ObjectiveTo investigate the association of the traditional Chinese medicine （TCM） syndrome types of primary liver cancer （PLC） with clinical features and multimodal quantitative radiological features on computed tomography （CT） and magnetic resonance imaging （MRI）， and to provide a reference for the objectification of TCM syndrome differentiation and precise diagnosis and treatment. MethodsA retrospective analysis was performed for the clinical data of 312 patients who were diagnosed with PLC in The First Affiliated Hospital of Hunan University of Chinese Medicine from March 2020 to June 2025， and according to the TCM syndrome type， they were divided into stagnation of liver Qi group with 40 patients， stagnation of liver Qi and spleen deficiency group with 109 patients， Qi stagnation and blood stasis group with 62 patients， dampness-heat toxin amassment group with 81 patients， and liver-kidney Yin deficiency group with 20 patients. Clinical features and multimodal quantitative radiological features were compared between the patients with different TCM syndrome types. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s multiple test was used for further comparison between two groups； the chi-square test was used for comparison of categorical data between groups， and the Bonferroni method was used for further comparison between two groups. ResultsThere were significant differences between the patients with different TCM syndrome types in China liver cancer staging （CNLC）， Child-Pugh class， alanine aminotransferase， aspartate aminotransferase， albumin， direct bilirubin， total bilirubin， prothrombin time， neutrophil， and albumin-bilirubin score （all P<0.05）. In the stagnation of liver Qi group， the patients with Child-Pugh class A accounted for 75.00%； among the patients with CNLC stage I PLC， the patients with stagnation of liver Qi accounted for 60.00%， and those with Qi stagnation and blood stasis syndrome accounted for 59.68%， while among the patients with CNLC stage IV PLC， the distribution proportion of dampness-heat toxin amassment （27.16%） and liver-kidney Yin deficiency （30.00%） was significantly higher than that of stagnation of liver Qi （2.50%） （all P<0.05）. Radiological examination showed that there were significant differences between the patients with different TCM syndrome types in the number of tumors， ascites， venous tumor thrombus， maximum tumor diameter， intrahepatic metastasis， and lymph node metastasis in the hepatic hilar and retroperitoneal regions （all P<0.05）. Compared with the patients with stagnation of liver Qi， the patients with liver depression and spleen deficiency or liver-kidney Yin deficiency were more likely to develop intrahepatic metastasis； the patients with liver depression and spleen deficiency， dampness-heat toxin amassment， or liver-kidney Yin deficiency were more likely to develop lymph node metastasis in the hepatic hilar and retroperitoneal regions； the patients with liver-kidney Yin deficiency were more likely to experience multiple tumors； the patients with liver depression and spleen deficiency or dampness-heat toxin amassment were more likely to develop ascites （all P<0.05）. Compared with the patients with Qi stagnation and blood stasis syndrome， the patients with liver depression and spleen deficiency had a significantly longer maximum tumor diameter and a significantly higher proportion of patients with venous tumor thrombus （both P<0.05）. Furthermore， among the 184 patients with MRI diffusion-weighted imaging sequences， the patients with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome had significantly higher ADC values and relative ADC values than those with stagnation of liver Qi （all P<0.05）. ConclusionThere are significant differences in CT/MRI radiological features and clinical features between PLC patients with different TCM syndrome types， among whom the patients with liver depression and spleen deficiency， dampness-heat toxin amassment， and liver-kidney Yin deficiency tend to exhibit progressive radiological features， and those with dampness-heat toxin amassment or Qi stagnation and blood stasis syndrome tend to have higher ADC values. These findings provide an objective basis for TCM syndrome differentiation in PLC.

OBJECTIVES: To investigate the effects of Naoluo Xintong Decoction (NLXTD) on proliferation of rat brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reoxygenation (OGD/R) injury and role of the HIF-1α/VEGF pathway in mediating its effect. METHODS: Using a BMEC model of OGD/R, we tested the effects of 10% NLXTD-medicated rat serum, alone or in combination with 2ME2 or 10% NAKL, on cell proliferation, migration, tube-forming ability and permeability using CCK-8 assay, Transwell chamber assay, tube formation assay and permeability assay. Cellular expressions of VEGF and Notch were detected using ELISA and laser confocal immunofluorescence analysis, and the expressions of HIF-1α, VEGFR2, Notch1, ERK and P-ERK1/2 proteins were detected with Western blotting. RESULTS: OGD/R injury significantly decreased viability of BMECs. NLXTD treatment of the cells with OGD/R could significantly promoted cell proliferation, migration and tube formation ability, but these effects were strongly attenuated by application of 2ME2. NLXTD treatment also significantly increased the percentages of VEGF- and Notch-positive cells in the cell models and obviously enhanced the expression levels of HIF-1α, VEGFR2, Notch1 and P-ERK1/2. CONCLUSIONS NLXTD promotes proliferation, migration, and tube formation of rat BMECs after OGD/R injury possibly by activating the HIF-1α/VEGF signaling pathway.
Animals ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Rats ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Glucose ; Brain/blood supply* ; Cells, Cultured ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor Receptor-2/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia

BACKGROUND: Previous evidence showed that ambient air pollution and cardiovascular mortality are related. However, there is a lack of evidence towards the modification effect of long-term lifestyle on the association between short-term ambient air pollution and death from cardiovascular events. METHOD: A total of 14,609 death from major adverse cardiovascular events (MACE) were identified among the China Kadoorie Biobank participants from 2013 to 2018. Ambient air pollution exposure including particulate matter 2.5 (PM_2.5), SO₂, NO₂, CO, and O₃ from the same period were obtained from space-time model reconstructions based on remote sensing data. Case-crossover design and conditional logistic regression was applied to estimate the effect of short-term exposure to air pollutants on MACE mortality. RESULTS: We found MACE mortality was significantly associated with PM_2.5 (relative percent increase 2.91% per 10 µg/m³ increase, 95% CI 1.32-4.53), NO₂ (5.37% per 10 µg/m³ increase, 95% CI 1.56-9.33), SO₂ (6.82% per 10 µg/m³ increase, 95% CI 2.99-10.80), and CO (2.24% per 0.1 mg/m³ increase, 95% CI 1.02-3.48). Stratified analyses indicated that drinking was associated with elevated risk of MACE mortality with NO₂ and SO₂ exposure; physical inactivity was associated with higher risk of death from MACE when exposed to PM_2.5; and people who had balanced diet had lower risk of MACE mortality when exposed to CO and NO₂. CONCLUSIONS The study results showed that short-term exposure to ambient PM_2.5, NO₂, SO₂, and CO would aggravate the risk of cardiovascular mortality, yet healthy lifestyle conduct might mitigate such negative impact to some extent.
Humans ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Middle Aged ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Exposure/adverse effects* ; Life Style ; Aged ; Adult ; Risk Factors ; Cross-Over Studies ; East Asian People

Objective To investigate the effects of Naoluo Xintong Decoction(NLXTD)on proliferation of rat brain microvascular endothelial cells(BMECs)after oxygen-glucose deprivation/reoxygenation(OGD/R)injury and role of the HIF-1α/VEGF pathway in mediating its effect.Methods Using a BMEC model of OGD/R,we tested the effects of 10%NLXTD-medicated rat serum,alone or in combination with 2ME2 or 10%NAKL,on cell proliferation,migration,tube-forming ability and permeability using CCK-8 assay,Transwell chamber assay,tube formation assay and permeability assay.Cellular expressions of VEGF and Notch were detected using ELISA and laser confocal immunofluorescence analysis,and the expressions of HIF-1α,VEGFR2,Notch1,ERK and P-ERK1/2 proteins were detected with Western blotting.Results OGD/R injury significantly decreased viability of BMECs.NLXTD treatment of the cells with OGD/R could significantly promoted cell proliferation,migration and tube formation ability,but these effects were strongly attenuated by application of 2ME2.NLXTD treatment also significantly increased the percentages of VEGF-and Notch-positive cells in the cell models and obviously enhanced the expression levels of HIF-1α,VEGFR2,Notch1 and P-ERK1/2.Conclusion NLXTD promotes proliferation,migration,and tube formation of rat BMECs after OGD/R injury possibly by activating the HIF-1α/VEGF signaling pathway.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

Objective To explore the efficacy of vacuum-assisted minimally invasive gyrotomy for benign lesions in the lower quadrant of the breast.Methods From August 2022 to August 2023,90 patients with benign lesions in the lower quadrant of the breast were treated.According to the different surgical methods,they were divided into two groups:the traditional group included 45 cases,which underwent surgery through the trans-areolar incision;the minimally invasive group included 45 cases,which underwent surgery through the trans-mammary fold incision with vacuum-assisted minimally invasive technique.The surgical-related indicators,inflammatory response indicators,patient satisfaction,and safety were compared between the two groups.Results The operation time[(20.45±6.18)min],intraoperative bleeding[(7.78±2.23)ml],hospital stay[(4.37±1.05)d],scar length[(2.32±0.42)cm]and healing time[(3.46±1.08)d]in the minimally invasive group were significantly better than those in the traditional group[(34.52±9.46)min,(23.16±6.44)ml,(8.72±2.73)d,(19.14±4.18)cm and(7.37±2.16)d](P＜0.05).The levels of IL-6[(12.14±2.86)ng/L],IL-10[(14.33±3.74)pg/ml],CRP[(13.85±3.11)mg/L],Cor[(131.27±6.43)nmol/L]and NE[(82.55±8.44)in the minimally invasive group at 3 days after surgery ng/ml were increased and VEGF was decreased[(59.72±7.44)mg/L]than the traditional group[(17.23±3.38)ng/L,(19.62±4.88)pg/ml,(28.36±4.67)mg/L,(196.52±8.84)nmol/L,(117.62±7.14)ng/ml and(88.46±7.89)mg/L](P＜0.05).The satisfaction of patients in minimally invasive group(97.78％,44/45)was significantly higher than that in traditional group(82.22％,37/45)(P＜0.05).The incidence of adverse events in minimally invasive group(4.44％,2/45)was significantly lower than that in traditional group(22.22％,10/45)(P＜0.05).Conclusion Vacuum-assisted minimally invasive rotatory excision can optimize surgical indicators,improve serological indicators,enhance patient satisfaction and treatment safety compared to traditional areola incision surgery.

Objective To explore the efficacy of vacuum-assisted minimally invasive gyrotomy for benign lesions in the lower quadrant of the breast.Methods From August 2022 to August 2023,90 patients with benign lesions in the lower quadrant of the breast were treated.According to the different surgical methods,they were divided into two groups:the traditional group included 45 cases,which underwent surgery through the trans-areolar incision;the minimally invasive group included 45 cases,which underwent surgery through the trans-mammary fold incision with vacuum-assisted minimally invasive technique.The surgical-related indicators,inflammatory response indicators,patient satisfaction,and safety were compared between the two groups.Results The operation time[(20.45±6.18)min],intraoperative bleeding[(7.78±2.23)ml],hospital stay[(4.37±1.05)d],scar length[(2.32±0.42)cm]and healing time[(3.46±1.08)d]in the minimally invasive group were significantly better than those in the traditional group[(34.52±9.46)min,(23.16±6.44)ml,(8.72±2.73)d,(19.14±4.18)cm and(7.37±2.16)d](P＜0.05).The levels of IL-6[(12.14±2.86)ng/L],IL-10[(14.33±3.74)pg/ml],CRP[(13.85±3.11)mg/L],Cor[(131.27±6.43)nmol/L]and NE[(82.55±8.44)in the minimally invasive group at 3 days after surgery ng/ml were increased and VEGF was decreased[(59.72±7.44)mg/L]than the traditional group[(17.23±3.38)ng/L,(19.62±4.88)pg/ml,(28.36±4.67)mg/L,(196.52±8.84)nmol/L,(117.62±7.14)ng/ml and(88.46±7.89)mg/L](P＜0.05).The satisfaction of patients in minimally invasive group(97.78％,44/45)was significantly higher than that in traditional group(82.22％,37/45)(P＜0.05).The incidence of adverse events in minimally invasive group(4.44％,2/45)was significantly lower than that in traditional group(22.22％,10/45)(P＜0.05).Conclusion Vacuum-assisted minimally invasive rotatory excision can optimize surgical indicators,improve serological indicators,enhance patient satisfaction and treatment safety compared to traditional areola incision surgery.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Objective:To investigate the carriage status of Neisseria meningitidis ( Nm) among the healthy population in Hebei Province for the prevention and control of meningitis. Methods:From 2015 to 2022, throat swabs were collected from health people, which were selected by cluster random sampling in 11 cities of Hebei.The positive rate of Nm was detected by bacterial culture. The serogroups of isolated strains were identified.The laboratory detection results of Nm strains, combined with epidemiological survey data, were synthetically analyzed. Results:A total of 20 245 people were investigated; 249 strains of Nm were isolated; the overall Nm carriage rate was 1.23%. The carriage rate was significantly higher in men than in women(χ 2=28.831, P<0.05). The positive rates of Nm in different age groups were significantly different(χ 2=428.018, P<0.05), with the highest rates in the 15-19 year-old group(4.90%, 149/3 042). The positive rates of Nm were significantly different in different regions(χ 2=177.512, P<0.05), with the highest positive rate of Nm in Xingtai, Shijiazhuang, Chengde and Baoding city in sequence. Among the isolated Nm strains, ungroupable serogroups, serogroup B, serogroup C, and serogroup W accounted for 71.49%(178/249), 13.65%(34/249), 6.83%(17/249) and 4.42%(11/249), respectively. Conclusions:The carriage rate of Nm among healthy population is generally low in Hebei Province. It is recommended to continue to strengthen monitoring, pay attention to the changes and distribution characteristics of Nm, and formulate scientific and targeted prevention and control measures of meningococcal disease.