This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.

This article discusses the key pathogenesis of atherosclerosis （AS） based on the physiological characteristics and pathological changes of lipids and introduces the therapeutic effect of Zhuyuwan on AS， aiming to provide a theoretical basis for the treatment of cardiovascular diseases from the spleen. As essential substances， lipids have the same essence but different forms. They circulate throughout the body with body fluids under the action of Yang Qi to nourish the nutrient Qi and support the defensive Qi. Lipid metabolism disorder often leads to the obstruction of Qi movement， the accumulation of dampness and turbidity， and the generation of phlegm and blood stasis. It has been proven that the formation of vulnerable plaques in AS is attributed to the interaction of three pathogenic factors： deficiency of healthy Qi， phlegm-turbidity， and collateral stasis. Their pathological essence is closely related to abnormal lipid metabolism. As lipids constitute the thick and dense components of body fluids， their impaired dispersion may lead to phlegm-turbidity and blood stasis， the pathological process of which is predominantly ascribed to the dysfunction of the spleen in distributing essence. Therefore， AS is rooted in spleen-stomach disorder， manifests as plaques formed by pathological product accumulation in vessels， with lipid transport disorder as its core pathogenesis. Specifically speaking， the dysfunction of spleen in transportation with accumulation of dampness-turbidity marks the initial stage， and blood turbidity and coagulation and phlegm-nodules accumulating in vessels represent the intermediate phase. Cold accumulation and stagnated heat transforming into toxins represent the terminal stage. Zhuyuwan， first recorded in Taiping Holy Prescriptions for Universal Relief， contains equal proportions of Coptidis Rhizoma and Evodiae Fructus. Coptidis Rhizoma， bitter and cold， exerts descending and purging actions to assist stomach Qi in lowering turbidity. Evodiae Fructus， pungent-bitter and hot， disperses obstruction and promotes free flow to support spleen Qi in ascending the clear. The compatibility of Coptidis Rhizoma and Evodiae Fructus ascends the clear and descends the turbid to harmonize Yin and Yang， assisting the spleen in distributing essence and resolving lipid accumulation to reduce lipid levels. In terms of the therapeutic mechanism， Zhuyuwan modulates lipid metabolism by correcting immune-inflammation network imbalance， improving gut microbiota composition and metabolism， and enhancing reverse cholesterol transport. By analyzing the pathological characteristics of lipid transport disorder in AS， this study delves into the intrinsic connections between cardiovascular disease and lipid transport disorder， giving novel insights into the prevention and treatment of AS.

Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome， whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress， the nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine （TCM） to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients （including five types of compounds： flavonoids， terpenes， alkaloids， saponins， phenols） and 6 kinds of compound preparations （including three types of formulas： heat-clearing and detoxifying formulas， purgative formulas for promoting bowel movement， and formulas for reinforcing vital qi and consolidating the constitution） can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1， heme oxygenase-1， antioxidant response element and AMP-activated protein kinase， thereby alleviating sepsis-induced lung injury.

ObjectiveTo analyze the epidemiological and clinical characteristics of surveillance cases in a sentinel hospital for pertussis in Jiangxi Province in 2019, and to provide corresponding references for the prevention and control of pertussis. MethodsCase investigation of pertussis was conducted among sentinel hospital surveillance cases, collecting their basic information, epidemiological characteristics, clinical characteristics, and other information. ResultsA total of 125 pertussis surveillance cases were investigated in 2019, including 73 clinically diagnosed cases (58.40%) and 52 confirmed cases (41.60%). The age of onset was mainly concentrated in children under 5 years old (108 cases, 86.40%), with the largest number of cases in infants aged less than 1-year-old (48 cases, 38.40%). Most cases had a history of receiving pertussis vaccine before onset (110 cases, 88.00%), and the intervals between the onset date and the date of last dose of pertussis vaccine in the 1‒2 doses group were significantly shorter than that in the 3‒4 doses group (U=-5.990, P<0.001). Probable household transmission of pertussis was found in 3 cases. All cases had cough symptoms, mainly manifested as whooping cough (77 cases, 61.60%), in addition to other main clinical manifestations, such as fever (76 cases, 60.80%), vomiting (30 cases, 24.00%), conjunctival congestion (27 cases, 21.60%), and inspiratory whoop (16 cases, 12.80%). A total of 73 cases (58.40%) experienced complications, including 1 death case. All the cases had multiple medical visit experiences before this visit, with an interval of 2 (0,3) days between the onset date and the first visit date. The misdiagnosis rate at the first medical visit was 88.00% (110/125), and the misdiagnosis rate of the first visit in secondary and primary hospitals was significantly higher than that in tertiary hospitals, exhibiting a statistically significant difference (χ²=21.582, P<0.001). ConclusionThe clinical symptoms of pertussis cases are often atypical, and the first diagnosis is prone to misdiagnosis, so it’s necessary to further strengthen the early diagnosis capabilities for pertussis cases in healthcare institutions, especially in the primary healthcare institutions.

Background Exposure to ozone (O₃) is closely associated with an increased risk of mortality in the population, but this association exhibits regional heterogeneity, and relevant research in northern and central-western China is limited. Hohhot, as a typical city in the northern and western region, has seen a significant upward trend in O₃ concentrations (an increase of 17.9 μg·m⁻³ in 2020 compared to 2016). Studies targeting this region can fill the regional research gap. Objective To evaluate the health effects of ground-level O₃ exposure on resident mortality in Hohhot from 2018 to 2023. Methods Air quality, meteorological, and mortality data in Hohhot from 2018 to 2023 were collected. A time-series analysis based on Quasi-Poisson generalized additive model (GAM) was employed, controlling for meteorological factors, day-of-week effects, and holiday effects, to assess the impact of O₃ on non-accidental mortality, mortality from circulatory system diseases (CSD), and mortality from respiratory system diseases (RSD). Results From 2018 to 2023, the non-accidental, CSD, and RSD mortalities in Hohhot amounted to 89721, 47394, and 11378 cases, respectively. The daily maximum 8-hour average O₃ concentration (O₃-8 h) was 90.00 μg·m⁻³. According to the Class I limit (100 μg·m⁻³) of GB 3095—2012 Ambient Air Quality Standard, the annual average number of days exceeding the standard was 144 d. For single-day lag effects, O₃ had the strongest health impact on non-accidental mortality and CSD mortality on the current day (lag0), with effect sizes of 0.78% (95%CI: 0.33%, 1.24%) and 1.10% (95%CI: 0.50%, 1.71%), respectively. The strongest impact on RSD mortality occurred on the second day (lag2), with an effect size of 1.61% (95%CI: 0.61%, 2.62%). The subgroup analyses showed that for every 10 μg·m⁻³ increase in O₃-8 h concentration, the risk of non-accidental mortality in females increased by 0.70% (95%CI: 0.01%, 1.41%); for CSD mortality, the risk in males and individuals aged ≥65 years increased by 0.73% (95%CI: 0.01%, 1.47%) and 0.76% (95%CI: 0.13%, 1.39%), respectively. During the warm season, statistically significant risks were observed for non-accidental, CSD, and RSD mortalities, with increases of 1.07% (95%CI: 0.54%, 1.60%), 1.31% (95%CI: 0.59%, 2.04%), and 2.27% (95%CI: 1.07%, 3.49%), respectively. In the two-pollutant models incorporating sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), particulate matter with an aerodynamic diameter of 10 micrometers or less (PM₁₀), and fine particulate matter (PM_2.5), the effect estimates (excess risk) of O₃ remained stable and statistically significant (P<0.05), indicating model robustness. Conclusion Ground-level O₃ exposure in Hohhot increases mortalities due to non-accidental causes, CSD, and RSD, with more pronounced effects during the warm season. Females and individuals aged ≥65 years may be susceptible populations. Therefore, relevant authorities should prioritize the potential health risks of O₃ exposure, particularly to vulnerable groups, and promote targeted prevention and control strategies.

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.

Objective:To investigate the role and mechanism of N 6-methyladenosine (m 6A) methyltransferase-like 3 (METTL3) in vascular calcification (VC) of chronic kidney disease (CKD) through apoptosis-associated protein. Methods:(1) Real-time fluorescence quantitative PCR was used to test METTL3 mRNA in serum of maintenance hemodialysis (MHD) patients. (2) Western blotting was used to detect the expression of METTL3 protein in high-phosphorus stimulated vascular smooth muscle cells (VSMCs), and immunofluorescence double lable was used to observe the distribution of METTL3 and Runt-related transcription factor 2 (Runx2). The METTL3 overexpressed and knockdown plasmids were constructed and transfected into VSMCs. Alizarin red staining was used to detect calcification degree. Western blotting was used to detect the expressions of osteogenic markers [Runx2, bone morphogenetic protein-2(BMP-2), collagen Ⅰ] and apoptosis- related proteins Bax and Bcl-2. (3) SD rats were randomly divided into control group, CKD-VC group and S-adenosylhomocysteine (SAH) intervention group. The calcification of thoracic aorta was evaluated by von Kossa staining, and the protein expressions of Runx2, Bax and Bcl-2 were detected by immunohistochemistry and Western blotting.Results:(1) METTL3 mRNA expression in MHD patients with VC was significantly lower than that in non-VC patients ( P<0.05), and was negatively correlated with coronary artery calcium score ( r=-0.65, P<0.001). (2) The expression of METTL3 in VSMCs stimulated by high phosphorus was decreased and showed a time dependence. Immunofluorescence double label showed that METTL3 and Runx2 were co-expressed in the nucleus. METTL3 was overexpressed in high-phosphorus induced VSMCs, and the expressions of Runx2, collagen I and BMP-2 were significantly decreased, accompanied by the decrease of calcified nodules and Bax/Bcl-2 ratio (all P<0.05). Conversely, METTL3 knockdown aggravated VSMCs calcification by inducing apoptosis. (3) Furthermore, METTL3 inhibitor SAH was administered in vivo, and it was found that inhibition of METTL3 expression significantly increased the calcification of rat thoracic aorta, and the Bax/Bcl-2 ratio and Runx2 expression were up-regulated. Conclusions:Serum METTL3 level is reduced in MHD patients with VC. In vivo and in vitro studies demonstrate that METTL3 inhibits VC in CKD by mediating the apoptosis-related protein Bax/Bcl-2.

Objective:To assess the changes of selenium nutrition of school-age children in Kashin-Beck disease (KBD) areas of Linzhou County, Lhasa City and Xietongmen County, Shigatse City in Tibet Autonomous Region (referred to as Tibet), and provide a scientific basis for evaluating the effectiveness of prevention and control measures.Methods:According to the historical condition of KBD, a total of 344 children's hair samples were collected to determine the content of selenium in Kazi (KBD area) and Jiangxia townships (non-KBD area) of Linzhou County in 2013 and 2021, Renqinze (KBD area) and Tongmen townships (non-KBD area) of Xietongmen County in 2015 and 2021.Results:Compared to 2013/2015, in 2021, the hair selenium level of children in the four townships increased ( P < 0.001). The selenium nutritional level of more than 90% of the children reached medium or above (hair selenium > 0.25 μg/g) in 2021. The hair selenium levels of girls in the two KBD areas (Kazi and Renqinze townships) were lower than those of boys ( Z = - 2.83, - 2.83, P < 0.05). Conclusions:The selenium nutrition level of school-age children in KBD areas in Linzhou and Xietongmen counties has increased rapidly in recent years. However, the selenium nutrition level of girls is significantly lower than that of boys. It is necessary to strengthen prevention, controlling and monitoring, and to further improve the dietary structure of school-age children through the joint efforts of families and schools, to increase the proportion of exogenous high selenium food intake.