ObjectiveTo observe the protective effect of Erchentang （ECT） on SiO₂-induced lung injury in rats and to explore its underlying mechanism. MethodsA rat model of lung injury was established by a single intratracheal instillation of 50 mg·mL^-1 SiO₂ suspension. Thirty male Sprague-Dawley （SD） rats were randomly assigned to five groups： control， model， low and high-dose （4.5 g·kg^-1·d^-1 and 9 g·kg^-1·d^-1， respectively） ECT， and dexamethasone （0.2 mg·kg^-1·d^-1）. All the groups were treated for 4 consecutive weeks. Histopathological alterations in the lung tissue were examined by hematoxylin and eosin （HE） staining. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue were measured through biochemical assays. The expression of key molecules in the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway was determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， Western blot， and immunofluorescence assay. The primary active components of ECT were identified by ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and their binding affinity to Nrf2/HO-1 was assessed by molecular docking. Untargeted metabolomics of the lung tissue was performed based on UPLC-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and correlation analysis was performed to identify differential metabolites and parameters closely associated with the Nrf2/HO-1 pathway. ResultsCompared with the control group， the model group exhibited a reduction in body weight gain， an increase in lung index， increased MDA content， weakened SOD and GSH-Px activities in the lung tissue， down-regulated mRNA and protein levels of Nrf2 and protein levels of HO-1 and GPX4， and an up-regulated protein level of Keap1 （P<0.05， P<0.01）. Treatment with ECT attenuated the SiO₂-induced decline in body weight （P<0.05）， alleviated inflammatory cell infiltration and silicotic nodule formation in alveoli， and reduced the MDA content and enhanced the SOD and GSH-Px activities in the lung tissue （P<0.05， P<0.01）. UPLC-MS/MS and molecular docking revealed that core components of ECT， such as hesperidin and glycyrrhizic acid， displayed strong binding affinity to Nrf2/HO-1. Molecular biological experiments demonstrated that ECT promoted nuclear translocation of Nrf2， up-regulated the mRNA and protein levels of HO-1 and GPX4， and down-regulated Keap1 expression （P<0.05， P<0.01）. Metabolomic analysis indicated that ECT reversed the SiO₂-induced aberrant expression of metabolites， including linoleic acid and glutamine （P<0.05， P<0.01）. Correlation analysis showed that Nrf2 and HO-1 were positively correlated with SOD and GSH-Px （P<0.05， P<0.01）， but negatively correlated with glutamine and serine （P<0.05， P<0.01）. ConclusionECT may activate the Nrf2/HO-1 pathway through its core active components， thereby regulating oxidative stress and metabolic disorders to ameliorate SiO₂-induced lung injury in rats. This study provides experimental evidence for ECT in the prevention and treatment of occupational lung injury.

Temporomandibular joint osteoarthritis is a common chronic degenerative disease,in which joint pain is the most signif-icant symptom,but its pathogenesis is still unclear.Significant subchondral bone lesions can occur in the early stage of osteoarthritis progression,and more and more experimental evidence shows that subchondral bone lesions play an important role in the pain caused by osteoarthritis.Osteoclasts,osteocytes,osteoblasts,endothelial cells,new generating nerves and blood vessels in the sub-chondral bone matrix microenvironment interact with each other and participate in the process of osteoarthritis pain.Therefore,regu-lating the subchondral bone matrix microenvironment is expected to become a new strategy to control joint pain.

Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.

Objective:To investigate the effects of miR-7-5p on the proliferation,apoptosis,and immune escape of esophageal squamous cell carcinoma(ESCC)KYSE-150 cells by regulating forkhead box M1(FOXM1).Methods:The targeted binding sites of miR-7-5p and FOXM1 were verified by the dual-luciferase reporter gene assay.The cancer tissues and adjacent paracancerous tissues as well as the basic clinical data of 56 ESCC patients hospitalized at Changzhou Geriatric Disease Hospital affiliated to Soochow University between January 2022 and October 2024 were collected.qRT-PCR was used to detect the expression levels of miR-7-5p and FOXM1 in ESCC tissues,and analyze the relationship between their expressions and clinicopathological characteristics.Normal cultured KYSE-150 cells were selected as the Control group Plasmids were transfected into KYSE-150 cells using Lipofectamine 3000 transfection reagent,and the cells were assigned into the Mimic-NC group,the miR-7-5p mimic group,the miR-7-5p mimic+OE-NC group,and the miR-7-5p mimic+OE-FOXM1 group.EdU staining and CCK-8 assay were used to detect the proliferation ability of KYSE-150 cells.Flow cytometry was performed to detect the apoptosis of KYSE-150 cells and CD8+T cells.Western blot assay was performed to detect the expression levels of PD-L1,FOXM1,BAX,and PCNA proteins in KYSE-150 cells.A nude mouse transplanted tumor model of KYSE-150 cells was established to observe the effects of miR-7-5p overexpression on the growth of the transplanted tumors and the expressions of Ki-67 and FOXM1 in the tissues.Results:miR-7-5p could target and negatively regulate FOXM1(P<0.05).miR-7-5p expression was low and FOXM1 expression was high in ESCC tissues(both P<0.05).The expressions of miR-7-5p and FOXM1 were significantly correlated with TNM stage and differentiation degree,respectively(all P<0.05).The rates of EdU-positive cells,cell proliferation ability,CD8+T cell apoptosis rate,as well as PD-L1,PCNA,and FOXM1 mRNA and protein in the miR-7-5p overexpression group were significantly reduced(all P<0.05),while the apoptosis rate,miR-7-5p,and BAX increased significantly(all P<0.05).Meanwhile,overexpression of FOXM1 could reverse the above effects(all P<0.05).Overexpression of miR-7-5p decreased the mass and volume of transplanted tumors,and the expressions of Ki-67 and FOXM1 proteins in transplanted tumor tissues(all P<0.05).Conclusion:Overexpression of miR-7-5p can significantly inhibit the proliferation and immune escape of KYSE-150 cells and promote cell apoptosis,which may be achieved by targeted negative regulation of FOXM1.

Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.

Temporomandibular joint osteoarthritis is a common chronic degenerative disease,in which joint pain is the most signif-icant symptom,but its pathogenesis is still unclear.Significant subchondral bone lesions can occur in the early stage of osteoarthritis progression,and more and more experimental evidence shows that subchondral bone lesions play an important role in the pain caused by osteoarthritis.Osteoclasts,osteocytes,osteoblasts,endothelial cells,new generating nerves and blood vessels in the sub-chondral bone matrix microenvironment interact with each other and participate in the process of osteoarthritis pain.Therefore,regu-lating the subchondral bone matrix microenvironment is expected to become a new strategy to control joint pain.

OBJECTIVE To explore the improving effect of luteolin （Lut） on placental dysfunction in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on hedgehog （Hh） signaling pathway. METHODS Twenty female rats were randomly selected as a control group and fed a normal diet. The remaining female rats were fed a high-fat and high-sugar diet for 8 weeks and then caged with male rats. Pregnant rats were administered 35 mg/kg streptozotocin intraperitoneally to establish GDM models. Successfully modeled female rats were randomly allocated to model group， SAG group （Hh signaling pathway activator SAG 50 mg/kg）， Lut low-dose group （Lut 40 mg/kg）， Lut high-dose group （Lut 80 mg/kg）， and Lut high+ITR group （Lut 80 mg/kg+Hh signaling pathway antagonist itraconazole 50 mg/kg）， with 20 rats in each group. Female rats in each drug group were intubated with the corresponding drug solution once a day for 19 days. After the final administration， the serum glucose- fat metabolic parameters （levels of fasting blood glucose and fasting insulin， insulin resistance index）， placental quality， placental permeability [Evan’s blue （EB） content]， and pathological changes in placental tissue were observed. The activities of superoxide dismutase （SOD）， the contents of malondialdehyde （MDA） and reduced glutathione （GSH）， and the protein expressions of Sonic Hh （Shh）， Patched-1 （Ptch1）， Smoothened （Smo） and Gli family zinc finger-1 （Gli1） in placental tissue were detected. HBB_ RESULTS Compared with the control group， rats in the model group showed narrow capillary lumens， perivascular fibrosis in placental tissue， and a significant increase in serum glucose-fat metabolic parameters， placental quality， contents of EB and MDA， while there was a significant decrease in SOD activity， GSH content， and protein expressions of Shh， Ptch1， Smo and Gli1 （P＜0.05）. Compared with the model group， rats in the SAG group， Lut low-dose and high-dose groups had widened capillary lumens， a significant decrease in perivascular fibrosis in placental tissue， serum glucose-fat metabolic parameters， placental qualities， EB and MDA contents， while there was a significant increase in SOD activities， GSH contents， and protein expressions of Shh， Ptch1， Smo and Gli1 （P＜0.05）， with the high-dose group showing no significant difference compared to the SAG group （P＞0.05）. The Hh signaling pathway antagonist itraconazole could significantly reverse the improving effects of Lut on the above indicators （P＜0.05）. CONCLUSIONS Lut can improve glucose metabolism parameters of GDM rats， reduce placental permeability， alleviate pathological damage to placental tissue， and reduce oxidative stress. These effects may be related to the activation of the Hh signaling pathway.

Objective To investigate the technique and dosage selection of indocyanine green(ICG)fluorescence staining in laparoscopic anatomical hemihepatectomy.Methods A retrospective cross-sectional study was conducted.The clinical date of the patients who underwent laparoscopic anatomical hemihepatectomy in the Cancer Hospital of the Chinese Academy of Medical Sciences from October 2020 to October 2023 was collected and analyzed,and the management of the Glissonean pedicle,the method and effect of ICG fluorescence staining during the operation,the dose of ICG injection,and the postoperative recovery were analyzed.Results A total of 91 laparoscopic anatomical hemihepatectomies were enrolled in this study,including 28 right hemihepatectomies and 63 left hemihepatectomies.The Glissonean pedicle was dissected intra-sheath in 9 cases and extra-sheath in 82 cases.ICG fluorescence staining was all performed using the negative staining method,of which 69 cases(75.8%)were successfully stained.The success rate of staining in the extra-sheath dissection and low-dose ICG group was higher than that in the intra-sheath dissection and high-dose ICG group.The average operation time was(168.5±32.2)minutes,the intraoperative bleeding volume was(152.4±56.3)ml,and the intraoperative blood transfusion rate was 6.6%(6/91),the average postoperative hospital stay was(8.5±2.6)days.One case was converted to laparotomy due to exophytic growth of the tumor compressing the Glissonean pedicle.Four cases had Clavien-Dindo Ⅰ-Ⅱ complications,all of which improved after treatment.There were 3 cases of grade Ⅲa complications,all of which were caused by bile leakage and abdominal cavity infection.They were cured by puncture and drainage.And there were no serious complications above grade Ⅲb.Conclusions In laparoscopic anatomical hemihepatectomy,the ICG fluorescence staining method was recommended to use the negative staining method of the extra-sheath dissection of the Glissonean pedicle,and a lower dose of ICG could help to increase the success rate of fluorescence staining.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*

Objective To evaluate the relationship between concurrent myocardial bridge at anterior descending branch and the formation of coronary atherosclerosis plaques by using transluminal attenuation gradient (TAG). Methods A total of 198 patients underwent coronary CTA in Renji Hospital of Shanghai Jiaotong University School of Medcine from June 2017 to March 2018 and the results showed the anterior descending myocardial bridge. The data were retrospectively analyzed. All patients completed the coronary CTA with 320?row detector CT. According to the manifestations of myocardial bridge on CTA,the patients were divided into deep and superficial myocardial bridge groups. According to whether the patients were complicated with coronary atherosclerotic plaques, they were divided into isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group. The thickness and length of myocardial bridge, the volume of coronary atherosclerotic plaques at the site of myocardial bridge, the pre?bridge and post?bridge TAG values, and the K ratio were recorded. Independent sample t test (normal distribution) or Mann?Whitney U test (skewed distribution) was used to compare the difference of measurement data among different groups. χ2 test was used to compare the difference of enumeration data among different groups. Pearson correlation test was used to analyze the correlation among pre?bridge and post?bridge TAG values,K ratio,thickness and length of myocardial bridge and plaque volume. The influence of above indexes on plaque occurrence was analyzed by binary logistic regression analysis. The relationship between main influence indexes and plaque formation was analyzed by receiver operating characteristic curve (ROC). Results Ninety nine patients had isolated myocardial bridge,99 with myocardial bridge and coronary atherosclerotic plaques,27 with superficial myocardial bridge and 171 with deep myocardial bridge. All atherosclerotic plaques occurred in pre?bridge and the mean volume of plaques was (91.6±83.0)mm3. The differences in sex, age, height, body weight and body mass index werenot statistically significant between isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group (all P>0.05). The difference in pre?bridge TAG value was statistically significant between the isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group (all P<0.05), but not statistically significant in post?bridge TAG value and K ratio (all P>0.05). The difference in pre?bridge and post?bridge TAG values and K value was not statistically significant between the superficial group and the deep group (all P>0.05). There was a weak negative correlation (r=-0.205,-0.316,-0.339,respectively,P<0.05) between the plaque volume and pre?bridge&post?bridge TAG values and K ratio. The pre?bridge TAG value significantly affected the plaque formation (P=0.014) and the odds ratio was 0.884 (95% CI 0.801 to 0.976). While other factors had no significant effects on plaque formation (all P>0.05). The area under curveof plaque formation promoted by pre?bridge TAG value was 0.582. When the diagnostic critical value was －37.26 HU/mm, the sensitivity and specificity of pre?bridge TAG value in plaque formation were 31.31% and 81.82%, respectively. Conclusion The TAG value of anterior descending bridge is an independent risk factor for plaque occurrence. The abnormal TAG value of anterior descending myocardial bridge can be detected early by CTA.