ObjectiveTo investigate the effects of Yishen Juanbi pills （YSJB）-containing bone marrow fluid on the migration and differentiation phenotypes of CD4⁺T lymphocytes based on the stromal cell-derived factor-1/chemokine receptor 4 （SDF-1/CXCR4） signaling pathway. MethodsPrimary CD4⁺T lymphocytes were isolated from mice using magnetic bead separation and identified for purity by flow cytometry. A CD4⁺T lymphocyte culture system was then established to observe the effects of SDF-1 on CD4⁺T-cell migration and differentiation. On this basis， the experimental groups included the Sham group， the ovariectomy （OVX） group， the Sham+collagen-induced arthritis （CIA） group， the OVX+CIA group， the Sham+CIA+YSJB group （2.16 g·kg^-1）， the OVX+CIA+YSJB group （2.16 g·kg^-1）， and the OVX+CIA+methotrexate （MTX） group （1.5 mg·kg^-1）. Bone marrow fluid from each group was prepared according to previous methods and added to the CD4⁺ T-cell culture system at 5% （v/v）. Transwell assays were used to examine CD4⁺T-cell migration in each group. Real-time PCR was used to measure the mRNA expression levels of interleukin （IL）-17， tumor necrosis factor-α （TNF-α）， retinoic-acid-related orphan receptor γt （RORγt）， IL-10， transforming growth factor-β （TGF-β）， forkhead box P3 （FoxP3）， CXCR4， phosphoinositide 3-kinase （PI3K）， and protein kinase B （Akt）. Western blot was used to detect the expression of helper T （Th）17/regulatory T （Treg） cell signature factors （RORγt， FoxP3）， CXCR4， PI3K， phosphorylated （p）-PI3K， Akt， and p-Akt. In a separate set of experiments， cells were divided into the Sham group， OVX+CIA group， OVX+CIA+CXCR4 antagonist AMD3100 group， and OVX+CIA+YSJB+AMD3100 group to observe changes in the above indicators following AMD3100 intervention. ResultsCompared with the Sham group， the number of migrated cells in the lower chamber was significantly increased in the Sham+CIA and OVX+CIA groups （P<0.05， P<0.01）. The mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was significantly upregulated， whereas FoxP3， IL-10， and TGF-β mRNA expression was significantly decreased （P<0.05， P<0.01）. Protein expression of RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt was significantly increased， while FoxP3 protein expression was markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA group， the OVX+CIA+YSJB group and OVX+CIA+MTX group showed significantly reduced migration （P<0.05）， mRNA expression of RORγt， IL-17， TNF-α， CXCR4， PI3K， and Akt was also significantly decreased， while FoxP3， IL-10， and TGF-β mRNA expression was significantly increased （P<0.05， P<0.01）. RORγt protein expression was significantly downregulated， and FoxP3 protein expression markedly upregulated （P<0.05）. In the OVX+CIA+YSJB group， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was significantly decreased （P<0.05）. Compared with the OVX+CIA group， RORγt， CXCR4， PI3K， and Akt mRNA expression in CD4⁺T cells was significantly decreased in the OVX+CIA+AMD3100 group and the OVX+CIA+YSJB+AMD3100 group， while FoxP3 mRNA and protein expression was significantly upregulated （P<0.05， P<0.01）. RORγt， CXCR4， p-PI3K/PI3K， and p-Akt/Akt protein expression was also markedly decreased （P<0.05， P<0.01）. Compared with the OVX+CIA+AMD3100 group， the OVX+CIA+YSJB+AMD3100 group showed significantly decreased RORγt and Akt mRNA expression （P<0.05） and significantly lower p-Akt/Akt protein expression （P<0.05）. ConclusionYSJB-containing bone marrow fluid suppresses CD4⁺T-cell migration and regulates Th17/Treg balance by downregulating Th17-associated signature factors and upregulating Treg-associated signature factors through inhibition of the SDF-1/CXCR4 signaling pathway and PI3K/Akt signaling pathway. The SDF-1/CXCR4 signaling pathway is one of the targets through which YSJB inhibits CD4⁺T-cell differentiation.

Objective: To investigate the distribution frequency and molecular mechanism of the rare blood type Lu(a-b-) in Shenzhen, and to compare the polymorphisms of the Lutheran blood group system encoding gene LU and the In (Lu) phenotype-related gene KLF1 among Han Chinese, Indian, and Uyghur populations in Xinjiang. Methods: Serological methods were used to screen the Lu(a-b-) phenotype of blood donors in Shenzhen. Third-generation sequencing was employed to sequence the full-length of the LU and KLF1 genes in Lu (a-b-) phenotype samples as well as the samples from the Han Chinese, Indians, and Uyghur population, followed by analysis of gene haplotypes frequencies. Results: Ten individuals with the Lu(a-b-) phenotype were screened out of 14 367 blood donors in Shenzhen, yielding a frequency of approximately 0.07%. Only 2 cases showed mutations in the coding region of the LU gene, while all individuals showed heterozygous mutations in the coding region of the KLF1 gene. The highest mutation frequencies of the LU and KLF1 genes were observed in the Uyghur population in Xinjiang and the Han Chinese in Shenzhen, respectively. Conclusion: All Lu(a-b-) phenotypes are of the In (Lu) type, and their formation mechanism is mainly related to KLF1 gene mutations. Both the LU and KLF1 genes exhibit significant polymorphism in the Han Chinese, Indians, and Uyghur populations.

ObjectiveTo investigate the mechanisms by which Liuwei Buqi prescription （LWBQ） regulates alveolar macrophage efferocytosis and improves inflammatory responses in rats with chronic obstructive pulmonary disease （COPD） characterized by lung-kidney Qi deficiency based on the nuclear factor erythroid 2-related factor 2 （Nrf2）/macrophage receptor with collagenous structure （MARCO） pathway. MethodsSuccessfully modeled rats were randomly divided into a model group， low-dose LWBQ group （LWBQ-L， 2.25 g·kg^-1·d^-1）， medium-dose LWBQ group （LWBQ-M， 4.5 g·kg^-1·d^-1）， high-dose LWBQ group （LWBQ-H， 9 g·kg^-1·d^-1）， and aminophylline group （AMIN， 50 mg·kg^-1·d^-1）， with 8 rats in each group. Another 8 healthy rats were included as the blank group. Except for the blank group， rats in the remaining groups were subjected to smoke exposure combined with forced swimming， intratracheal lipopolysaccharide （LPS） instillation， and subcutaneous hydrocortisone injection to establish a COPD model with lung-kidney Qi deficiency. After successful modeling， rats were administered different doses of LWBQ or AMIN by gavage. Body weight， fur condition， and oral secretions were observed. Pulmonary function was measured using an animal lung function analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interferon-γ （IFN-γ）， interleukin-6 （IL-6）， interleukin-1 （IL-1）， and tumor necrosis factor-α （TNF-α） in bronchoalveolar lavage fluid （BALF） and serum （SER）. Hematoxylin-eosin （HE） staining was used to examine pathological changes in lung tissue. Giemsa staining was performed to detect eosinophils， basophils， and neutrophils in BALF. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） was used to detect apoptosis in lung tissue. Western blot and real-time polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA expression levels of efferocytosis-related proteins growth arrest-specific gene 6 （GAS6）， milk fat globule-epidermal growth factor 8 （MFG-E8）， and pathway-related proteins Nrf2 and MARCO in lung tissue. ResultsCompared with the blank group， the model group showed reduced food intake， nasal and oral secretions with sputum， and decreased body weight （P<0.01）， decreased peak expiratory flow （PEF） （P<0.01）， increased forced vital capacity （FVC） （P<0.01）， and decreased forced expiratory volume in 0.3 s/forced vital capacity ［FEV0.3/FVC （%）］ （P<0.01）. The expression levels of IFN-γ， IL-6， IL-1， and TNF-α in BALF and SER were increased （P<0.01）. Lung tissue exhibited structural destruction， hyperplasia， inflammatory exudation， increased apoptotic cells， and increased mean optical density （P<0.01）. The protein and mRNA expression levels of GAS6， MFG-E8， and MARCO， as well as Nrf2 mRNA expression， were increased （P<0.01）. Compared with the model group， the LWBQ groups showed increased food intake， reduced nasal and oral secretions with sputum， and increased body weight （P<0.05， P<0.01）. PEF was increased （P<0.01）. FVC was increased in rats treated with low- and medium-dose LWBQ （P<0.01）， and FEV0.3/FVC （%） was increased in rats treated with medium- and high-dose LWBQ （P<0.05， P<0.01）. The expression levels of IFN-γ， IL-6， IL-1， and TNF-α in BALF and SER were decreased （P<0.01）. Lung tissue structure was relatively intact， with improvement in hyperplasia and inflammatory exudation. The number of apoptotic cells in lung tissue was reduced， and mean optical density was decreased （P<0.05， P<0.01）. The protein and mRNA expression levels of efferocytosis-related proteins GAS6 and MFG-E8 and pathway-related proteins Nrf2 and MARCO were increased （P<0.01）. ConclusionLWBQ can alleviate pulmonary and systemic inflammation， improve lung function， and reduce lung tissue damage in rats with COPD characterized by lung-kidney Qi deficiency. The mechanism may be related to enhancement of alveolar macrophage efferocytosis through regulation of the Nrf2/MARCO pathway.

To investigate the clinical characteristics and prognosis of extracranial malignant rhabdoid tumor (eMRT) in children, and to provide a reference for the clinical treatment of this disease.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

ObjectiveTo construct and validate a clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure （CHF），aiming to assist clinical diagnosis and provide tools and methods for individualized treatment of CHF. MethodsThe clinical data of patients with chronic heart failure treated at Dongzhimen Hospital of Beijing University of Chinese Medicine from January 2022 to January 2024 were retrospectively collected. The patients were randomly divided into a training group and a validation group with a ratio of 7∶3. First， the least absolute shrinkage and selection operator （LASSO） regression analysis was used to preliminarily screen the predictive factors affecting the diagnosis of Qi deficiency and blood stasis syndrome in CHF. Subsequently， the Logistic regression method was applied to conduct a more in-depth and detailed analysis of these factors. Variables with P<0.05 in the results of the multi-factor Logistic regression were carefully selected and included. Based on the regression coefficients obtained from this analysis， a model was constructed， and a nomogram was accurately drawn. Using R software，the receiver operating characteristic （ROC） curve，calibration curve，and decision curve analysis （DCA） were precisely drawn. These analyses were used to comprehensively evaluate the model from three crucial aspects： discrimination，calibration，and clinical applicability. Additionally， the accuracy，specificity，sensitivity，positive predictive value，and negative predictive value of the model were meticulously calculated to conduct a more all-round and comprehensive assessment. ResultsIn total， 168 cases were successfully obtained in the training group， and 71 cases were included in the validation group. After a thorough comparison， it was found that there were no statistically significant differences in the baseline data between the two groups. After being rigorously screened by the LASSO-multivariate logistic regression method， dark red tongue，smoking history，cardiac troponin I，and N-terminal pro-B-type natriuretic peptide （NT-ProBNP） were identified as the influencing factors for diagnosing patients with the Qi deficiency and blood stasis syndrome in CHF. The constructed model demonstrated an area under the curve （AUC） of 0.812 in the training group and 0.719 in the validation group. The calibration curve showed that the predicted curve of the model was close to the actual observed curve. DCA indicated that the model could provide substantial clinical benefits for patients at the decision thresholds ranging from 0.2 to 0.9. ConclusionThe clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure constructed in this study shows good performance. It has certain application value in clinical practice， which may contribute to the improvement of the diagnosis and treatment of CHF patients with this syndrome.

OBJECTIVE: This study aimed to explore the interplay between the life-course body mass index (BMI) trajectories and insulin resistance (IR) on incident diabetes. METHODS: This longitudinal cohort included 2,336 participants who had BMI repeatedly measured 3-8 times between 1989 and 2009, as well as glucose and insulin measured in 2009. BMI trajectories were identified using a latent class growth mixed model. The interplay between BMI trajectories and IR on diabetes was explored using the four-way effect decomposition method. Logistic regression and mediation models were used to estimate the interaction and mediation effects, respectively. RESULTS: Three distinct BMI trajectory groups were identified: low-stable ( n = 1,625), medium-increasing ( n = 613), and high-increasing ( n = 98). Both interaction and mediation effects of BMI trajectories and IR on incident diabetes were significant ( P < 0.05). The proportion of incident diabetes was higher in the IR-obesity than in the insulin-sensitivity (IS) obesity group (18.9% vs. 5.8%, P < 0.001). After adjusting for covariates, the odds ratios (95% confidence intervals) of the IR, IS-obesity, and IR-obesity groups vs. the normal group were 3.22 (2.05, 5.16), 2.05 (1.00, 3.97), and 7.98 (5.19, 12.62), respectively. IR mediated 10.7% of the total effect of BMI trajectories on incident diabetes ( P < 0.001). CONCLUSION We found strong interactions and weak mediation effects of IR on the relationship between life-course BMI trajectories and incident diabetes. IS-obesity is associated with a lower risk of incident diabetes than IR-obesity.
Humans ; Insulin Resistance ; Body Mass Index ; Male ; Female ; Middle Aged ; China/epidemiology* ; Adult ; Longitudinal Studies ; Incidence ; Diabetes Mellitus/epidemiology* ; Aged ; Obesity/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; East Asian People

Objective To establishing a chromatographic analysis method for therapeutic drug monitoring of fruquintinib by high-performance liquid chromatography （HPLC）. Methods The analysis was conducted using a Welch Ultimate XB-C₁₈ （4.6 mm×150 mm, 5 μm） column with the column temperature at 35℃. The flow rate was 1.0 ml/min and the detection wavelength was at 240 nm. The mobile phase consisted of acetonitrile and 10 mmol/L potassium dihydrogen phosphate （pH 3.15）= 40∶60（V∶V）. The internal standard substance was Apatinib．All plasma samples were extracted with ethyl acetate solution. Results The linearity of Fruquintinib in plasma was good within the range of 15.63-500.00 ng/ml （r=0.999 9）. The recoveries of the method were between 95%-110% with the RSD less than 10%. The extraction rates of the method were all higher than 97%. The stability tests met the relative requirements. Conclusion A HPLC method for the determination of Fruquintinib in human plasma was established. The method had good specialty, and could be used to detect the blood concentrations of Fruquintinib in clinical practice to improve the individualized medication．