Objective To construct a lung cancer surgery-oriented disease-specific database covering the entire perioperative care pathway, thereby improving the quality and usability of key surgical data elements. Methods Real-world clinical data were extracted from a single-center thoracic surgery department. A standardized data model was established based on the open electronic health record (openEHR) standard. Large language model (LLM), optical character recognition (OCR), and artificial intelligence (AI)-driven techniques were employed to extract, structure, and perform quality control on unstructured clinical narratives, imaging reports, and radiological data, with a focus on capturing surgically relevant perioperative indicator. Results A multimodal database comprising 19 917 patients was established, including 7 930 males and 11 987 females, with ages ranging from 15 to 97 (61.7±9.7) years. The database includes 582 structured data variables, textual report data corresponding to 69 clinical indicators, 13 000 pulmonary function test PDF reports, and chest CT imaging data from 16 884 patients. This database comprehensively covers major information relevant to surgical diagnosis and treatment of lung cancer, significantly improving the completeness and granularity of surgical detail data. Large language models (LLMs) and optical character recognition (OCR) technologies enhanced the efficiency of converting unstructured data into structured formats, while a multi-level manual verification process ensured data accuracy and traceability. The database supports real-world research including comparisons of surgical procedures, prediction of postoperative complications, prognosis assessment, and multimodal data association analyses.

Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE: To compare the bone cement diffusion and clinical effects between conventional percutaneous vertebroplasty(PVP) and the application of positioning reduction and targeted puncture techniques in the treatment of elderly patients with osteoporotic vertebral compression fractures. METHODS: A retrospective comparative study was conducted, analyzing the clinical data of 268 elderly patients with single-level vertebral fractures admitted between January 2021 and March 2023. The patients were divided into two groups:the conventional PVP group (138 cases) and the targeted PVP group (130 cases). Among them, 138 patients in the conventional group were treated by traditional PVP with bilateral approach including 26 males and 112 females, with a mean age of (72.9±4.0) years old. Another 130 patients in the targeted PVP group included 23 males and 107 females, with a mean age of (72.2±7.0) years old;vertebral reduction was first achieved using prone traction and compression reduction technique based on preoperative imaging examination, the operating bed was used to maintain spinal hyper-extension of the spine and puncture the fracture space target to inject bone cement. The adequacy of bone cement filling in the fracture gap was evaluated based on imaging examination. The operation time, the rate of bone cement leakage and the type of leakage, bone cement filling in the fracture area, the amount of cement injection, the thoracolumbar back pain visual analogue scale(VAS), Oswestry disability index(ODI), and the local kyphosis Cobb angle of the fractured vertebra were compared between two groups. RESULTS: The operation time (43.9±5.7) min, bone cement filling (5.3±1.5) ml in the conventional PVP group were higher than the target group (39.3±3.6) min, (4.1±1.7) ml(P<0.05). There were no statistically significant differences in bone cement leakage rate or type(P>0.05). The targeted PVP group achieved sufficient bone cement filling in the fracture area, while the conventional PVP group had 34 cases (25.0%) with insufficient filling in the fracture area(P<0.01). There was no significant difference in VAS, ODI, and local Cobb angle of the fractured vertebra before operation between two groups(P>0.05). The VAS of 3.64±0.94 and ODI of 11.50±0.38 at 3 day after operation in the target group were better than those of the conventional group 4.69±0.78 and 15.06±1.66 (P<0.05). The local Cobb angle (7.51±5.37)° was less than that of the conventional group (11.68±3.98)°(P<0.05). CONCLUSION The application of positioning reduction and targeted puncture techniques in percutaneous vertebroplasty for elderly patients with osteoporotic vertebral compression fractures can restore vertebral height using positioning reduction technique to avoid excessive tension on the intervertebral soft tissue. Targeted puncture technique effectively stabilizes vertebral fractures and achieves adequate bone cement filling, thereby improving surgical outcomes. This technique is safe and effective, representing a new treatment modality.
Humans ; Male ; Female ; Vertebroplasty/methods* ; Aged ; Fractures, Compression/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Aged, 80 and over ; Bone Cements ; Middle Aged

OBJECTIVE: To explore the epidemiological characteristics of knee osteoarthritis (KOA) among the elderly in the community, and its correlation with bone mass loss. METHODS: A cross-sectional study was conducted on elderly community population over 50 year old from 12 community health service centers in Zhejiang province. Their gender, age, body mass index (BMI), T value and KOA diagnosis were collected using face to face questionnaire survey. Univariate regression was used to analyze the influence of age, gender, BMI and bone loss on KOA. Logistic multivariate regression model was used to analyze the independent effect of bone mass loss on KOA. RESULTS: Among 4 173 subjects in this study, 1 710 of them were had a KOA. The prevalence rate was 40.9%. The mean age, the proportion of females and the mean BMI in KOA patients were (65.5±3.8) years old, 67.7%(1 158/1 710) and(24.59±1.28) kg·m^-2, respectively, which were significantly higher than (58.5±3.2) years old, 51.3%(1 263/2 463), and (23.48±1.25) kg·m^-2 in non-KOA subjects (P<0.001). In the population aged from 60 to 69 years old, the influence of osteopenia and osteoporosis on the prevalence of KOA was[OR=1.21, 95%CI(1.00, 1.46), P=0.053 2], [OR=1.42, 95%CI(1.14, 1.78), P=0.002 2]. The influence of male and female osteoporosis on the prevalence of KOA was [OR=1.52, 95%CI(1.16, 1.99), P=0.002 7] and [OR=1.87, 95%CI(1.51, 2.32), P<0.000 1], respectively. In the population of 24 kg·m^-2≤BMI<28 kg·m^-2, the influence of osteopenia and osteoporosis on the prevalence of KOA was [OR=1.47, 95%CI(1.21, 1.80), P=0.000 1], [OR=2.69, 95%CI(2.11, 3.42), P<0.000 1], respectively. After controlling the confounding factors of age, gender and BMI, compared with people with normal bone mass, the effect of osteopenia on the prevalence of KOA was [OR=1.34, 95%CI(1.08, 1.67), P=0.009 2], and the effect of osteoporosis on the prevalence of KOA was [OR=1.38, 95%CI(1.06, 1.79), P=0.017 9]. CONCLUSION Elderly overweight women are more likely to develop KOA. Bone mass loss is an independent risk factor for KOA, which will significantly increase the prevalence of KOA in people overweight or aged 60 to 69 years old.
Humans ; Female ; Male ; Aged ; Osteoarthritis, Knee/etiology* ; Middle Aged ; Cross-Sectional Studies ; Bone Density ; Aged, 80 and over ; Incidence ; Body Mass Index ; China/epidemiology* ; Osteoporosis/epidemiology*

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.