Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

OBJECTIVE To analyze the current situation of drug use in domestic aeromedical rescue， and provide references for the development of aeromedical rescue services and the rational use of drugs on board. METHODS All literature on aeromedical rescue in China were retrieved from the databases of SinoMed， CNKI， VIP， and Wanfang data up to September 1st， 2024. Extracting descriptive analysis were conducted on the literature screened by the inclusion and exclusion criteria. RESULTS A total of 36 literature were included. Aeromedical rescue cases had been reported in China since 1985， with a cumulative total of 5 370 cases reported. Prehospital rescue performed 861 cases， with 96.40% of them involving the use of at least 9 categories， totaling at least 10 different drugs， primarily emergency drugs. Interhospital rescue performed 4 509 cases， and 85.23% of them used over 48 kinds of drugs across 19 categories， mainly emergency drugs supplemented by specialty drugs. From the view of transportation， 5 166 air transfers were made by helicopters， of which 88.00% involved the use of drugs， and 204 cases by fixed-wing aircraft， of which 91.18% involved the use of drugs. CONCLUSIONS Drugs are frequently used in aeromedical rescue involving a wide variety of types in China. It is imperative to strengthen the focus on the equipment and rational use of drugs in aeromedical rescue， thereby facilitating the establishment of a standardized theoretical framework.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Objective To investigate the effect of field angle on the results of in vivo dose validation of electronic portal imaging device(EPID)in patients.Methods Design the mold test and analyze the influence of different mold thicknesses and different frame angles on the 2D γ pass rate.Twenty-three patients who un-derwent radiotherapy in the Department of Radiotherapy of Jinhua Municipal Central Hospital from January to June 2023 were selected as the research object.In vivo dose verification was carried out during treatment to obtain 2D γ pass rate using same-day sector beam CT(FBCT)of planned CT and executive image guided(IG-RT)as reference images,and the influence of field angle on pass rate was analyzed.Results When the frame angle was unchanged,the area of the shooting field was larger than 17 cm×17 cm,and the 2D γ passing rate decreased with the increase of the thickness.The frame angle had no effect on the 2D γ pass rate when the mold thickness was constant.In clinical treatment data,the passage rate of 2D γ near 0°/180° was higher than that near 90°/270°(P＜0.05),and the passage rate near 90°/270° in the FBCT group was higher than that in the IGRT group(P＜0.05).The median passing rate of 3 mm 2D γ was 97.97％in 3％of the 23 patients.The non-IGRT group was 96.81％,the IGRT group was 97.89％,the FBCT group was 98.94％.There was a statistically significant difference in 2D γ passing rate between the non-IGRT group and the IGRT group(Z=-5.083,P＜0.05),and there was a statistically significant difference in 2D γ passing rate between the IGRT group and the FBCT group(Z=-10.657,P＜0.05).Conclusion Clinically,the difference of pass rate in vi-vo dose verification at different rack angles is mainly due to the difference of images within and between ses-sions.Using same-day FBCT as the reference image for in-vivo dose verification can improve the accuracy of pass rate and eliminate the influence of image difference between sessions.

Objective To investigate the therapeutic mechanism of Dingkun Dan(DKD)in polycystic ovary syndrome(PCOS)by examining the effects of microRNA-30d-5p on ovarian granulosa cells(GCs).Methods A PCOS rat model was established using dehydroepiandrosterone(DHEA).Normal rat GCs and PCOS rat GCs were cultured in vitro and divided into four groups:blank control group,model group,low-dose DKD group,and high-dose DKD group.After grouping,GCs viability was assessed using the methyl thiazolyl tetrazolium(MTT)assay,GCs apoptosis was analyzed by flow cytometry,and the gene expression of transforming growth factor β1(TGF-β1),Smad2,Smad3,and microRNA-30d-5p in GCs was measured by real-time polymerase chain reaction(RT-PCR),protein expression of TGF-β1,Smad2,and Smad3 in GCs was detected by Western Blot.Results Compared with the blank control group,the model group exhibited significantly decreased GCs viability,increased GCs apoptosis,upregulated mRNA and protein expression of TGF-β1,Smad2,and Smad3,and downregulated microRNA-30d-5p expression,the differences were statistically significant(P＜0.01).Compared with the model group,both low-and high-dose DKD groups showed increased GCs viability,reduced GCs apoptosis,downregulated mRNA and protein levels of TGF-β1 Smad2 and Smad3,elevated microRNA-30d-5p expression,and the differences were statistically significant(P＜0.05 or P＜0.01).Conclusion DKD promotes GCs proliferation by targeting Smad2 via microRNA-30d-5p,suggesting a potential therapeutic role in PCOS-related ovulatory dysfunction.

OBJECTIVE To explore the practicality of the pharmaceutical pathway for prophylactic use of antibiotics during the perioperative period of class Ⅰ neurosurgery incisions. METHODS The previously established pharmaceutical pathway for the prophylactic use of antibiotics in the perioperative period of class Ⅰ neurosurgery incisions was used to retrospectively evaluate the prophylactic use of antibiotics in 127 cases. The “antibiotics prophylactic use scoring system” in the pharmaceutical pathway was used to conduct preoperative scoring， and the patient’s actual antibiotics use was compared and analyzed in combination with existing Guiding Principles for Clinical Application of Antibiotics （2015 Edition） （hereinafter referred to as the Guiding Principles）. The pharmaceutical pathway also innovatively proposes key points for improvement in terms of the frequency of adding antibiotics during surgery and the duration of prophylactic use of antibiotics after surgery. By comparing with the actual medication situation of patients， the direction for updating the Guiding Principles was explored. RESULTS According to the retrospective analysis results， for neurosurgery class Ⅰ incision surgery， in addition to the preoperative prophylactic use of antibacterial drugs for skull mass resection and carotid endarterectomy recommended in the guidelines， endoscopic trigeminal microvascular decompression， arthroscopy and other specific joint examinations， spinal nerve Radical decompression， endoscopic lumbar nucleectomy， dural repair， and spinal canal decompression can also be further explored about the situation of not using antibacterial prophylaxis before surgery； at the same time， for the patients undergoing class Ⅰ neurosurgery incisions， the use of antibiotics during and after surgery may be considered for a second addition of antibiotics， taking into account the surgical time. If cerebrospinal fluid leakage occurred after surgery， it is recommended to extend the duration of prophylactic use of antibiotics appropriately. CONCLUSIONS The application of pharmaceutical pathways can provide more targeted analysis of key points in the prevention of antibiotic use， which promotes the transformation of perioperative antibiotics management for class Ⅰ incisions from “qualitative， empirical” management to “quantitative， scientific” management.

【Objective】 To explore lifestyle patterns among Chinese preschool school children by latent class analysis, and to analyze its associations with behavior problems from person-centered perspective, in order to provide theoretical reference for improving children′s mental health. 【Methods】 A questionnaire survey was conducted among parents of children aged 3 - 6 years old in five kindergartens in Xuzhou city by cluster sampling from April to May 2021.The survey content included the demographic characteristics, rearing environment, life behaviors and behavior problems, which was measured by Strengths and Difficulties Questionnaire(SDQ). Latent class analysis was used to explore latent lifestyle patterns.Unadjusted and adjusted Logistic regression analysis was used to test the associations between latent lifestyle patterns and behavior problems. 【Results】 The sample size was 1 190, including 618 (51.9%) boys.Latent class analysis for 7 life behaviors showed that three latent class model was the best one: low-risk group (206, 17.3%), medium-risk group (721, 60.6%) and high-risk group (263, 22.1%).After controlling demographic factors, adjusted Logistic regression model showed that compared to low-risk group, children in high-risk group had more risks of developing hyperactivity (OR=2.129, 95%CI: 1.230 - 3.685), peer problems (OR=2.051, 95%CI: 1.316 - 3.197), and total difficulties (OR=2.081, 95%CI: 1.290 - 3.356). 【Conclusions】 Improper dietary balance and irrational structure of daily activities substantially escalate the risk of emotional and behavioral issues in preschool-age children.Helping preschool children form a healthy lifestyle pattern is conducive to preventing behavioral problems.