Lung cancer （LC） is a significant global public health issue， with both its incidence and mortality rates ranking among the highest worldwide. The age-standardized incidence and mortality rates are increasing annually， posing a serious threat to the life and health of LC patients. Radical surgical resection is the primary treatment for malignant lung tumors. However， postoperative multidimensional functional impairments， including respiratory， mucosal， and psychological functions， are common. These impairments not only reduce patients' quality of life and affect their treatment tolerance and duration， but also negatively correlate with prognosis， facilitating disease recurrence and metastasis. At present， postoperative functional dysfunction after LC surgery remains a key clinical challenge that urgently needs to be addressed. There is a lack of standardized and regulated postoperative rehabilitation treatment management and traditional Chinese medicine （TCM） differentiation and treatment strategies for LC. Focusing on the core underlying pathogenesis of "Qi sinking" after LC surgery， and guided by the classical TCM theory of "lungs governing Qi"， this study， based on the core concept of the "five perspectives on treatment" theory， innovatively proposes the respiratory dysfunction as the core pathogenesis of "Qi sinking in the chest" during the rapid rehabilitation phase， mucosal dysfunction as the core pathogenesis of "Yin deficiency and Qi sinking" during the postoperative adjuvant treatment phase， and the psychological dysfunction as the core pathogenesis of "Qi sinking with emotional constraint" during the consolidation phase. Accordingly， stage-specific dynamic functional protection strategies are constructed. In the rapid rehabilitation phase， the strategy emphasizes tonifying Qi and uplifting sinking Qi， with differentiation and treatment based on the principle of ''descending before ascending''. In the adjuvant treatment phase， the approach focuses on nourishing Yin and uplifting Qi， with prescription combinations that integrate unblocking and tonification. In the consolidation phase， the strategy aims to resolve constraint and uplift Qi， with clinical treatment emphasizing a combination of dynamic and static methods. At each stage of functional rehabilitation， clinical differentiation and treatment should support healthy Qi and eliminate pathogenic factors simultaneously. This study is the first to propose the concept of postoperative functional protection in TCM， offering a new approach for TCM differentiation and treatment in the full-cycle， stage-based， and dynamic protection of postoperative function in LC patients. It is expected to contribute to the construction and development of an integrated TCM-Western medicine comprehensive program for cancer prevention and treatment in China.

ObjectiveTo investigate the relationship between the non-fasting triglyceride and glucose （TyG） index and hyperglycemia in pregnancy during the third trimester in high altitudes. MethodsThis study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region， from January 2023 to April 2025. The non-fasting TyG index was calculated from non-fasting triglyceride （TG） and random plasma glucose （PG）. Based on the tertiles of the non-fasting TyG index values， the individuals were split into three groups （corresponding to non-fasting TyG index of 8.89 and 9.21， respectively）. The baseline clinical characteristics， lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups. Statistical analyses were performed using ANOVA， Kruskal-Wallis H test， Chi-square test， or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting. ResultsA total of 774 Tibetan singleton pregnant women were included， with a average age of 27.3 ± 6.1 years， a pre-delivery body mass index （Pre-BMI） of （25.2±2.3）kg/m² ， a proportion of 26.7% （207/774） primigravid women， the mean non-fasting TyG index was 9.1 ± 0.4。Thirty pregnant women were diagnosed with hyperglycemia in pregnancy， with a detection rate of 3.9% （30/774）. Statistically significant differences in serum total cholesterol （TC）， TG， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） levels were identified when comparing different non-fasting TyG groups （all P values <0.05）. Subsequent trend test analysis indicated that the levels of TC， TG， LDL-C， and PG gradually increased with elevated the non-fasting TyG index （ F_{trend TC}=95.61， P<0.001； F_{trend TG}=1 051.91， P<0.001； F_{trend LDL-C} = 97.20， P < 0.001； F_{trend TG}=195.20； P<0.001）. After adjustment for maternal age， pre-delivery BMI， altitude， TC， LDL-C， and HDL-C， multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy （Model 1： OR=2.72， 95% CI： 1.13-6.53， P=0.026； Model 2： OR=2.56， 95% CI： 1.01-6.50， P=0.048； Model 3： OR=2.72， 95% CI： 1.06-6.97， P=0.037； Model 4： OR=4.02， 95% CI： 1.42-11.40， P=0.009） and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index， however， this association did not statistical significance （P _trend >0.05）. Curve fitting by restricted cubic splines （RCS） were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy， and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy （P _{for non-linear} = 0.515）. ConclusionNon-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.

OBJECTIVES: To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress. METHODS: Twenty male SD rats were randomized equally into control group and heat stress group. After exposure to 32 ℃ for 2 weeks in the latter group, the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry. In the cell experiments, cultured rat thoracic aortic endothelial cells (RTAECs) were incubated at 40 ℃ for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA (si-Bmal1) or a negative sequence. In both rat thoracic aorta and RTAECs, the expressions of Bmal1, the cell cycle proteins CDK1, CDK4, CDK6, and cyclin B1, and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting. TUNEL staining was used to detect cell apoptosis in rat thoracic aorta, and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry. RESULTS: Compared with the control rats, the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1, cyclin B1 and CDK1 in the thoracic aorta (P<0.05). In cultured RTAECs, heat stress caused significant increase of Bmal1, cyclin B1 and CDK1 protein expression levels, which were obviously lowered in cells with prior si-Bmal1 transfection. Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2. CONCLUSIONS Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells, which can be partly alleviated by suppressing Bmal1 expression.
Animals ; ARNTL Transcription Factors/genetics* ; Male ; Aorta, Thoracic/metabolism* ; Rats ; Rats, Sprague-Dawley ; Endothelial Cells/metabolism* ; Apoptosis ; Cells, Cultured ; Heat-Shock Response ; Cyclin B1/metabolism* ; CDC2 Protein Kinase/metabolism* ; Cyclins/metabolism* ; RNA, Small Interfering ; bcl-2-Associated X Protein/metabolism*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective:To discuss the effect of prostaglandin E2(PGE2),a pyrogenic mediator,on the discharge activity of warm-sensitive neurons(WSNs)in median preoptic nucleus(MnPO)of hypothalamus in the female mice,and to clarify its mechanism.Methods:Coronal brain slices of MnPO were prepared from the female mice.The slices were then perfused with artificial cerebrospinal fluid(ACSF)containing synaptic transmission blockers(STBs).The discharge frequency was monitored using the patch clamp technique while changing the temperature of the perfusate to identify the WSNs.A total of 32 MnPO WSNs were divided into base line group(n=32)and PEG2(n=32).The patch clamp technique was employed to monitor the discharge frequencies of MnPO WSNs following the perfusion of ACSF and 1 μmol·L-1 PGE2,respectively.The MnPO WSNs with good activity and significant change in discharge frequency after PGE2 perfusion were divided into PGE2 receptor E-series prostaglandin receptrol(EP)1 antagonist(EP1 ant)+PGE2 group(n=7),EP3 ant+PGE2 group(n=7),and EP4 ant+PGE2 group(n=7).The patch clamp technique was used to monitor the discharge frequencies of MnPO WSNs following the perfusion of 3 μmol·L-1 EP1 ant and 1 μmol·L-1 PGE2 mixture,10 μmol·L-1 EP3 ant and 1 μmol·L-1 PGE2mixture,and 10 μmol·L-1 EP4 ant and 1 μmol·L-1 PGE2 mixture,respectively.Resluts:After perfuson of the ACSF containing STBs,a total of 188 MnPO neurons from the female mice with an intrinsic temperature sensitivity coefficient(m value)were identified;out of these,32 neurons had an m value of ≥0.8 and were identified as MnPO WSNs,accounting for approximately 17％of all recorded neurons.Compared with baseline discharge frequency,the discharge frequency of MnPO WSNs after addition of PGE2 was decreased(P＜0.05).Compared with PGE2 group,the percentage change in discharge frequency of MnPO WSNs in EP3 ant+PGE2 group was significantly decreased(P＜0.05).Compared with PGE2 group,the percentage change in discharge frequency of MnPO WSNs in EP1 ant+PGE2 group had no significant difference(P＞0.05).Compared with PGE2 group,the percentage change in discharge frequency of MnPO WSNs in EP4 ant+PGE2 group had no significant difference(P＞0.05).Conclusion:In the female mice,WSNs make up approximately 17％of the total neurons in MnPO.PGE2 can directly inhibit the discharge activity of MnPO WSNs in the female mice through postsynaptic mechanism involving EP3 receptors.

ObjectiveTo establish a method using ultra-high performance liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） for the detection of six common trichothecene toxins in oats. MethodsOats were selected as the research subject in this study. Response surface design was used to optimize the QuEChERS extraction method. Additionally， a rapid and efficient strategy for sample extraction and purification was developed. Combined with UHPLC-MS/MS， six commonly co-occurring trichothecene toxins in oats were quantitatively analyzed simultaneously. ResultsThis method demonstrated good analytical performance for each analyte across the corresponding concentration ranges （r>0.99）， with accuracy ranging from 87.26% to 99.64%. The inter-day and intra-day relative standard deviations were less than 6.8% and 5.5%， respectively， indicating its potential for practical application. This method was used to detect mycotoxins in 12 oat samples from China， and it was found that one sample exceeded the standard limits for deoxynivalenol （DON）， and the co-contamination of trichothecene toxin was prevalent. ConclusionThe risk posed by these toxins has been underestimated. Ongoing， extensive monitoring is necessary to provide contamination data to assess the consumer risk.

AIM: To observe the early retinal degeneration and activation of microglia in C57BL/6N(Crb1rd8/rd8)mice.METHODS:Totally 15 male SPF C57BL/6N mice and 15 male SPF C57BL/6J mice were raised normally, and fundus photography examinations were performed by Micron-Ⅲ at the time of 0, 4, 8, 12 wk of enrollment to calculate the number and area of retinopathy. At the end of experiment, all mice were sacrificed and the right eyeballs were removed to prepare retinal tissue slices. After HE staining, the retinal tissue morphology was observed under optical microscope while the location and level of CX3CR1 expression were detected in immunohistochemical staining. The left eyeballs were removed to isolate retina, then Western-Blot was used to analyze the expression of CD86 and CD206 proteins in retina, and the concentration of IL-1β, IL-6, TNF-α, IL-4 and IL-10 in retina was detected by electrochemiluminescence.RESULTS:The result of fundus photography examinations showed that the number of retinopathy in the C57BL/6N significantly increased at 4, 8, and 12 wk, and there were differences in variations compared with the C57BL/6J at the same time point(all P<0.05). In the changes in area of retinopathy, there was a difference between two groups at 12 wk(P<0.05), but no difference in variations within groups(both P>0.05). HE staining of retinal tissue showed that the retinal structure of C57BL/6N mice was abnormal, with loose and disordered cell arrangement, and the photoreceptor layer was obviously protruding to the inner side of retina with a drusen-like protrusion. The retinal structure of C57BL/6J mice was clearer, with orderly cell arrangement and no obvious abnormality. Immunohistochemical results showed that CX3CR1 was highly expressed in ganglion cell layer, inner and outer plexiform layer, photoreceptor cell layer and lesion in the retina of C57BL/6N mice, with a mean density of 0.285±0.056 in C57BL/6N and 0.189±0.084 in C57BL/6J mice(P<0.05). The results of Western-Blot showed that the expression of CD86 and CD206 in retina of C57BL/6N increased compared with that in C57BL/6J to varying degrees, and the difference of CD86 was statistically significant(P<0.05). The results of cytokine detection showed that the level of IL-1β, TNF-α in C57BL/6N was significantly higher than that of C57BL/6J, while IL-10 was significantly lower(all P<0.05).CONCLUSION: The retinal degeneration of C57BL/6N(Crb1rd8/rd8)mice progressed slowly and gradually aggravated with age. The retinal structure of the lesion was disordered and accompanied by microglial infiltration dominated by M1 polarization.

Objective:To compare the effects of different test meals on postprandial triglycerides and to optimize the standard meal composition and the blood sampling protocol for the oral fat tolerance test.Methods:This study is a prospective, open-label, randomized, cross-over trial. In March 2023, 36 volunteers were recruited in Hebei General Hospital. They underwent a health examination and oral glucose tolerance test. Twenty-six healthy volunteers(11 males and 15 females) were included in this study, with an average age of(39.08±4.56) years. Each volunteer received 75 g protein meal, 75 g fat meal, 700 kcal fixed-calorie high-fat mixed meal, and a high-fat mixed meal with energy adjusted based on 10 kcal/kg body weight. A one-week washout period of regular diet was applied before each trial. Blood was collected at fasting status and 1, 2, 3, 4, 5, and 6 hours after a meal to detect serum triglycerides, total cholesterol, low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), glucose, and insulin. The variations of postprandial metabolic indicators over time following the consumption of different test meals were analyzed. The disparities in postprandial metabolic responses between the two types of mixed meals were compared.Results:The protein meal, fat meal, fixed-calorie high-fat mixed meal, and adjusted-calorie high-fat mixed meal resulted in postprandial triglyceride increases of 22.45%, 115.40%, 77.14%, and 63.63%, and insulin increase of 560.43%, 85.69%, 554.18%, and 598.97%, respectively, and with reductions in total cholesterol, LDL-C, and HDL-C ranging from 5.64%-21.81%, respectively. The blood glucose changed slightly. Changes in metabolic indicators mainly occured within 4 hours. The comparison of the characteristics of postprandial triglycerides between the two high-fat mixed meals showed no statistically significant differences( P>0.05). Conclusion:A standardize protocol with a 700 kcal fixed-calorie high-fat mixed meal as test meal, and blood lipid levels measured at fasting and at 1, 2, 3, and 4 hours after consumption, can serve as an optimized approach for oral fat tolerance test.

AIM: To explore retinal microvascular changes in migraine patients using meta-analysis.METHODS: The National Library of Medicine PubMed, Embase, and Cochrane Library were searched to find relevant studies, and the search period was from the creation of database to June 2023. Two investigators independently screened the literatures, extracted data, and evaluated the quality of included studies using the NOS scale. STATA15.0 was used for Meta-analysis and publication bias evaluation, sensitivity analysis was performed for results with large heterogeneity, and the funnel plot and Egger were used to assess the publication bias of the literature.RESULTS:A total of 12 studies, including 217 patients(252 eyes)with migraine with aura(MA), 283 patients(388 eyes)with migraine without aura(MO), and 374 healthy individuals(479 eyes), were included in this Meta-analysis. Several optical coherence tomography angiography(OCTA)indicators, including foveal avascular zone(FAZ)macular or optic disc perfusion density were compared and analyzed. The Meta-analysis results showed that compared with healthy controls, patients with MA had a significant increase in FAZ area and perimeter, a significant decrease in perfusion density of the macular deep capillary plexus(mDCP)except for the fovea, and a significant decrease in perfusion density of the radial peripapillary capillaries(RPC)around the optic disc; the FAZ parameters were significantly increased in MO, while the differences in perfusion density of the macular superficial capillary plexus(mSCP), mDCP and RPC were not statistically significant, except for the perfusion density in the parafovea mDCP.CONCLUSIONS: Both MA and MO patients had an enlarged FAZ area, patients with MA had a significant decrease in mDCP perfusion density, and migraine patients had some degree of retinal ischemia.