Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2＜BMI≤23 kg/m2), a group B (23 kg/m2＜BMI≤29 kg/m2) and a group C (BMI＞29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.

ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery， and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio （INR） after taking mifepristone， clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes； for the selection of sex hormones after missed abortion， clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment， supplemented by Xian yimucao capsules， to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge， and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery， mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans， identification of drug-drug interactions， assessment of bleeding risks， and selection of postoperative sex hormones. Through full pharmaceutical monitoring， they ensure the safety of patients’ medication.

OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery， and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio （INR） after taking mifepristone， clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes； for the selection of sex hormones after missed abortion， clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment， supplemented by Xian yimucao capsules， to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge， and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery， mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans， identification of drug-drug interactions， assessment of bleeding risks， and selection of postoperative sex hormones. Through full pharmaceutical monitoring， they ensure the safety of patients’ medication.

Objective To investigate whether Danshen injection (DSI) can protect human brain organoids from oxidative stress damage by regulating the Nrf2 signaling pathway and its mechanism. Methods A Nrf2 plasmid was constructed, lentivirus was packaged and transfected into human induced pluripotent stem cell (hiPSC) to form a stable cell line. Brain organoids with Nrf2 overexpression (LV-Nrf2 group) and knockdown (sh-Nrf2 group) were constructed using kit. The transfection efficiency was verified by real-time fluorescence quantitative polymerase chain reaction. An oxidative stress injury model was established by inducing hydrogen peroxide (H₂O₂). Intervention was performed either in combination or without DSI pre-treatment. Cell viability was detected by Cell Counting Kit-8 (CCK-8), and the expression levels of Nrf2, malondialdehyde (MDA), interleukin (IL)-1β, sex-determining region Y-box protein 2 (SOX2) and neuronal-specific nuclear protein (NeuN) were detected by Western blot and immunofluorescence staining. Total RNA from human brain organoids was extracted for transcriptome sequencing and analysis. Results LV-Nrf2 group and sh-Nrf2 group brain organoid models were successfully constructed. The CCK-8 results determined that the oxidative stress model was established with 32 mmol/L H₂O₂ intervention conditions. The fluorescence expression of Nrf2 in LV-Nrf2 group was higher than that in control group, and the fluorescence expressions of MDA and IL-1β were lower than those in control group; sh-Nrf2 group showed a damage phenotype of low Nrf2 expression, high MDA and IL-1β expression (all P < 0.05). Compared with H₂O₂ group, the Nrf2 signal in DSI + H₂O₂ group was stronger, and the levels of MDA and IL-1β were lower. Among them, the protective effect of LV-Nrf2 was the most significant. H₂O₂ treatment could down-regulate the protein levels of Nrf2, SOX2 and NeuN, and DSI intervention could effectively reverse the downward trend of these indicators. Sh-Nrf2 could weaken the recovery effect of DSI on SOX2 and NeuN, while LV-Nrf2 could synergistically enhance the regulatory effect of DSI. Conclusions DSI may antagonize oxidative stress damage in human brain organoids through the Nrf2 signaling pathway, and maintaining the stability of the neural cell lineage is its core therapeutic characteristic.

Objective To predict the lymph node metastasis status of patients with invasive pulmonary adenocarcinoma by constructing machine learning models based on primary tumor radiomics, peritumoral radiomics, and habitat radiomics, and to evaluate the predictive performance and generalization ability of different imaging features. Methods A retrospective analysis was performed on the clinical data of 1 263 patients with invasive pulmonary adenocarcinoma who underwent surgery at the Department of Thoracic Surgery, Jiangsu Province Hospital, from 2016 to 2019. Habitat regions were delineated by applying K-means clustering (average cluster number of 2) to the grayscale values of CT images. The peritumoral region was defined as a uniformly expanded area of 3 mm around the primary tumor. The primary tumor region was automatically segmented using V-net combined with manual correction and annotation. Subsequently, radiomics features were extracted based on these regions, and stacked machine learning models were constructed. Model performance was evaluated on the training, testing, and internal validation sets using the area under the receiver operating characteristic curve (AUC), F1 score, recall, and precision. Results After excluding patients who did not meet the screening criteria, a total of 651 patients were included. The training set consisted of 468 patients (181 males, 287 females) with an average age of (58.39±11.23) years, ranging from 29 to 78 years, the testing set included 140 patients (56 males, 84 females) with an average age of (58.81±10.70) years, ranging from 34 to 82 years, and the internal validation set comprised 43 patients (14 males, 29 females) with an average age of (60.16±10.68) years, ranging from 29 to 78 years. Although the habitat radiomics model did not show the optimal performance in the training set, it exhibited superior performance in the internal validation set, with an AUC of 0.952 [95%CI (0.87, 1.00)], an F1 score of 84.62%, and a precision-recall AUC of 0.892, outperforming the models based on the primary tumor and peritumoral regions. Conclusion The model constructed based on habitat radiomics demonstrated superior performance in the internal validation set, suggesting its potential for better generalization ability and clinical application in predicting lymph node metastasis status in pulmonary adenocarcinoma.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.