ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Objective: To analyze the relationship between cumulative ecological risks and physical activity behaviors of junior high school students, so as to provide theoretical support for promoting the physical and mental health development of junior high school students. Methods: From March to April 2023, a multistage random cluster sampling method was used to conduct an online survey of 3 502 middle school students in Henan Province. Physical activity levels and cumulative ecological risk were measured using the Physical Activity Rating Scale-3 and the Cumulative Ecological Risk Scale. Chisquare test and multiple Logistic regression were employed to examine the distribution and influencing factors of physical exercise behaviors among different student groups. Results: Slight physical exercise had the highest proportion of physical activity in tensity among junior high school students (48.5%), with 80.4% engaging in low levels of physical activity. Only 16.8% of students exercised ≥1 time daily, and the most common frequency was 1-2 times per week (44.1%). Gender, residential area, parental education, and peer support were all significantly associated with physical activity levels among junior high school students (χ2=122.53, 6.49, 7.49, 10.17, P<0.05). Logistic regression analysis showed that higher cumulative ecological risk scores were associated with a greater likelihood of engaging in low levels of physical activity compared to high levels (OR=1.12, 95%CI=1.02-1.23, P<0.05), but no significant association was found for moderate physical activity (OR=1.08, 95%CI=0.97-1.21, P>0.05). Conclusions Junior high school students in Henan Province generally engage in insufficient physical exercise. Cumulative ecological risk negatively predicts their physical activity behaviors.

Objective To investigate the therapeutic effects of interleukin 23p19(IL-23p19) monoclonal antibody in the MRL/lpr lupus-like mouse model. Methods A total of 36 female MRL/lpr mice aged 8 weeks were randomly divided into 6 groups: PBS group (blank control), IgG group (isotype IgG), dexamethasone (DEX) group (positive control), and three IL-23p19 monoclonal antibody treatment groups with different dose gradients: low dose (LD, 1 mg/kg), medium dose (MD, 3 mg/kg), and high dose (HD, 10 mg/kg). Drug intervention began at 12 weeks of age via tail vein injection. Urine protein levels were measured using urine protein test strips; serum anti-dsDNA antibody levels were detected by ELISA; serum creatinine and blood urea nitrogen levels were measured using an automatic biochemical analyzer; renal histopathological changes were analyzed by H&E and PAS staining; immunofluorescence was used to assess IgG and C3 immune complex deposition in kidney tissues; flow cytometry was employed to examine the expression of T helper 1(Th1), Th2, Th17, T follicular helper (Tfh), and regulatory T cells(Treg) cell subsets in the spleen; and RT-qPCR was used to detect the expression of related transcription factors in the spleen. Results IL-23p19 monoclonal antibody reduced urine protein levels, alleviated splenomegaly, improved renal function, and decreased anti-dsDNA antibody levels in MRL/lpr mice. It also mitigated glomerulonephritis and reduced renal immune complex deposition. Furthermore, IL-23p19 monoclonal antibody significantly suppressed the proportion of Th1 and Th17 cells while upregulating Treg cell proportion in the spleen. Additionally, it downregulated T-bet and retinoic acid receptor-related orphan receptor γt (RORγt) mRNA levels and upregulated forkhead box P3(FOXP3) mRNA levels in the spleen. Conclusions IL-23p19 monoclonal antibody demonstrates significant therapeutic effects in MRL/lpr mice, likely through modulation of the Th17/Treg cell balance.
Animals ; Female ; Mice, Inbred MRL lpr ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Antibodies, Monoclonal/therapeutic use* ; Interleukin-23 Subunit p19/immunology* ; Mice ; Lupus Nephritis/drug therapy* ; Kidney/drug effects* ; Antibodies, Antinuclear/blood*

OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Humans ; Human Umbilical Vein Endothelial Cells/drug effects* ; Cellular Senescence/drug effects* ; Autophagy/drug effects* ; Saponins/pharmacology* ; Ubiquitin-Protein Ligases/metabolism* ; Mitochondria/drug effects* ; Triterpenes/pharmacology* ; Protein Kinases/metabolism* ; Galactose/pharmacology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Membrane Potential, Mitochondrial ; Cell Proliferation/drug effects*

ObjectiveTo investigate the changes in cerebral blood perfusion in patients with acute cerebral infarction after taking Tongnaoyin， a traditional Chinese medicine， based on head and neck computed tomography （CT） angiography （CTA） combined with brain CT perfusion imaging （CTP）. MethodA total of 240 patients with cerebral infarction of phlegm and blood stasis syndrome treated in Jiangsu Province Hospital of Traditional Chinese Medicine from March 2018 to September 2023 were randomly divided into a control group （99 cases） and a Tongnaoyin group （141 cases）. Based on the guidelines， the control group was treated with conventional treatment such as anti-aggregation， anticoagulation， lipid-lowering and plaque stabilization， brain protection， and supportive treatment. The Tongnaoyin group was treated with Tongnaoyin of 200 mL in warm conditions in the morning and evening on the basis of the control group. Both groups underwent CTA combined with CTP within 24 hours after admission， and they were reexamined by CTA and CTP in the sixth month after admission. The degree of intracranial artery stenosis was determined according to the North American Symptomatic Carotid Endarterectomy Trial （NASCET） method. The relative cerebral blood volume （rCBV）， relative cerebral blood flow （rCBF）， mean transit time （MTT）， and time to peak （TTP） of the lesion area before and after treatment were compared. The adverse outcomes of the two groups within six months after discharge were compared. ResultCompared with the group before treatment， the degree of vascular stenosis in the Tongnaoyin group was significantly reduced， and the difference was statistically significant （Z=105.369，P<0.05）. Compared with the control group after treatment， the improvement rate of vascular stenosis in the Tongnaoyin group was higher （χ²=84.179，P<0.01）， and the curative effect was better.After treatment， the rCBV and rCBF of patients in the Tongnaoyin group were significantly increased， and the difference was statistically significant （P<0.01）. MTT and TTP showed a trend of shortening， but the difference was not statistically significant. There was no statistically significant difference in rCBV， rCBF， MTT， and TTP in the control group. Compared with those in the control group after treatment， the rCBV and rCBF in the Tongnaoyin group were significantly increased， while MTT and TTP were significantly reduced （P<0.01）. After six months of discharge， the risk of poor prognosis in the Tongnaoyin group was significantly reduced compared with the control group （P<0.05）. ConclusionTongnaoyin has a good effect on improving cerebral blood perfusion in patients with acute cerebral infarction. It can be used as an effective supplement for the conventional treatment of ischemic stroke to improve clinical efficacy.

Objective To discuss the value of clinical radiomic nomogram(CRN)and deep convolutional neural network(DCNN)in distinguishing atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 307 patients were retrospectively recruited from two institutions.Patients in institu-tion 1 were randomly divided into the training(n=184:APH=97,ALA=87)and internal validation sets(n=79:APH=41,ALA=38)in a ratio of 7∶3,and patients in institution 2 were assigned as the external validation set(n=44:APH=23,ALA=21).A CRN model and a DCNN model were established,respectively,and the performances of two models were compared by delong test and receiver operating characteristic(ROC)curves.A human-machine competition was conducted to evaluate the value of AI in the Lung-RADS classification.Results The areas under the curve(AUCs)of DCNN model were higher than those of CRN model in the training,internal and external validation sets(0.983 vs 0.968,0.973 vs 0.953,and 0.942 vs 0.932,respectively),however,the differences were not statistically significant(p=0.23,0.31 and 0.34,respectively).With a radiologist-AI com-petition experiment,AI tended to downgrade more Lung-RADS categories in APH and affirm more Lung-RADS cat-egories in ALA than radiologists.Conclusion Both DCNN and CRN have higher value in distinguishing APH from ALA,with the former performing better.AI is superior to radiologists in evaluating the Lung-RADS classification of pulmonary nodules.

Objective To explore the value of combined prediction model based on clinical and CT radiomics features in discriminating atypical pulmonary hamartoma(APH)from atypical lung adenocarcinoma(ALA).Methods A total of 290 patients with APH and ALA confirmed by pathology were retrospectively selected.250 patients from the First Affiliated Hospital of Anhui Medical University were randomly assigned into a training set(APH=91,ALA=84)and an internal validation set(APH=39,ALA=36)at a ratio of 7∶3,and other 40 patients from the First Affiliated Hospital of USTC were assigned as an external validation set(APH=21,ALA=19).The independent model and multivariate logistic regression combined model were constructed using the selected clinical-CT features and radiomics features,respectively,and a nomogram was drawn.Receiver operating characteristic(ROC)curve and DeLong test were used to evaluate and compare the performances of the models.Results The area under the curve(AUC)of the combined model established by 3 clinical-CT features and 4 radiomics features in the training set was 0.980,which was higher than that of clinical-CT model(AUC=0.885,P＜0.001)and radiomics model(AUC=0.975,P=0.042).The AUC of the combined model in the internal and external validation sets(0.963 vs 0.917)were also higher than those of clinical-CT model(0.858 vs 0.774)and radiomics model(0.953 vs 0.897),respectively.Conclusion The combined prediction model based on clinical and CT radiomics features can improve the differential diagnosis ability of APH and ALA.

Aim To explore the mechanism of oxiracetam promoting neurogenesis and migration in rats with cer-ebral infarction through stromal cell-derived factor-1α(SDF-1α)/C-X-C chemokine receptor 4(CXCR4)pathway.Methods 100 SD rats were randomly divided into control group,cerebral ischemia(CI)group,oxiracetam(200 mg/kg)group,and oxiracetam(200 mg/kg)+AMD3100(5 mg/kg)group,with 25 rats in each group.Electrocoagulation was used to create rat model of local permanent cerebral infarction.After 1,7 and 14 days of modeling,neurological deficits were scored,TTC staining was used to detect the volume of cerebral infarction,Nissl staining was used to detect cell surviv-al in the infarcted area,Western blot was used to detect SDF-1α and CXCR4 protein levels in ischemic zone.After 1～7 days of modeling,BrdU(50 mg/kg)was continuously injected intraperitoneally.After 14 days,immunofluorescence double staining was used to detect the number of BrdU+Nestin+and BrdU+DCX+cells in the SVZ region.5 days before modeling,retroviruses carrying GFP were injected into the SVZ region.After 14 days,immunofluorescence double stai-ning was used to detect the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in infarction area.C17.2 cells were divided into control group,oxygen-glucose deprivation(OGD)group,oxiracetam(final concentration:200 mg/L)group,and oxiracetam(final concentration:200 mg/L)+AMD3100(final concentration:100 μmol/L)group.OGD was used to create cell CI model.After 12 hours,immunofluorescence double staining was used to detect the number of Br-dU+/Nestin+and BrdU+/MAP-2+cells,Transwell experiment was used to detect cell migration,Western blot was used to detect SDF-1α and CXCR4 protein levels in cell culture supernatant.Results Animal experiment results showed:compared with control group,mNSS score in CI group was increased,cerebral infarction volume was increased,the number of surviving cells in infarcted area was decreased,SDF-1α and CXCR4 protein levels were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in SVZ region were increased(P＜0.05);compared with CI group,mNSS score in oxiracetam group was decreased,cerebral infarction volume was decreased,the number of surviving cells in infarc-ted area was increased,SDF-1α and CXCR4 protein levels were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in SVZ region were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in in-farcted area were increased(P＜0.05);compared with oxiracetam group,mNSS score in oxiracetam+AMD3100 group was increased,cerebral infarction volume was increased,the number of surviving cells in infarcted area was decreased,CXCR4 protein level was decreased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in the SVZ region were de-creased(P＜0.05).Cell experiment results showed:compared with control group,the number of BrdU+/Nestin+and Br-dU+/MAP-2+cells in OGD group were increased,the number of cell migration,SDF-1α and CXCR4 protein levels in cell culture supernatant were increased(P＜0.05);compared with OGD group,the number of BrdU+/Nestin+and BrdU+/MAP-2+cells in oxiracetam group were increased,the number of cell migration,SDF-1α and CXCR4 protein levels in cell culture supernatant were increased(P＜0.05);compared with oxiracetam group,the number of BrdU+/Nestin+and BrdU+/MAP-2+cells in oxiracetam+AMD3100 group were decreased,the number of cell migration,CXCR4 protein level in cell culture supernatant were decreased(P＜0.05).Conclusion Oxiracetam may promote the migration of neural stem cells from the SVZ region to the ischemic zone,promoting neurogenesis and functional recovery in rats with cerebral infarction by activating SDF-1α/CXCR4 pathway.

Objective To observe the value of 18F-FDG PET/CT semi-quantitative parameters for predicting spread through air spaces(STAS)of clinical stage Ⅰa—Ⅲa lung adenocarcinoma.Methods Data of 85 patients with clinical stage Ⅰa—Ⅲ a lung adenocarcinoma who underwent preoperative 18F-FDG PET/CT were retrospectively analyzed.The patients were divided into positive group(n=23)or negative group(n=62)according to whether pathology showed STAS or not.Clinical and PET/CT data were compared between groups,and logistic analysis was performed to explore the efficacy of each parameter for predicting STAS.Results Significant differences of gender,carcinoma embryonic antigen,clinical stage,pathological grade,micropapillary growth and proportion were found between groups(all P＜0.05).The maximum,the mean,the peak standard uptake value(SUVmax,SUVmean,SUVpeak),as well as the maximum,the mean and the peak standard uptake value normalized by lean body mass(SULmax,SULmean,SULpeak),also the total lesion glycolysis(TLG)in positive group were all significantly higher than those in negative group(all P＜0.05).Patients'gender,proportion of micropapillary growth,SUVmax and SULmax were all independent risk factors of STAS of clinical stage Ⅰa—Ⅲa lung adenocarcinoma.The area under the curve(AUC)of the above parameters for predicting STAS was 0.666,0.912,0.839 and 0.842,respectively,and of the combination was 0.957.Conclusion 18 F-FDG PET/CT semi-quantitative parameters SUVmax and SULmax were helpful for predicting STAS of clinical stage Ⅰa—Ⅲ a lung adenocarcinoma,and further combination of gender and proportion of micropapillary growth could improve diagnostic efficacy.

Objective:To investigate the risk factors of lower extremity deep venous thrombosis (LEDVT) in patients with sepsis during hospitalization in intensive care unit (ICU), and to construct a nomogram prediction model of LEDVT in sepsis patients in the ICU based on the critical care scores combined with inflammatory markers, and to validate its effectiveness in early prediction.Methods:726 sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from January 2015 to December 2021 were retrospectively included as the training set to construct the prediction model. In addition, 213 sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from January 2022 to June 2023 were retrospectively included as the validation set to verify the performance of the prediction model. Clinical data of patients were collected, such as demographic information, vital signs at the time of admission to the ICU, underlying diseases, past history, various types of scores within 24 hours of admission to the ICU, the first laboratory indexes of admission to the ICU, lower extremity venous ultrasound results, treatment, and prognostic indexes. Lasso regression analysis was used to screen the influencing factors for the occurrence of LEDVT in sepsis patients, and the results of Logistic regression analysis were synthesized to construct a nomogram model. The nomogram model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve, clinical impact curve (CIC) and decision curve analysis (DCA).Results:The incidence of LEDVT after ICU admission was 21.5% (156/726) in the training set of sepsis patients and 21.6% (46/213) in the validation set of sepsis patients. The baseline data of patients in both training and validation sets were comparable. Lasso regression analysis showed that seven independent variables were screened from 67 parameters to be associated with the occurrence of LEDVT in patients with sepsis. Logistic regression analysis showed that the age [odds ratio ( OR) = 1.03, 95% confidence interval (95% CI) was 1.01 to 1.04, P < 0.001], body mass index (BMI: OR = 1.05, 95% CI was 1.01 to 1.09, P = 0.009), venous thromboembolism (VTE) score ( OR = 1.20, 95% CI was 1.11 to 1.29, P < 0.001), activated partial thromboplastin time (APTT: OR = 0.98, 95% CI was 0.97 to 0.99, P = 0.009), D-dimer ( OR = 1.03, 95% CI was 1.01 to 1.04, P < 0.001), skin or soft-tissue infection ( OR = 2.53, 95% CI was 1.29 to 4.98, P = 0.007), and femoral venous cannulation ( OR = 3.72, 95% CI was 2.50 to 5.54, P < 0.001) were the independent influences on the occurrence of LEDVT in patients with sepsis. The nomogram model was constructed by combining the above variables, and the ROC curve analysis showed that the area under the curve (AUC) of the nomogram model for predicting the occurrence of LEDVT in patients with sepsis was 0.793 (95% CI was 0.746 to 0.841), and the AUC in the validation set was 0.844 (95% CI was 0.786 to 0.901). The calibration curve showed that its predicted probability was in good agreement with the actual probabilities were in good agreement, and both CIC and DCA curves suggested a favorable net clinical benefit. Conclusion:The nomogram model based on the critical illness scores combined with inflammatory markers can be used for early prediction of LEDVT in ICU sepsis patients, which helps clinicians to identify the risk factors for LEDVT in sepsis patients earlier, so as to achieve early treatment.