The diagnostic frequency of multiple pulmonary tumor nodules has increased significantly in clinical practice. Among patients with multiple pulmonary nodules, distinguishing between separate primary lung carcinomas and intrapulmonary metastases is critical for accurate tumor staging, therapeutic decision-making, and prognostic evaluation. The consensus document "Differentiating separate primary lung adenocarcinomas from intrapulmonary metastases with emphasis on pathological and molecular considerations: Recommendations from the International Association for the Study of Lung Cancer Pathology Committee" highlights the pivotal role of integrated pathological and molecular analyses in diagnosing and differentiating primary lung adenocarcinomas from intrapulmonary metastatic lesions. It further proposes a combined four-step histologic and molecular classification algorithm for addressing multiple pulmonary tumor nodules of adenocarcinoma histology, providing clinicians with enhanced diagnostic tools to refine staging accuracy, guide therapeutic strategies, and improve prognostic predictions for lung adenocarcinoma. Building on current advancements in global research, this article offers a comprehensive interpretation of the consensus recommendations.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

Objective To explore the correlation and dose-response relationship between blood lipid parameters and the risk of thyroid nodules (TNs) in euthyroid women, providing references for disease prevention. Methods A case-control study was conducted, including 1 412 euthyroid women (701 in the case group and 711 in the control group). Crude and multivariable logistic regression models were used to assess the association between blood lipid parameters and the risk of TNs, and restricted cubic spline regression was applied to explore the dose-response relationship. Results Compared with women in the lowest quartile of serum triglyceride (TG; Q1, TG≤0.92 mmol/L), the risk of TNs was 45% (OR＝1.45, 95%CI 1.06-1.98) higher for those in Q2 (TG 0.93-1.24 mmol/L), 101% (OR＝2.01, 95%CI 1.47-2.77) higher for those in Q3 (TG 1.25-1.81 mmol/L), and 67% (OR＝1.67, 95%CI 1.19-2.33) higher for those in Q4 (TG>1.81 mmol/L) after adjusting for age, body mass index (BMI) and education. For each unit increase in log₁₀TG, the risk increased by 98% (OR＝1.98, 95%CI 1.14-3.45). Moreover, the correlation remained statistically significant even after further adjustment for thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) and urinary iodine (OR＝1.75, 95%CI 1.00-3.06, P＜0.05). However, correlations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with the risk of TNs were not statistically significant. Restricted cubic spline regression analysis further demonstrated the non-linear dose-response relationship of TG levels with the risk of TNs. Specifically, the risk of TNs increased in a monotonic manner at lower TG concentrations (＜1.23 mmol/L), but appeared to plateau or even slightly decrease at higher levels of TG (≥1.23 mmol/L). Conclusions Among euthyroid women, higher serum TG level is associated with risk of TNs, and this correlation is non-linear.

Objective To characterize the features of patent foramen ovale(PFO)-related cryptogenic stroke using diffusion-weighted imaging(DWI)and to investigate the correlation between infarct size and cardiac CT characteristics of PFO.Methods A retrospective,consecutive cohort study was conducted on acute ischemic stroke patients admitted to Neurology Department of Xuanwu Hospital,Capital Medical University from January 2022 to September 2024.Patients were categorized into PFO group,arterio-arterial embolism(AAE)group,and atrial fibrillation(AF)group based on etiological diagnosis.Baseline clinical data,including age,height,body mass index,admission National Institutes of Health stroke scale(NIHSS)score,history of old cerebral infarction,hypertension,diabetes mellitus,coronary heart disease,dyslipidemia,and smoking history were collected and compared.All patients underwent head MR within 24 h of admission.DWI was used to analyze and compare infarct characteristics across the three groups,including lesion number(single or multiple),location(cortical+subcortical,deep white matter,cortical+subcortical+deep white matter,cerebellum+thalamus+brainstem),size(≥15 mm or＜15 mm,based on maximum transverse diameter;for multiple lesions,if any lesion had a maximum diameter≥15 mm,it was categorized as≥15 mm),infarcted vascular territory(anterior,posterior,or both circulations),and specific arterial supply(anterior cerebral artery,middle cerebral artery,posterior cerebral artery,basilar artery,posterior inferior cerebellar artery,superior cerebellar artery,anterior choroidal artery,or multiple arteries).Patients in the PFO group additionally underwent cardiac CT to measure PFO-related parameters:tunnel length,width,height,septum secundum thickness,and fossa ovalis length.Spearman correlation analysis was performed to evaluate the relationship between infarct size and PFO cardiac CT features.Results A total of 232 acute ischemic stroke patients were included(mean age[57±17]years,ranged 19-86 years;141 males,91 females),comprising 116 in the PFO group,36 in the AAE group,and 80 in the AF group.(1)The proportion of males in the PFO group was higher than that in the AF group,it was lower than that in the AAE group.The age,body mass index and proportions of patients with hypertension,diabetes,hyperlipidemia,coronary heart disease were all lower than those in the other two groups(both P＜0.016 7),while other baseline characteristics showed no significant differences(all P＞0.05).(2)The PFO group exhibited a higher proportion of multiple infarcts compared to the AAE group(83.62％[97/116]vs.61.11％[22/36],P＜0.016 7),but a lower proportion than the AF group(83.62％[97/116]vs.98.75％[79/80],P＜0.016 7).The PFO group also showed a significantly higher proportion of cortical+subcortical infarcts(47.41％[55/116]vs.11.11％[4/36]and 6.25％[5/80],respectively,both P＜0.016 7)and infarcts with a maximum diameter＜15 mm compared to both AAE and AF groups(66.38％[77/116]vs.36.11％[13/36]and 11.25％[9/80],respectively,both P＜0.016 7).Furthermore,the PFO group had a lower proportion of anterior circulation infarcts(27.59％[32/116]vs.69.44％[25/36]in AAE group and 67.50％[54/80]in AF group,both P＜0.016 7),but a higher proportion of posterior circulation infarcts(62.07％[72/116]vs.16.67％[6/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).Specifically,middle cerebral artery infarcts were less common in the PFO group(18.97％[22/116]vs.66.67％[24/36]in AAE group and 52.50％[42/80]in AF group,both P＜0.016 7),while posterior cerebral artery infarcts were more common(48.28％[56/116]vs.8.33％[3/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).(3)Spearman correlation analysis revealed that infarct size was negatively correlated with PFO tunnel length(rs=-0.429,P=0.029),fossa ovalis length(rs=-0.408,P=0.038),and septum secundum thickness(rs=-0.525,P=0.006),but not correlated with PFO width or height(both P＞0.05).Conclusions PFO-related cryptogenic stroke is predominantly characterized by multiple small infarcts,primarily located in the cortical+subcortical regions and posterior circulation.Infarct size was found to be negatively correlated with PFO tunnel length,fossa ovalis length,and septum secundum thickness.Comprehensive assessment integrating DWI and cardiac CT features may facilitate the identification of PFO-related stroke.These findings warrant further validation through larger,prospective studies.

The integration of traditional Chinese and Western medicine is a crucial contemporary medical model widely utilized today.Modern medicine is intricately linked to"data"and"calculation".The key to the high-quality development of integrated Chinese and Western medicine is to realise the in-depth integration of information technology and modern medicine,including tackling the three major scientific problems(algorithm establishment,queue creation and data quality),introducing laws and policies,fostering cross-innovation talents in integrated Chinese and Western medicine,and regulating standards.At the same time,adhering to the principle of integrity and innovation,and being firm in cultural self-confidence are important factors in promoting the healthy,rapid and sustainable development of the cause of integrative Chinese and Western medicine and traditional Chinese medicine.

Wound healing is a dynamic physiological process involving haemostasis,inflammation,pro-liferation and tissue remodeling.Skin injuries,such as diabetic foot ulcers,venous ulcers,and pressure ulcers,are difficult to heal and impose a serious physical and psychological burden on patients,and tra-ditional treatments are difficult to address such problems.In recent years,Chinese herbal medicine-de-rived extracellular vesicles(CHMEVs)have shown promising potential in the field of wound repair and drug delivery due to their excellent biocompatibility,low immunogenicity and high safety.CHMEVs are nano-like particles enriched with herbal small molecule compounds,proteins and metabolites,and are a-ble to cross biological barriers and effectively regulate intercellular communication to promote tissue re-pair.In this review,the isolation and extraction methods of CHMEVs and their roles in wound repair are reviewed,and the prospects and challenges of their clinical applications are discussed.The combination of engineered modification and biomaterials of CHMEVs further expands their potential for application in precision medicine and provides a new idea for the treatment of hard-to-heal wounds in the future.

Objective:To investigate the molecular mechanisms of bexarotene in treating double hit lymphoma(DHL)based on Weighted Gene Co-expression Network Analysis(WGCNA),thereby providing potential targets and experimental evidence for DHL treatment.Methods:The gene expression datasets GSE44164 and GSE43677 were downloaded from the Gene Expression Omnibus(GEO)database,and differentially expressed genes(DEGs)were identified.WGCNA was employed to identify gene modules associated with DHL.A protein-protein interaction(PPI)network was constructed to screen for key hub genes.Drug-gene association analysis was conducted using the EpiMed platform to identify potential targeted drugs for DHL.The effects of bexarotene on DHL cell proliferation and key protein expression were evaluated using the CCK-8 assay and Western blotting(WB),and its effects on cell apoptosis was evaluated using flow cytometry.Results:WGCNA identified a turquoise module highly associated with DHL,and 10 hub genes(COL1A2,COL3A1,MMP2,COL5A2,DCN,BGN,FN1,MMP9,FBN1,and LUM)were screened from the PPI network.Drug association analysis nominated bexarotene as a potential therapeutic agent.In vitro validation demonstrated that bexarotene significantly inhibited U2932 cell viability(P<0.05),promoted cell apoptosis(P<0.001),and downregulated c-Myc and COL1A2 expression(P<0.05).Conclusion:Bexarotene may exert anti-DHL effects by suppressing the c-Myc signaling pathway and modulating extracellular matrix-related genes.Further studies are warranted to validate its in vivo efficacy and potential for combination therapy.

Wound healing is a dynamic physiological process involving haemostasis,inflammation,pro-liferation and tissue remodeling.Skin injuries,such as diabetic foot ulcers,venous ulcers,and pressure ulcers,are difficult to heal and impose a serious physical and psychological burden on patients,and tra-ditional treatments are difficult to address such problems.In recent years,Chinese herbal medicine-de-rived extracellular vesicles(CHMEVs)have shown promising potential in the field of wound repair and drug delivery due to their excellent biocompatibility,low immunogenicity and high safety.CHMEVs are nano-like particles enriched with herbal small molecule compounds,proteins and metabolites,and are a-ble to cross biological barriers and effectively regulate intercellular communication to promote tissue re-pair.In this review,the isolation and extraction methods of CHMEVs and their roles in wound repair are reviewed,and the prospects and challenges of their clinical applications are discussed.The combination of engineered modification and biomaterials of CHMEVs further expands their potential for application in precision medicine and provides a new idea for the treatment of hard-to-heal wounds in the future.

Objective:To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms.Methods:A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group ( n=6), FLASH irradiation groups ( n=90), and CONV irradiation groups ( n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results:After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group ( t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group ( P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy ( t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy ( t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant ( tcrypt=13.10, 23.80, 11.90; tmucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ2=5.39, P<0.05), with a median survival extension of 6 d ( HR=0.340, 95% CI: 0.115 4-0.999 9). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy ( P>0.05). Conclusions:FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.