higher risk of sleep disorders. Sleep disorders increased the risk of stroke. The aim of our study was to examine the risk of stroke after a breast cancer with sleep disorder among women in Taiwan. The Taiwan Cancer Registry was used to identify patients with breast cancer. Patients with new-onset breast cancer from January 2007 to December 2015 were selected for this study and followed until December 31, 2017. Patients who were diagnosed with sleep disorders were set as the case group, and the controls were those without sleep disorders. We enrolled 5256 patients with sleep disorders and 10,512 patients without sleep disorders. There were 121 (2.30%) patients with ischemic stroke among the breast cancer patients with sleep disorders. The mean time from the diagnosis of breast cancer to the occurrence of ischemic stroke was 6.29±2.59 years for breast cancer patients with sleep disorders and 6.00±2.76 years for those without sleep disorders (p < 0.0001). After matching by age and index year, breast patients with sleep disorders had a 1.31-fold higher risk (95% confidence interval: 1.03-1.66; p-value=0.026) of ischemic stroke than those without sleep disorders, after adjustment for comorbidities, cancer clinical stage, and treatment types. In conclusion, Breast cancer patients with sleep disorders have an increased risk of stroke.

obot-assisted bilateral internal mammary arteries harvesting for off-pump coronary artery bypass grafting with 5 grafts by minimally invasive small incision: A case report / 中国胸心血管外科临床杂志

@#Objective    To introduce the method and preliminary experience of robot-assisted bilateral internal mammary arteries (BIMA) harvesting for off-pump coronary artery bypass grafting (OPCAB) with 5 grafts via left anterolateral minithoracotomy. Methods    BIMA were harvested using the da Vinci robotic surgical system, and the right internal mammary artery (RIMA) was pulled out of the thoracic cavity through right second intercostal space. Intercepting the distal part of the RIMA for the BIMA composite Lima-Rima Y graft and anastomosing the great saphenous vein with remaining RIMA end to end. The Y graft anastomosed with left anterior descending (LAD) branch and diagonal branches (DIAG), artery-vein graft sequentially anastomosed with blunt round branch, left ventricular posterior branch and posterior descending branch. Results    The operation succeeded without hemodynamic instability and intra aortic balloon pump (IABP) implantation or cardiopulmonary bypass. The blood flow of Y graft was 24 mL/min, and the blood flow of artery-vein graft was 30 mL/min. Ventilator assistance time was 35 hours, ICU staying time was 62 hours, and postoperative myocardial enzymes increased temporarily. Postoperative coronary CTA showed that all the grafts were patency, and cardiac ultrasound indicated that the heart function was normal. The patient cured and discharged from hospital 7 days after operation. Conclusion    Robot-assisted bilateral internal mammary artery harvesting for OPCAB with 5 grafts via left anterolateral minithoracotomy is feasible, which can achieve complete revascularization.

Comparative study on the perioperative results of different myocardial revasculariza-tion strategy in the treatment of elderly patients with coronary three-vessel disease / 中国胸心血管外科临床杂志

@#Objective    To compare the perioperative results of hybrid coronary revascularization (HCR), off-pump coronary artery bypass (OPCAB) and percutaneous coronary intervention (PCI) in elderly patients with three-vessel coronary artery disease involving left anterior descending (LAD) branch and explores the safety of surgery. Methods    We prospectively enrolled patients with coronary heart disease over 65 years who were admitted to General Hospital of People’s Liberation Army from January 2018 to September 2019. Coronary angiography results were all three-vessel lesions involving the anterior descending artery. After preoperative examination and assessment by the cardiovascular team, all patients were suitable for OPCAB or PCI treatment. According to the patient’s preference, HCR, OPCAB or PCI were performed. The preoperative baseline data and perioperative results were collected, and SPSS 22.0 was used for statistical analysis. Results    A total of 110 patients met the criteria and were included in the study, 28 in the HCR group, 45 in the OPCAB group, and 37 in the PCI group, with an average age of 71.4±5.6 years. There was no statistical difference in the preoperative baseline data of patients among the three groups. The intubation time (P=0.039), perioperative drainage volume (P<0.001), blood transfusion (P=0.021) in the HCR group were lower than those in the OPCAB group. There was no statistical difference in the main organ adverse events (MOAE, P=0.096) and in-hospital mortality (P=0.784) among the three groups of patients. The use of antibiotics in the PCI group was significantly lower than the other two groups (P<0.001). Conclusion    HCR combines the advantage of CABG and PCI including proved long-term patency rate with left internal mammary artery-LAD grafting, less trauma and superior long-term patency with PCI in non-LAD territory. Compared with OPCAB and PCI, there is no increase in perioperative major organ adverse events and in-hospital mortality. It is a safe and reliable minimally invasive myocardial revascularization technique for elderly patients with three-vessel coronary artery disease involving the anterior descending artery.

Effect of diabetes mellitus on long-term outcomes of surgical revascularization in patients with ischemic heart failure: a propensity score-matching study / 中华医学杂志(英文版)

BACKGROUND@#Diabetes mellitus (DM) is an important risk factor in the long-term outcomes of surgical revascularization. However, few studies have focused on patients with ischemic heart failure (IHF) and DM, and the results are controversial. This study aimed to evaluate the effect of DM on the long-term outcomes of IHF patients undergoing coronary artery bypass grafting (CABG).@*METHODS@#In this propensity-matched study, data of IHF patients who underwent CABG in our hospital from January 2007 to December 2017 were analyzed. With a mean 73-month follow-up time, the patients were divided into two groups according to whether they had DM. The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, stroke, recurrent myocardial infarction, and revascularization.@*RESULTS@#There was no significant difference in all-cause mortality between the two groups (5.8% vs. 4.1%, P = 0.216). The incidence of main adverse cardiovascular and cerebrovascular events (MACCE) in the secondary endpoint was significantly higher in the DM group than that in the non-DM group (10.4% vs. 8.1%, P = 0.023).@*CONCLUSIONS@#DM can negatively affect the long-term outcomes of IHF patients undergoing CABG by significantly increasing the overall incidence of MACCE, though the long-term survival does not show a significant difference between the DM and non-DM patients.

Practice Effects and Test-Retest Reliability of the Continuous Performance Test, Identical Pairs Version in Patients with Schizophrenia over Four Serial Assessments.

OBJECTIVE: The purposes of this study were to examine the practice effects and test-retest reliability of the Continuous Performance Test, Identical Pairs version (CPT-IP) over four serial assessments in patients with schizophrenia. METHOD: Fifty-six patients with schizophrenia were assessed with the CPT-IP four times, once per week. The CPT-IP contains four indices: "2-digit score," "3-digit score," "4-digit score," and "total score." RESULTS: The four indices showed trivial-to-small practice effects (Cohen's d = -0.13-0.24), good-to-excellent test-retest reliability (ICC = 0.62-0.88), and unacceptable random measurement error (MDC% = 33.8%-110.8%). CONCLUSIONS: The total score had the best reliability among the four indices. Although practice effects of the four indices all appeared cumulative, all four CPT-IP indices reached a plateau after the second assessment. These results indicate that clinicians should interpret the change scores of the CPT-IP conservatively and use the total-score index in their routine repeated assessments.

Outcomes of microsurgical clipping vs coil embolization for ruptured aneurysmal subarachnoid hemorrhage: A multicenter real-world analysis of 583 patients in China.

Aneurysmal subarachnoid hemorrhage (SAH) is a complex neurovascular syndrome with high disability and mortality. SAH patients may be managed with surgical clipping or coil embolization. In this study, we provided a real-world analysis of the outcome and prognostic factors of aneurysmal SAH in patients treated with coil embolization or microsurgical clipping.We retrospectively analyzed the medical records of aneurysmal SAH patients (n = 583) who underwent treatment at the First Hospital and the Second Hospital of Hebei Medical University, and Tangshan Worker's Hospital in China. All patients were evaluated by a combined neurosurgery and interventional neuroradiology team. Microsurgical aneurysmal clipping was performed using the skull base approach, while coil embolization was performed with bare platinum coils (with or without balloon assistance). The primary outcome was the Glasgow Outcome Scale (GOS) score at discharge.A total of 583 patients were included in this study, of which 397 (68.1%) of them underwent clipping and 186 (31.9%) received coil embolization. The patient cohort consisted of both poor grade and good grade aneurysmal SAH: 441 (75.6%) patients had good-grade (Hunt and Hess grade II or III) and 142 (24.4%) had poor grade (Hunt and Hess grade IV or V). Overall, 123 (21%) patients had unfavorable neurologic outcome (GOS score 1-3) and 460 (78.9%) patients had favorable neurologic outcome (GOS score 4 or 5). The mean GOS score at discharge was comparable for patients who underwent clipping and those received coil embolization (P > .05). Multivariate analysis showed that clipping only [OR (95%CI): 0.03 (0.01, 0.36); P = .000] and clipping with CSF drainage [OR (95%CI): 0.41 (0.18, 0.89); P = .001] were independent factors of a favorable outcome in patients with aneurysmal SAH. Coil embolization with hematoma removal [OR (95%CI): 0.03 (0.01, 0.36); P = .000] was also an independent determinant of a favorable outcome. High baseline Fisher grades were associated with significantly increased risk of an unfavorable outcome [OR (95%CI): 2.08 (1.30, 3.33); P = .002].Our findings suggested that both coil embolization and microsurgical clipping are viable treatment options for aneurysmal SAH patients. Procedures, such as CSF drainage and hematoma removal, performed in parallel with coil embolization and chipping should be considered when treating individual patients.

Regulatory Effect of Gandou Decoction on Wnt/β-catenin Signaling Pathway in Liver of Wilson Model Copper-loaded Rats / 中国实验方剂学杂志

Objective: To investigate the regulatory effect of Gandou decoction (GDD) on Wnt/β-catenin signaling pathway in hepatic tissue of Wilson disease model copper-loaded rats and its potential mechanism. Method: One hundred and fifteen SD rats were randomly divided into the normal group (n=20) and modeling group. Modeling group was given copper sulfate feed (1 g·kg-1·d-1) and 0.185%copper sulfate solution (0.02 mL·g-1·d-1) for 12 weeks after one week's adaptive feeding, so as to build the copper loaded rats model. After modeling, 95 model rats were randomly divided into model group (n=45), which were fed by modeling method for continuously four weeks; GDD group and penicillamine (PCA) group (n=25 per group). GDD group and PCA group were given GDD(0.4 g·kg-1·d-1) and PCA (0.09 g·kg-1·d-1) by gavage for four weeks. The hepatic tissues of rats in each group were removed after final medication for further research:inductively coupled plasma-atomic emission spectrometry(ICP-AES) was used to detect the content of Cu element in rat livers. Htoxylin eosin(HE) staining was used to detect the pathological changes of rat liver. Immunohistochemistry was used to detect expression of oxidative stress. Western blot was used to detect protein expressions in Wnt/β-catenin of rat livers. Result: Compared with model group, content of Cu element in GDD group was less (PPPβ-catenin, p-glycogen synthase kinase-3β(p-GSK3β),cellular myelocytomatosis oncogene (c-Myc) in GDD and PCA group increased, while p-β-catenin, Dishevelled3, GSK3β protein expressions reduced (PConclusion: GDD can relieve liver damage by promoting excessive copper discharge. GDD decoction can promote the compensatory self-healing of the injured liver tissue by activating Wnt/β-catenin signaling pathway in the hepatic tissue of Wilson disease model copper-loaded rats, so as to reduce the therapeutic effect of hepatocellular injury induced by high copper.

Effect of Gandou Decoction on Immune Function of Spleen in TX Mice of Wilson's Disease Model / 中国实验方剂学杂志

Objective: To discuss the effect of Gandou decoction (GDD) on the immune index of spleen in TX mice of Wilson's disease model. Method: The mice were divided into normal group, model group and GDD or tetrathiomolybdate(TM)treatment group, with 20 mice in each group. Each group was fed in various ways for 30 successive days. Normal group:10 normal DL mice were randomly selected and feed normally. Model group:20 TX mice were randomly selected and feed with 2 mL·kg-1·d-1ig saline by gavage twice per day. GDD or TM treatment group:80 TX mice were randomly selected and feed with 2 mL·kg-1·d-1 ig Gandou decoction 22,44,66 g·kg-1 or tetrathiomolybdate by gavage twice per day. ICP-MS was used to compare the expressions of trace elements inside the mice's spleens, flow cytometry was applied to detect the mice T lymphocyte subsets of splenic tissue CD4+, CD8+, CD4+/CD8+, and Western blot was used to detect the expressions of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-8 (IL-8), interleukin-17 (IL-17) and interleukin-18 (IL-18). Result: Flow ICP-MS results showed that GDD can reduce Cu of mice's spleen, flow cytometry results showed that CD4+and CD8+in model group were increased than those in normal group (P+/CD8+was decreased (P+and CD8+in middle and high-dose GDD groups were decreased (P+/CD8+was increased. According to Western blot detection, compared with normal group, the expressions of IL-2, IL-8, IL-17, IL-18, TNF-α and IFN-γ in the model group were increased (Pα, IFN-γ, IL-2, IL-8, IL-17 and IL-18 in the GDD middle and high or TM group were decreased (PPα in the GDD low were decreased (PConclusion: Spleen of TX mice shows the cellular immunity hyperfunction, which is mainly dominated by the negative immunoloregulation. GDD has a certain effect in regulating cellular immunity hyperfunctional state of TX mice, but it's difficult to thoroughly change the negative immune regulation.

Effect of Gandou Decoction on Autophagy of SH-SY5Y Cell Induced by High Copper and Its Mechanism / 中国实验方剂学杂志

Objective: To explore the effect of Gandou decoction on autophagy of SH-SY5Y cells induced by high copper and its mechanism, in order to provide new therapeutic targets and research ideas for the prevention and treatment of brain-type Wilson disease (WD) with traditional Chinese medicine. Method: CuSO4 model showed a certain dose-effect and time-effect relationship according to methyl thiazolyl tetrazolium(MTT); lactate dehydrogenase(LDH) leakage rate was detected by LDH release assay; flow cytometry method was used to detect intracellular reactive oxygen species (ROS) content. The fluorescent dye JC-1 was used to detect the mitochondrial membrane potential of the cells. Flow cytometry was used to quantify autophagy. The expressions of liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), microtubule-associated protein 1 light chain 3 (LC3A/B), mammalian target of rapamycin (mTOR) and UNC-51-like kinase-1 (ULK1), phosphorylation-ULK (p-ULK), phosphorylation-AMPK (p-AMPK) were detected by Western blot. Result: According to MTT results, CuSO4 showed a dose-effect and time-effect relationship with cells (P4, the survival rate of cells showed a downward trend (P4-induced cell death (P4 compared with the normal group (P4-injured cells (P4 significantly increased the production of ROS in cells (P4-induced intracellular ROS production (P4 induced a significant decrease in mitochondrial membrane potential in cells (P4-induced mitochondrial membrane potential in a dose-dependent manner (P1, AMPK, LC3A/B, ULK, p-AMPK in the model group were significantly increased, while the protein expressions of mTOR and p-ULK were significantly decreased (P1, AMPK, LC3A/B, p-AMPK and ULK were significantly decreased, whereas the protein expressions of mTOR and p-ULK were significantly increased in the rabbit serum group containing Gandou decoction (PConclusion: High copper can induce autophagic apoptosis in SH-SY5Y cells by inducing intracellular mitochondrial oxidative stress, up-regulating the expressions of autophagy-related proteins LKB1, AMPK, LC3A/B, ULK, p-AMPK and down-regulating the expressions of mTOR and p-ULK. However, Gandou decoction can inhibit the occurrence of autophagy, and cut off high copper-induced neuronal damage by down-regulating the expressions of autophagy-related proteins LKB1, AMPK, LC3A/B, ULK, p-AMPK, and up-regulating the expression of mTOR and p-ULK, so as to exert a neuroprotective effect.

Protective Effect of Gandou Decoction on Cer Signaling Pathway in HT-22 Induced by High Copper / 中国实验方剂学杂志

Objective: To detect ceramide(Cer) signaling pathway-related proteins expression levels in HT-22 with Gandou decoction (GDD), in order to explore its molecular targets and mechanism in regulating Cer signaling pathway. Method: The experiment was divided into normal group (normal HT-22 cultured by 10%blank rabbit serum), model group (HT-22 cells incubated with CuSO4), and GDD group (HT-22 cells incubated with CuSO4, continuously cultured by rabbit serum containing10%, 15%, 20%GDD). HT-22 cells were incubated with different concentrations of CuSO4.The cell growth and proliferation were assessed using methyl thiazolyl tetrazolium(MTT) method; flow cytometry was used to analyze the expression of reactive oxygen species (ROS); Western blot was used to detect relevant protein expression of Cer signaling pathway. Result: The results of MTT showed that CuSO4 inhibited the growth and proliferation of HT-22 cells in a time and concentration-dependent manner; flow cytometry results showed that the model group increased the release of ROS compared with the normal group (PPPPConclusion: High copper can induce oxidative stress and deactivate Cer signaling pathway, which led to hippocampal neuron injury. These findings suggest that GDD reduces neurotoxicity induced by copper overload by increasing the copper excretion that inhibits the expressions of ASM, Cer, p38 MAPK, Cyt C, Caspase-9, Caspase-3.GDD reduces neurotoxicity induced by copper overload by decreasing copper levels in brain and then regulating Cer signaling pathway.

Research Progress of Therapeutic Mechanism of Gandou Decoction in Treatment of Wilson's Disease / 中国实验方剂学杂志

Wilson disease (WD) is a treatable neurological inherited disorder characterized by copper metabolism impairment. Metal chelating drugs, such as penicillamine, have been used to treat WD for decades, is exposuring its limitations of effect and utilize sphere. Genetic therapy was considered as the most potential way of curing WD, is still can only be achieved in the laboratory, which have massive problems to solve before its clinical utilization. Based on this, we started to research the curative mechanism of traditional Chinese medicine(TCM) donated by national natural science fund project funding, found that TCM formula Gandou decoction regulate the metabolic disorders caused by liver cells and neurons apoptosis, autophagy, such as programmed cell death,from the molecular pathways of copper metabolism, Wnt/β-catenin pathway and mitogen-activated protein kmase(MAPK) pathways regulating liver damage such as cell signaling pathways, extracellular signal-regulated kinase(ERK) pathway and liver kinase B1(LKB1)/adenosine monophosphate activated protein kinase(AMPK) pathway and the cell signaling pathway of neuronal damage. The above experimental results were verified by TX mice, a reliable WD animal models. This paper aimed to systematically review the research of GDD therapeutic mechanisms from the sight of programmed cell death, including aptosis and autophagy, and provided theoretical for formula optimization. In addition, we elaborated some assumptions and feasible advice for the further research of GDD therapeutic mechanism.

Expression of peroxisome proliferator-activated receptor γ and uncoupling protein-1 after sleeve gastrectomy in obese diabetic rat / 中华内分泌外科杂志

Objective To investigate the expression of peroxisome proliferator-activated receptor γ (PPARγ) and uncoupling protein-1 (UCP-1) after sleeve gastrectomy in Zucker rats and to discuss the weight loss mechanisms.Metbods 30 male Zucker rats aged 10 weeks were randomly divided into 3 groups:the operation group (10 rats),the sham operation group(10 rats) and the diet-pairing group (10 rats).The rats were decapitated to retrieve the retroperitoneal adipose.mRNA and protein expressions of PPARγ and UCP-1 were detected by RT-PCR and Western blot.Results As for the operation group,the weight decreased significantly after the operation compared to the other two groups((250±5.8) g,(370±10.0) g,(310±9.6) g,respectively,P＜0.05).The expressions of PPARγ and UCP-1 gene of mRNA and protein were all significantly higher in the operation group (P＜0.05).Conclusions SG can up-regulate the expressions of thermogenic gene PPARγand UCP-1 in adipose in Zucker rats,browning the white adipose tissue,which was one of the important mechanisms of weight loss.