Development and Verification of a Traditional Chinese Medicine Diagnostic Scale for Type 2 Diabetes Mellitus with Turbid-Toxin Accumulation Syndrome / 中医杂志

To develop a traditional Chinese medicine （TCM） diagnostic scale for type 2 diabetes mellitus with turbid-toxin accumulation syndrome and to validate the performance of the scale. A candidate pool was established through literature review and expert consultation， and a clinical case information collection form was developed accordingly. Patients with type 2 diabetes mellitus admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from July 2021 to January 2022 were investigated， and 312 valid clinical case information collection forms were obtained， which were randomly divided into 235 cases in the study group and 77 cases in the validation group. Four statistical methods， namely， differentiation analysis， Cronbach's coefficient， correlation coefficient， and stepwise regression， were used to screen out the candidate items， and Logistic regression analysis and factor analysis were used to assign weights to the items， and the final diagnostic model was determined by the receiver operating characteristic （ROC） curve， and the diagnostic thresholds were calculated for the Yoden index. The final TCM diagnostic scale for type 2 diabetes mellitus was composed of 8 items： turbid dirt coating （with a weight value of 23， the same below）， sticky stools （16）， fullness in the epigastrium and abdomen （12）， dark complexion （12）， irritability （11）， brown spots on the skin （11）， heaviness of head （10）， and chest stuffiness （5）， and the degree score was 0， 0.5， 1.0， and 1.5 points corresponding to no， mild， moderate and severe symptoms， respectively. The total score was the sum of the degree score multiplied by the weighted value of each item， and when the total score reached 33 points， it is diagnosed as the turbid-toxin accumulation syndrome. The established scale was tested and evaluated in the study group and the validation group， and the results showed that the sensitivity of the study group and the validation group was 89.38% and 89.47%， with the specificity of 95.90% and 89.74%， the Yoden index of 0.85 and 0.79， the positive predictive value of 95.28% and 89.47%， the negative predictive value of 90.70% and 89.74%， the diagnostic advantage ratios of 198.18 and 72.67， and the Kappa values of 0.86 and 0.79， which indicated that the TCM diagnostic scale for turbid-toxin accumulation syndrome of type 2 diabetes mellitus showed good diagnostic ability.

Role of Ferroptosis in Bone Homeostasis and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Osteoporosis （OP） is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss， which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway， and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP， which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts， which is beneficial to maintain bone homeostasis， slow down the development process of OP， improve the clinical symptoms of patients， reduce the risk of disability， and improve their quality of life. However， there are few studies on ferroptosis in OP. Traditional Chinese medicine （TCM） is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP， with high safety， few toxic and side effects， and low treatment cost， and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis， discussed the role of ferroptosis in bone homeostasis， and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis， so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.

Relación entre biometría fetal, producto de acumulación de los lípidos y condición trófica al nacer / Relationship between fetal biometry, lipid accumulation product and the trophic condition at birth

Fundamento: Las alteraciones del estado nutricional materno generalmente se relacionan con desviaciones del crecimiento fetal, que pueden detectarse por los parámetros biofísicos fetales e identifican la posible condición trófica al nacer. Objetivo: Determinar la posible relación entre los parámetros biométricos fetales, la condición trófica al nacer y el producto de acumulación de los lípidos. Metodología: Se realizó un estudio transversal en el Policlínico Chiqui Gómez Lubian del municipio Santa Clara, durante el año 2019, en una población de 253 gestantes normopeso supuestamente sanas al inicio de la gestación. La muestra no probabilística fue de 144 gestantes. Las variables de estudio fueron: producto de acumulación de los lípidos, biometría fetal y condición trófica al nacer. Se utilizaron métodos teóricos, empíricos y estadísticos. Resultados: En el segundo trimestre ningún parámetro biométrico coincidió con la condición al nacer de pequeño, mientras que para el grande coincidieron las circunferencias cefálica y abdominal. En el tercer trimestre la longitud del fémur y la circunferencia abdominal coinciden en la identificación del pequeño y del grande. El PAL se correlacionó con la circunferencia abdominal del tercer trimestre y con el peso al nacer; presentando mayor frecuencia de valores en el tercer tertil para los nacimientos grandes. Conclusiones: La circunferencia abdominal fue el parámetro biométrico con mayor coincidencia con la condición trófica al nacer, la que se asoció con valores en el tercer tertil del PAL para la detección de nacimientos grandes, relacionándose el fenotipo normopeso metabólicamente obeso con el crecimiento fetal por exceso.

Background: Maternal nutritional status disorders are usually related to fetal growth deviations, which can be detected by fetal biophysical parameters and identify the possible trophic condition at birth. Objective: To determine the possible relationship between fetal biometric parameters, the birth trophic state and lipid accumulation product. Methodology: A cross-sectional study was conducted at the Chiqui Gómez Lubian Polyclinic in Santa Clara municipality, during 2019, in a population of 253 normal-weight pregnant women who were apparently healthy at the beginning of their gestation. The non-probability sample was made up of 144 pregnant women. Study variables were: lipid accumulation product, fetal biometry and trophic condition at birth. Theoretical, empirical and statistical methods were used. Results: In the second trimester, none of the biometric parameters matched the condition at birth as a small child, while in the large one the head and abdominal circumferences matched. In the third trimester, femoral length and abdominal circumference coincide in identifying the small one and the large one. LAP correlated with third trimester abdominal circumference and birth weight, presenting higher frequency of values in the third tertile for large births. Conclusions: Abdominal circumference was the biometric parameter with the highest coincidence with trophic condition at birth, associated with values in the third tertile of the LAP for detecting large births, relating the metabolically obese normal weight phenotype with excessive fetal growth.

α-Hederin Regulates SREBP1/FASN Pathway and Inhibits Malignant Phenotype of Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To explore the regulative effect of α-Hederin on the proliferation and invasion of NSCLC and investigate its related molecular mechanism. Methods After A549 and HCC-1833 cells were treated with a concentration gradient of α-Hederin for 24 and 48 h, the OD450nm was detected by using CCK8 assays, and the IC50 was calculated.The A549 and HCC-1833 cells were divided into the blank control and α-Hederin groups in accordance with IC50 values.Cell proliferation was detected by EdU assays, and cell cycle transformation and cell apoptosis were detected by flow cytometry.Cell mobility was detected by using Transwell and scratch assays.SREBP1 and FASN protein expression levels were detected through Western blot analysis, and cell lipid accumulation was detected via oil red O staining. Results The survival rate of lung cancer cells decreased significantly with the increase of α-Hederin concentration, and the IC50 values of A549 and HCC-1833 cells at 48 h were 15 and 25 μg/ml, respectively.Compared with the blank control group, cells proliferation and migration were significantly inhibited, cells were blocked in the G1/S phase, the apoptosis rate increased, and the protein expression and lipid accumulation of SREBP1/FASN significantly reduced after α-Hederin treatment. Conclusion α-Hederin can inhibit the proliferation and migration, G1/S phase transition and induce the apoptosis of NSCLC cells and hinder the malignant progression of NSCLC by downregulating the expression of SREBP1 and FASN and reducing the accumulation of cell lipids.

Alterations of gut microbiota composition and cogni-tive behavior in APP/PS1/tau triple-transgenic mouse model of Alzheimer's disease / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)is a progressive neurological disease.Given the important role of gut microbiota composition in AD pathology,the observed perturbation in the microbiota composition and diversity may serve as the mechanisms underlying age-dependent APP/PS1/tau triple-transgenic mouse(3×Tg-AD)mice amyloid deposition and memory deficits.Here-in,we intended to investigate the gut microbiota and as-sessed its relationship with the triggering and develop-ment of cognitive impairment of AD.METHODS This study involves the comparative assessment of spatial learning,amyloid β-protein(Aβ)accumulation,and fecal microbiota alterations in 3×Tg-AD mice from three age groups:AD asymptomatic stage(3 m),presymptomatic stage(6 m),and the symptomatic stage of AD(9 m).RE-SULTS We demonstrate that spatial memory deficits,brain Aβ accumulation,and weight gain in 3×Tg-AD mice gradually appear after 6 months of age.However,the total gut bacterial counts underwent changes from 3 to 6 months of age and were further altered at 9 months of age.Importantly,changes in gut bacteria abundance of Desulfobacterota and Actinobacteriota phylain 6-month-old mice preceded apparent spatial memory deficits.CONCLUSION Changes in the gut microbial community are one of the mechanisms of early AD pathology.

Association between long working hours and occupational stress/fatigue accumulation in medical staff of tertiary grade A hospitals in Shanghai / 环境与职业医学

Background Long working hours are a common occupational health risk factor. The problem of long working hours and its impact on health of medical staff cannot be ignored. Objective To investigate long working hours in medical staff of tertiary grade A hospitals in Shanghai, and evaluate the relationships of long working hours with occupational stress and fatigue accumulation. Methods A total of 1531 medical staff in departments of emergency, internal medicine, surgery, intensive care unit (ICU), anesthesiology, and obstetrics and gynecology from 6 hospitals in 6 districts of Shanghai were selected using stratified random sampling. A structured questionnaire was used to collect information on social demographics, occupational characteristics, andbehavior and lifestyle. The Core Occupational Stress Scale (COSS) and the Self-diagnostic Questionnaire on the Accumulation of Fatigue of Laborers were used to assess occupational stress and fatigue accumulation condition. Chi-square test and Kruskal-Wallis H test were used to analyze the distributions of long working hours, occupational stress, and fatigue accumulation, log-binomial models were used to analyze the relationships of long working hours with occupational stress and fatigue accumulation, and job title stratified models were also constructed. Results The average weekly working hours of the study subjects was (47.84±11.40) h, 65.90% of the medical staff worked more than 40 h every week. The percentages of the weekly working hours categories of 41-48 h, 49-54 h, and ≥55 h were 31.42%, 13.46%, and 21.03%, respectively. The positive rates of occupational stress and fatigue accumulation were 25.87% and 65.64% respectively, and the differences among different age, gender, job title, education, length of service, and shift system groups were statistically significant (P<0.05). The results of log-binomial regression showed that after adjusting for gender, age, monthly income, marital status, education, physical exercise, smoking, job position, length of service, and shift system, weekly working hours were an influencing factor of occupational stress and fatigue accumulation (P<0.05). Compared with weekly working hours≤40 h, the risk, PR(95%CI), of reporting occupational stress and fatigue accumulation increased to 2.595 (1.989, 3.385) and 1.578 (1.349, 1.845) times respectively for weekly working hours≥55 h (P<0.001). The results of job title stratification analysis showed that the risk of occupational stress among physicians, nurses, and medical technicians increased when weekly working hours≥55 h versus ≤40 h, and the PR (95%CI) values were 2.003 (1.383, 2.902), 1.971 (1.068, 3.636), and 2.770 (1.220, 6.288), respectively (P<0.05). The risk of fatigue accumulation was increased in physicians when weekly working hour≥55 h versus ≤40 h, with a PR (95%CI) value of 1.594 (1.208, 2.103) (P<0.001). Conclusion Long working hours are common among medical personnel and related to the occurrence of occupational stress and fatigue accumulation.

Reactivation of PPARα alleviates myocardial lipid accumulation and cardiac dysfunction by improving fatty acid β-oxidation in Dsg2-deficient arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM), a fatal heart disease characterized by fibroadipocytic replacement of cardiac myocytes, accounts for 20% of sudden cardiac death and lacks effective treatment. It is often caused by mutations in desmosome proteins, with Desmoglein-2 (DSG2) mutations as a common etiology. However, the mechanism underlying the accumulation of fibrofatty in ACM remains unknown, which impedes the development of curative treatment. Here we investigated the fat accumulation and the underlying mechanism in a mouse model of ACM induced by cardiac-specific knockout of Dsg2 (CS-Dsg2 -/-). Heart failure and cardiac lipid accumulation were observed in CS-Dsg2 -/- mice. We demonstrated that these phenotypes were caused by decline of fatty acid (FA) β-oxidation resulted from impaired mammalian target of rapamycin (mTOR) signaling. Rapamycin worsened while overexpression of mTOR and 4EBP1 rescued the FA β-oxidation pathway in CS-Dsg2 -/- mice. Reactivation of PPARα by fenofibrate or AAV9-Pparα significantly alleviated the lipid accumulation and restored cardiac function. Our results suggest that impaired mTOR-4EBP1-PPARα-dependent FA β-oxidation contributes to myocardial lipid accumulation in ACM and PPARα may be a potential target for curative treatment of ACM.

Discussion on the pathogenesis of "spleen deficiency and dampness accumulation" of colorectal polyps based on intestinal flora and glucose and lipid metabolism / 国际中医中药杂志

Intestinal flora imbalance and abnormal glucose and lipid metabolism are important risk factors and pathological mechanisms of colorectal polyps. "Spleen deficiency and dampness accumulation" is the core pathogenesis of colorectal polyps. The imbalance of intestinal flora is related to spleen deficiency, and the application of Chinese herbs for invigorating spleen is helpful to the recovery of intestinal flora balance. Abnormal glucose and lipid metabolism is related to dampness accumulation, and it is effective to treat it with bitter and spicy herbs or spleen-invigorating and dampness-eliminating herbs. The interaction between intestinal flora imbalance and abnormal glucose and lipid metabolism changes intestinal microenvironment, damages intestinal epithelial cells, causes abnormal proliferation of intestinal stem cells and leads to colorectal polyps, which is consistent with the pathogenesis of spleen deficiency and dampness accumulation in Traditional Chinese Medicine. Thus, we tried to explore the biological connotation of the pathogenesis of "spleen deficiency and dampness accumulation" of colorectal polyps from the perspective of the interaction of intestinal flora and glucose and lipid metabolism, in order to provide reference for identifying high-risk population and analyzing the therapeutic mechanism of compound prescription for invigorating spleen and removing dampness.

Methyl ferulic acid ameliorates ethanol-induced L02 cell steatosis through microRNA-378b-mediated CaMKK2-AMPK pathway / 中国中药杂志

Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 μmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.

Effect of VIT1/VIT2 overexpression on Fe and Cd accumulation in rice endosperm / 生物工程学报

Iron (Fe) deficiency and excess cadmium (Cd) in rice grain are important problems to be solved in agricultural production. Previous studies have shown that OsVIT1 and OsVIT2 are vacuolar iron transporters. In this study, wild-type ZH11 was selected as the background material and OsVIT1 and OsVIT2 were overexpressed in endosperm by using endosperm specific promoter Glb-1. Field experiments were conducted to study the effect of OsVIT1 and OsVIT2 overexpression on Fe and Cd accumulation in different parts of rice. The results showed that OsVIT1 overexpression in endosperm significantly reduced Fe content in grain by about 50%, while significantly increased zinc (Zn) and copper (Cu) contents in straw and Cu content in grain. OsVIT2 overexpression in endosperm significantly decreased Fe and Cd contents in grain by about 50%, and significantly increased Fe content in straw by 45%-120%. Overexpression of OsVIT1 and OsVIT2 in endosperm did not affect the agronomic traits of rice. In conclusion, OsVIT1 and OsVIT2 overexpression in endosperm reduced Fe accumulation in rice grain, which did not achieve the expected effect. OsVIT2 overexpression in endosperm also decreased Cd accumulation in grain and increased Fe accumulation in straw, which provided reference for iron biofortification and cadmium reduction in rice.

Shaoyaotang Alleviates Ulcerative Colitis by Regulating Th17/Treg Balance Through IL-6/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the role of interleukin-6 （IL-6）/signal transducer and activator of transcription 3 （STAT3） pathway in the balance of T helper 17 （Th17）/regulatory T （Treg） cells in ulcerative colitis （UC） with internal dampness-heat accumulation syndrome and the intervention mechanism of Shaoyaotang. MethodA total of 60 SD rats were randomized into blank group （equivalent volume of normal saline）， model group （equivalent volume of normal saline）， western medicine control group （0.42 g·kg-1 mesalazine）， and low-dose （11.1 g·kg-1）， medium-dose （22.2 g·kg-1）， and high-dose （44.4 g·kg-1） Shaoyaotang groups. UC with internal dampness-heat accumulation syndrome was induced in rats with the compound method except for the blank group. The administration lasted 14 days for each group. At 24 h after the last administration， rats were killed and the spleen and colon tissues were separated. The histopathological changes of colon were observed based on hematoxylin and eosin （HE） staining and the levels of interleukin-17 （IL-17） and transforming growth factor-β1 （TGF-β1） in colon tissue were detected by immunohistochemistry （IHC）. Flow cytometry was employed to determine the levels of Th17/Treg cells in the spleen， and Western blot to measure the levels of IL-6 and STAT3 proteins in colon tissue. ResultCompared with the blank group， the model group had lesions such as congestion and erosion， low percentage of spleen Treg cells （P<0.01）， high percentage of Th17 cells （P<0.01）， and high levels of IL-6 and STAT3 proteins in colon tissue （P<0.01）. Compared with the model group， the administration groups showed alleviation of colon injury， high percentage of spleen Treg cells （P<0.05， P<0.01）， low percentage of Th17 cells （P<0.01）， and low levels of IL-6 and STAT3 proteins in colon tissue （P<0.01）. ConclusionShaoyaotang regulates the balance of Th17/Treg by inhibiting the IL-6/STAT3 pathway， thereby relieving the pathological damage of UC rats with internal dampness-heat accumulation syndrome and affecting their immune function.

Pathophysiology of obesity and its associated diseases

The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that obesity strongly contributes to the development of cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on the public and on health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia and formation of visceral fat in other non-adipose tissues to evoke cardiovascular disease, liver diseases. Adipose tissue can also secrete adipokines and inflammatory cytokines to affect the local microenvironment, induce insulin resistance, hyperglycemia, and activate associated inflammatory signaling pathways. This further exacerbates the development and progression of obesity-associated diseases. Although some progress in the treatment of obesity has been achieved in preclinical and clinical studies, the progression and pathogenesis of obesity-induced diseases are complex and unclear. We still need to understand their links to better guide the treatment of obesity and associated diseases. In this review, we review the links between obesity and other diseases, with a view to improve the future management and treatment of obesity and its co-morbidities.

Iron accumulation and its impact on osteoporotic fractures in postmenopausal women / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.

Crise capitalista, política social e força de trabalho no Brasil / Capitalist crisis, social policy and labour power in Brazil

A partir de análises teóricas e estatísticas, objetivou-se apreender relações entre a política de assistência social e o processo de precarização da classe trabalhadora no atual contexto econômico e social brasileiro. Observa-se que o caráter compensatório das políticas de assistência social vem sendo acompanhado da precarização das condições de trabalho e da naturalização e da individualização do pauperismo, que mistificam os laços que conectam os usuários à sua classe social. Com isso, a aparente desconexão com a classe trabalhadora naturaliza a ausência de garantia do direito ao trabalho e potencializa a subsunção ao capital

Based on theoretical and statistical analyses, the objective was to apprehend relations between the social assistance policy and the process of precariousness of the working class, in the current Brazilian economic and social context. It ́s observed that the compensatory nature of social assistance policies is followed by the precariousness of working conditions and the naturalization and individualization of pauperism, which mystify the ties that connect the users to their social class. With this, the apparent disconnection with the working class naturalizes the lack of guarantee of the right to work and enhances the subordination to capital

Dominação burguesa entre o velho e o novo: a ascensão da extrema-direita no Brasil / Bourgeois domination between the old and the new: the rise of the extreme right in Brazil

Resumo: Este artigo tem como objetivo discutir o processo de ascensão da extrema-direita no Brasil, que culmina na vitória de Bolsonaro, e seu significado para a dinâmica de acumulação do capital. Em termos metodológicos, a pesquisa tem natureza qualitativa, de cunho bibliográfico, fundamentada no materialismo histórico-dialético, o qual permite capturar as múltiplas determinações do objeto sob um prisma de totalidade. Aponta como resultado que o bolsonarismo reatualiza a via autocrática de transformação capitalista no país, de modo a ajustar a dinâmica interna aos interesses de acumulação global do capital.

Abstract: This article aims to discuss the process of rise of the extreme right in Brazil, which culminates in Bolsonaro's victory, and its meaning for the dynamics of capital accumulation. In methodological terms, the research has a qualitative nature, of a bibliographic nature, based on historical-dialectic materialism, which allows capturing the multiple determinations of the object from a perspective of totality. It points out as a result that Bolsonarism re-updates the autocratic path of capitalist transformation in the country in order to adjust the internal dynamics to the interests of global capital accumulation.

L-carnitine reduces acute lung injury via mitochondria modulation and inflammation control in pulmonary macrophages

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a critical respiratory syndrome with limited effective interventions. Lung macrophages play a critical role in the pathogenesis of abnormal inflammatory response in the syndrome. Recently, impaired fatty acid oxidation (FAO), one of the key lipid metabolic signalings, was found to participate in the onset and development of various lung diseases, including ALI/ARDS. Lipid/fatty acid contents within mouse lungs were quantified using the Oil Red O staining. The protective effect of FAO activator L-carnitine (Lca, 50, 500, or 5 mg/mL) was evaluated by cell counting kit 8 (CCK-8) assay, real-time quantitative PCR (qPCR), ELISA, immunoblotting, fluorescence imaging, and fluorescence plate reader detection in lipopolysaccharide (LPS) (100 ng/mL)-stimulated THP-1-derived macrophages. The in vivo efficacy of Lca (300 mg/kg) was determined in a 10 mg/kg LPS-induced ALI mouse model. We found for the first time that lipid accumulation in pulmonary macrophages was significantly increased in a classical ALI murine model, which indicated disrupted FAO induced by LPS. Lca showed potent anti-inflammatory and antioxidative effects on THP-1 derived macrophages upon LPS stimulation. Mechanistically, Lca was able to maintain FAO, mitochondrial activity, and ameliorate mitochondrial dynamics. In the LPS-induced ALI mouse model, we further discovered that Lca inhibited neutrophilic inflammation and decreased diffuse damage, which might be due to the preservation of mitochondrial homeostasis. These results broadened our understanding of ALI/ARDS pathogenesis and provided a promising drug candidate for this syndrome.

Mechanism of Gegen Qinliantang in Improving Ectopic Lipid Accumulation in Liver of db/db Mice with Type 2 Diabetes Mellitus by Regulating AMPK-FoxO3a Autophagy Axis / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Gegen Qinliantang （GQT） in improving ectopic lipid accumulation in the liver of db/db mice with type 2 diabetes mellitus （T2DM） by regulating the adenosine monophosphate-activated protein kinase （AMPK）-forkhead box O3a （FoxO3a） autophagy axis， to provide a scientific basis for clarifying the hypoglycemic mechanism of GQT and its clinical application. MethodSeventy-five spontaneous T2DM db/db mice and 15 normal db/m mice were selected and maintained on a regular diet for one week， followed by the measurement of blood glucose. They were then randomly divided into six groups， with 15 mice in each group， including normal group （0.2 g·kg-1 saline）， metformin group （0.2 g·kg-1）， high-， medium， and low-dose GQT group （31.9， 19.1， 6.9 g·kg-1）， and model group （0.2 g·kg-1 saline）. The mice were orally administered the corresponding drugs once daily for 12 weeks. Fasting blood glucose （FBG） and glycated hemoglobin （HbA1c） were detected. Fasting insulin （FINS） and free fatty acid （FFA） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in liver tissues were observed by hematoxylin-eosin （HE） staining. The protein expression levels of phosphorylated （p）-AMPK， p-FoxO3a， and autophagy-related proteins microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ） and p62 were detected using Western blot. Immunofluorescence was used to detect the expression of hypoxia-inducible factor-1α （HIF-1α） in liver tissues. Real-time polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of AMPK， FoxO3a， and LC3 in liver tissues. ResultCompared with the normal group， the model group showed pathological changes in liver tissues， increased FBG， HbA1c， FINS， and FFA levels （P<0.01）， increased protein expression levels of p-AMPK， p62， and HIF-1α， decreased protein expression levels of p-FoxO3a and LC3Ⅱ in liver tissues （P<0.01）， decreased mRNA expression of AMPK， and increased expression of FoxO3a （P<0.01）. Compared with the model group， the treatment groups showed relieved liver tissue lesions and decreased FBG， HbA1c， FINS， and FFA levels （P<0.01）. The expression of p-AMPK， p62， and HIF-1α increased， while the expression of p-FoxO3a showed a dose-dependent decrease in the high-dose GQT group. The expression of LC3Ⅱ increased in the metformin group and the high-dose GQT group （P<0.01）. The mRNA expression of AMPK showed a dose-dependent increase， and the expression of FoxO3a showed a dose-dependent decrease in the treatment groups （P<0.01）. ConclusionGQT can improve ectopic lipid accumulation in the liver of T2DM db/db mice， which may be related to the regulation of the AMPK-FoxO3a autophagy axis.

Study on the mechanism of Yishen tongluo formula improving abnormal lipid metabolism based on SREBPs pathway / 中国药房

OBJECTIVE To explore the mechanism of Yishen tongluo formula （YSTLF） in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins （SREBPs） pathway. METHODS Using C57BLKS/J （db/db） mice as model and C57BLKS/J （db/m） mice as normal control， the mechanism of 1， 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient， the contents of serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL） and high-density lipoprotein （HDL）， observing steatosis and lipid accumulation in liver tissue of mice， detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c， Srebp-2 and their downstream lipid metabolism-related target genes （Fasn， Acc1， Scd5， Fads1， Hmgcr， Dhcr24， Insig-1， Fdps） in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism， and 25-HC （SREBPs inhibitor， 10 μmol/L） as the control， the effects of 125， 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c， SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1， 2.5， 5 g/kg YSTLF significantly reduced the levels of TC， TG and LDL， the percentage of lipid droplet-positive region in liver tissue and liver coefficient， significantly down-regulated protein expressions of Pre-SREBP-1， n-SREBP-1， Pre-SREBP-2 and n-SREBP-2， and mRNA transcription of Srebp-1c， Srebp-2 and their downstream target genes in liver tissue， while significantly increased HDL level， with statistical significance （P＜0.05 or P＜0.01）. In the cell experiment in vitro， the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125， 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment； there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250， 500 μg/mL YSTLF groups （P＞0.05）. CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs， so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes， promote the degradation of TC and TG， improve the abnormality of lipid metabolism and inhibit lipid accumulation， thus playing the role of lipid-lowering.

Effect of Modified Gualou Zhishitang Combined with Piperacillin Sodium and Tazobactam Sodium on Immune Function and Serum Levels of Inflammatory Cytokines in Patients with Stroke-associated Pneumonia with Syndrome of Phlegm-heat Accumulation in Lung / 中国实验方剂学杂志

ObjectiveTo explore the effects of modified Gualou Zhishitang combined with piperacillin sodium and tazobactam sodium on the immune function and serum levels of inflammatory cytokines in the patients with stroke-associated pneumonia （SAP， syndrome of phlegm-heat accumulation in lung）. MethodEighty SAP patients with the syndrome of phlegm-heat accumulation in lung were randomized into a control group （40 cases） and a study group （40 cases）. The SAP patients in the control group were treated with piperacillin sodium and tazobtam sodium， while those in the study group were treated with modified Gualou Zhishitang on the basis of the treatment in the control group for 2 consecutive weeks. The clinical therapeutic effects， immune function indexes， inflammation indexes， and lung function of SAP patients in the two groups before and after treatment were determined and compared. ResultAfter treatment， the scores of lesion， pulmonary rales， cough， fever， phlegm color， and constipation in both groups decreased （P<0.05）. After treatment， the ratio of forced expiratory volume in the first second to forced expiratory volume （FEV1/FVC） and forced expiratory volume in the first second as percentage of predicted value（FEV1%） in both groups improved （P<0.05）， and the study group outperformed the control group （P<0.05）. The treatment decreased the neutrophil to lymphocyte ratio （NLR） in the two groups （P<0.05）， and the study group had lower NLR than the control group after treatment （P<0.05）. The serum levels of procalcitonin （PCT） and hypersensitive C-reactive protein （hs-CRP） in both groups declined after treatment （P<0.05）， and the declines were more significant in the study group than in the control group （P<0.05）. After treatment， the study group was better than the control group （P<0.05）. The treatment in both groups elevated the levels of CD3+， CD4+， and CD4+/CD8+ in the peripheral blood and lowered the level of CD8+ （P<0.05）， and the changes were more significant in the study group than in the control group （P<0.05）. The total response rate of the study group was 95.00% （38/40）， which was higher than that （80.00%， 32/40） of the control group （χ2=4.114，P<0.05）. There was no significant difference in the incidence of adverse reactions between the two groups. ConclusionModified Gualhou Zhishitang combined with piperacillin sodium and tazobactam sodium demonstrates a significant therapeutic effect on the SAP patients with the syndrome of phlegm-heat accumulation in lung. This therapy can mitigate the clinical symptoms， improve the lung function， lower the serum levels of inflammatory cytokines， and improve the immune capacity， with high safety.

Association of cardiometabolic index and lipid accumulation product with hypertension prevalence in adults in Pingshan District, Shenzhen / 公共卫生与预防医学

Objective To explore the association of (cardiometabolic index , CMI ) and ( lipid accumulation product , LAP ) with the prevalence of hypertension in adults in Pingshan District, Shenzhen, and to evaluate the predictive value of CMI and LAP for the prevalence of hypertension. Methods A cross-sectional survey was conducted, in which 1000 permanent residents aged 18-69 years in Pingshan District, Shenzhen were randomly selected as survey subjects. The data were collected using questionnaires, physical measurements and blood tests, and the relationship between CMI, LAP and hypertension prevalence was analyzed using logistic regression models. Results A total of 987 subjects were included in the analysis, including 471 (47.72%) males and 516 (52.28%) females, with an average age of 40.9 ± 11.1 years. Subjects of different genders were divided into groups Q1 to Q4 according to quartiles of CMI and LAP, and the prevalence of hypertension increased with increasing levels of CMI and LAP in both men and women (P for trend < 0.001). Logistic regression analysis revealed that after adjusting for variables such as age and occupation, the OR for hypertension was 1.251 (1.025-1.526) and 1.685 (1.001-2.836) for men and women, respectively, for each standard deviation increase in CMI; the OR for hypertension was 3.519 (1.343-9.222) for men in the Q4 group, compared to the CMI subgroup Q1. For each standard deviation increase in LAP, the ORs for hypertension were 1.355 (1.089-1.686) and 1.825 (1.023-3.254) for men and women, respectively; compared to LAP subgroup Q1, the ORs for hypertension in the male Q3 and Q4 groups were 2.554 (1.103-5.909) and 5.322 (2.393-11.834), while the OR for hypertension in the female Q4 group was 2.906 (1.096-7.703). ROC analysis revealed that the area under the curve (AUC) for CMI, LAP, and BMI was 0.671, 0.704, and 0.702 for males, and 0.660, 0.722, and 0.697 for females, respectively. The AUC for LAP was greater than that for CMI for different genders (P < 0.01). Conclusion The greater the CMI and LAP values in adults in Pingshan District, Shenzhen , the higher the prevalence of hypertension. CMI and LAP have certain values in predicting the prevalence of hypertension.