Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment， diet， and lifestyle， which is closely related to many diseases in modern medicine， such as hyperlipidemia， obesity， fatty liver， atherosclerosis， metabolic syndrome， and cardiovascular and cerebrovascular diseases， with a wide range of influence and far-reaching harm. According to the Huangdi Neijing， lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids， which has the function of nourishing， and it is the initial state and source of important substances in the human body such as brain， marrow， essence， and blood. Once the grease of the human body is abnormal， it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach， which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments， leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity， which accumulates in the body's meridians， blood vessels， skin pores， and organs， forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays， it was divided into four common pathogenesis types： ''inability to distinguish between the clear and turbid， turbid stagnation in the Ying blood''， ''spleen not rising clear， turbid accumulation in the vessels''， ''spleen dysfunction， lipid retention in the pores''， ''spleen failure to transportation and transformation， and grease accumulation in the liver''. According to the pathogenesis， it could be divided into four common syndromes， namely， turbid stagnation in the Ying blood， turbid accumulation in the vessels， lipid retention in the pores， and grease accumulation in the liver， and the corresponding prescriptions were given for syndrome differentiation and treatment， so as to guide clinical differentiation and treatment of the lipid turbidity disease.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

Background The Inner Mongolia Autonomous Region is a vast area with a wide array of ecological environments, resulting in considerable regional variations in air pollution characteristics. Current research is limited by a scarcity of systematic, region-wide studies and risk assessments. Objective To assess the health risks associated with inhalation exposure to nine heavy metal and metalloid elements in atmospheric fine particulate matter (PM_2.5) for the population of the Inner Mongolia Autonomous Region. Methods From the 10th to the 16th of each month throughout 2023, atmospheric PM_2.5 samples were collected at designated monitoring sites in 12 leagues (cities) across the Inner Mongolia Autonomous Region to analyze the characteristics and trends in concentration. The health risk assessment model developed by the United States Environmental Protection Agency was employed to evaluate both the non-carcinogenic and carcinogenic risks associated with the heavy metal elements beryllium (Be), cadmium (Cd), chromium (Cr), hydrargyrum (Hg), plumbum (Pb), manganese (Mn), and nickel (Ni) and the metalloid elements stibium (Sb) and arsenic (As). Results In 2023, a total of 1206 valid PM_2.5 samples were analyzed from the Inner Mongolia Autonomous Region. The annual average PM_2.5 concentrations in Inner Mongolia, as well as in the cities of Ordos, Wuhai, and the Alxa League, all exceeded the national limit of 35 μg·m⁻³. The PM_2.5 concentrations across the leagues (cities) exhibited a clear seasonal variation, peaking in winter, followed by spring, and reaching a minimum in summer and autumn. The median PM_2.5 concentration in Ordos throughout the year was higher than that in the other leagues (cities) of the region. Concerning health risks, the non-carcinogenic risks associated with the 9 elements detected in each league (city) were all below 1, indicating acceptable levels. However, the non-carcinogenic risk values for Mn, Cr, and As were relatively high; specifically, Ordos City displayed the highest non-carcinogenic risk values for Mn (7.74×10⁻¹) and Cr (2.97×10⁻²), while Chifeng City recorded the highest value for As (2.34×10⁻³). The carcinogenic risk values for As, Cd, Cr, and Ni fell within the range of 1×10⁻⁹ to 1×10⁻⁵, representing an acceptable level. The health risks varied with age, and the elderly residents faced the highest non-carcinogenic and carcinogenic health risks. Conclusion While the carcinogenic and non-carcinogenic risks from heavy metals and metalloids within atmospheric PM_2.5 in the Inner Mongolia Autonomous Region are generally within acceptable limits, the potential risks that Mn, As, and Cr pose to the health of elderly people warrants particular attention, and Ordos and Chifeng cities exhibit notably higher health risks among other areas. It is recommended that regular, long-term monitoring be conducted, taking into account the specific conditions at monitoring sites across each league (city), and that targeted air quality management strategies be implemented to protect public health.

OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Objective:To investigate the metabolism-related proteins and their presence in the plasma of female androgenetic alopecia (FAGA) patients.Methods:From March 2021 to March 2023, FAGA patients aged 18-50 (FAGA group) and healthy women (HC group) were recruited from the Dermatology Outpatient Department of Huashan Hospital. 3 ml of peripheral venous blood was collected from each participant and centrifuged to obtain plasma. Olink proteomics analysis was performed on the collected plasma, differentially expressed proteins were screened with R language, the diagnostic accuracy of the differentially expressed proteins was assessed using receiver operating characteristic (ROC) curve. Gene ontology (GO) analysis was performed on differentially expressed proteins. Immunofluorescence analysis on hair follicles in the parietal region of the FAGA group and the occipital region of the HC group was performed to validate the differentially expressed proteins identified. SPSS 25.0 software was used to analyze the data, with normal distribution metric data represented by Mean±SD. Student’s t-test was used to compare the basic information of two groups of subjects and the relative fluorescence intensity of differentially expressed proteins in hair follicles. Pearson correlation analysis was performed on plasma metabolism-related proteins and the basic information of subjects. P<0.05 indicates a statistically significant difference. Results:Sixty-one cases were included in the FAGA group, with an average age of (33.8±7.4) years and an onset age of (29.5±7.8) years. Among them, 38 cases were mild FAGA, 14 cases were moderate, and 9 cases were severe. Twenty-seven cases were included in the HC group, with an average age of (32.0±7.7) years. There was no statistically significant difference in the basic information (age, body mass index, testosterone, 25-hydroxyvitamin D, uric acid, and ferritin levels) between the two groups of subjects ( P>0.05). Compared to the HC group, the plasma of the FAGA group showed 26 significantly upregulated differentially expressed proteins ( P<0.05), with AHCY and NECTIN2 exhibiting the most significant differences (all P=0.003). The ROC curve evaluation revealed that the area under the curve for AHCY and NECTIN2 was greater than 0.7, indicating good diagnostic accuracy. The GO analysis revealed that the differentially expressed proteins were primarily enriched in the BAT3 complex (cellular component), ubiquitin-dependent ERAD pathway, natural killer cell activation (biological process), as well as ubiquitin protein ligase binding and ubiquitin-specific protease binding (molecular function). Pearson correlation analysis revealed that AHCY ( r=-0.23, P=0.010) and NECTIN2 ( r=-0.31, P=0.033) were negatively correlated with the severity of hair loss in FAGA patients. The results of hair follicle immunofluorescence analysis showed that the relative fluorescence intensity of AHCY and NECTIN2 in the FAGA group was higher than that in the HC group ( P<0.05). In other words, both AHCY and NECTIN2 were upregulated in the FAGA group. Conclusion:Metabolism-related proteins play an important role in FAGA. AHCY and NECTIN2 may serve as early diagnostic biomarkers for FAGA.

Objective:To investigate the metabolism-related proteins and their presence in the plasma of female androgenetic alopecia (FAGA) patients.Methods:From March 2021 to March 2023, FAGA patients aged 18-50 (FAGA group) and healthy women (HC group) were recruited from the Dermatology Outpatient Department of Huashan Hospital. 3 ml of peripheral venous blood was collected from each participant and centrifuged to obtain plasma. Olink proteomics analysis was performed on the collected plasma, differentially expressed proteins were screened with R language, the diagnostic accuracy of the differentially expressed proteins was assessed using receiver operating characteristic (ROC) curve. Gene ontology (GO) analysis was performed on differentially expressed proteins. Immunofluorescence analysis on hair follicles in the parietal region of the FAGA group and the occipital region of the HC group was performed to validate the differentially expressed proteins identified. SPSS 25.0 software was used to analyze the data, with normal distribution metric data represented by Mean±SD. Student’s t-test was used to compare the basic information of two groups of subjects and the relative fluorescence intensity of differentially expressed proteins in hair follicles. Pearson correlation analysis was performed on plasma metabolism-related proteins and the basic information of subjects. P<0.05 indicates a statistically significant difference. Results:Sixty-one cases were included in the FAGA group, with an average age of (33.8±7.4) years and an onset age of (29.5±7.8) years. Among them, 38 cases were mild FAGA, 14 cases were moderate, and 9 cases were severe. Twenty-seven cases were included in the HC group, with an average age of (32.0±7.7) years. There was no statistically significant difference in the basic information (age, body mass index, testosterone, 25-hydroxyvitamin D, uric acid, and ferritin levels) between the two groups of subjects ( P>0.05). Compared to the HC group, the plasma of the FAGA group showed 26 significantly upregulated differentially expressed proteins ( P<0.05), with AHCY and NECTIN2 exhibiting the most significant differences (all P=0.003). The ROC curve evaluation revealed that the area under the curve for AHCY and NECTIN2 was greater than 0.7, indicating good diagnostic accuracy. The GO analysis revealed that the differentially expressed proteins were primarily enriched in the BAT3 complex (cellular component), ubiquitin-dependent ERAD pathway, natural killer cell activation (biological process), as well as ubiquitin protein ligase binding and ubiquitin-specific protease binding (molecular function). Pearson correlation analysis revealed that AHCY ( r=-0.23, P=0.010) and NECTIN2 ( r=-0.31, P=0.033) were negatively correlated with the severity of hair loss in FAGA patients. The results of hair follicle immunofluorescence analysis showed that the relative fluorescence intensity of AHCY and NECTIN2 in the FAGA group was higher than that in the HC group ( P<0.05). In other words, both AHCY and NECTIN2 were upregulated in the FAGA group. Conclusion:Metabolism-related proteins play an important role in FAGA. AHCY and NECTIN2 may serve as early diagnostic biomarkers for FAGA.