Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

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.

AIM:To explore the role and mechanism of calcium-sensing receptor(CaSR)in regulating macro-phage polarization in hypertensive rats.METHODS:Male spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats were categorized into WKY group,SHR group,SHR+R568(CaSR agonist)group,and SHR+NPS2143(CaSR inhibitor)group.The thoracic aorta was isolated,and the expression of CaSR and macrophage polarization markers in the aorta was observed through immunofluorescence staining.The primary peritoneal macrophages of SHR and WKY rats were aseptically extracted following anesthesia.After intervention with R568 and NPS2143,the expression levels of M1 and M2 markers of peritoneal macrophages were observed by Western blot and immunofluorescence staining.The levels of interleukin(IL)-1β and IL-10 were measured by ELISA.The concentration of Ca2+in peritoneal macrophages was mea-sured by immunofluorescence.Western blot was employed to identify the expression of CaSR and nucleotide-binding oligo-merization domain-like receptor protein 3(NLRP3)inflammasome components.Following anesthesia,vascular smooth muscle cells(VSMCs)were isolated from SHR using an adherent method.Subsequently,a co-culture system was estab-lished with macrophage supernatant.The optimal action time for this co-culture system was determined through CCK-8 as-say.RESULTS:Compared with SHR group,activation of CaSR resulted in a significant decrease in the protein expres-sion of M1 polarization markers(P<0.05)and a concomitant increase in the protein expression of M2 polarization markers in the aorta(P<0.05).Compared with SHR group,administration of R568 led to a significant decrease in the protein ex-pression of M1 polarization markers(P<0.05)and a concomitant increase in the protein expression of M2 polarization markers(P<0.05)in peritoneal macrophages.Additionally,there was a notable reduction in the protein levels of NLRP3 inflammasome components(P<0.05).Furthermore,the fluorescence intensity of intracellular Ca2+was significantly en-hanced following R568 treatment(P<0.05).After administration of MCC950,an NLRP3 inflammasome inhibitor,the re-sults were consistent with those observed following R568 treatment,demonstrating statistical significance(P<0.05).This effect was reversed by the combined intervention of U73122,a phospholipase C(PLC)inhibitor(P<0.05).Compared with the control(0 h),the 24-h peritoneal macrophage supernatant exhibited the strongest capacity to enhance the viabili-ty of VSMCs after 24 h of culture(P<0.05).CONCLUSION:In hypertensive rats,the CaSR inhibits NLRP3 inflamma-some activation via the PLC-Ca2+signaling pathway,thereby mediating an increase in macrophage polarization towards the M2 phenotype and a decrease towards the M1 phenotype.

Objective:The characteristics of D-dimer（D-D），liver enzymes and clinical presentation in pediatric Mycoplasma pneumoniae pneumonia（MPP）complicated by plastic bronchitis（PB）were analyzed,and the predictive value of abnormal D-D and liver enzymes in MPP complicated by PB was discussed.Methods:Patients diagnosed with MPP who underwent bronchoscopy at the Pediatric Department of Shenzhen Baoan Women's and Children's Hospital in Shenzhen between March 2023 and March 2024 were enrolled. The participants were categorized into the PB group and the non-PB group based on the presence or absence of PB complications.The differences in clinical characteristics，treatment characteristics，laboratory results and imaging results between the two groups were compared.The nomogram prediction model of MPP combined with PB was established,and its effectiveness was evaluated.Results:A total of 225 pediatric patients were enrolled,including 52 cases in the PB group and 173 cases in the non-PB group. No statistically significant differences were observed between the two groups in baseline characteristics such as age, gender, and body weight ( P>0.05).The PB group had a higher proportion of respiratory distress, respiratory support, PICU admission, decreased of SpO 2, viral infection and bacterial infection. And neutrophil ratio, C-reactive protein,procalcitonin, coagulation index and liver enzyme index were significantly higher than those in non-PB group.The analysis of binary Logistic analysis showed that increased aspartic transaminase, increased D-D,and the need of respiratory support were independent risk factors for MPP combined with PB.The nomogram predictive model based on binary Logistic analysis showed that the area under curve for predicting MPP combined with PB was 0.800（95% CI 0.724-0.875， P<0.001）.The calibrate curve showed that the predicted probability of the model fit well with actual probability. Conclusion:Children with MPP complicated by PB have higher levels of aspartic transaminase and D-D,along with an increased proportion requiring repiratory support.The prediction model based on these indicators shows good clinical application value.

Objective:To evaluate the current situation of the protective effect of hearing protection device (HPD) worn by manufacturing workers and discuss their possible influencing factors.Methods:A total of 3634 noisy workers were surveyed and tested. The study conducted surveys of workers on the use of HPD. The 3M TM E-A-R Fit TM binaural verification system was used to measure the personal attenuation device (PAR) of workers wearing HPD. Results:The M ( Q1, Q3) of baseline PAR obtained by 3634 workers was 12 (2, 19) dB. There was a statistically significant difference in baseline PAR among the three types of HPDs ( H=336.39, P<0.01) . After pairwise comparison, it was found that the baseline PAR of workers wearing foam earplugs and earmuffs was higher than that of pre-molded earplugs ( P<0.01) . There were differences in baseline PAR among workers in different industries ( Z=359.73, P<0.01) . Education level, age of using HPD, types of HPDs, noise exposure intensity, with or without knowledge of correct methods, and comfort evaluation were the main factors affecting baseline PAR ( P<0.05) . There were 1536 workers (43.4%) failed the baseline PAR test. After the intervention, the median PAR increased significantly from 1 (0, 6) dB (baseline) to 18 (14, 22) dB (after the intervention) ( P<0.01) . The follow-up test found that the follow-up PAR of 328 workers was higher than the baseline PAR of the initial test, and the follow-up PAR was higher than the post-intervention PAR of the initial test ( P<0.01) . Conclusion:Under the conditions of this study, the protective effect of HPD was affected by factors such as incorrect understanding of wearing methods, exposure to high-intensity noise, low education level, a short period of time of HPD use and low comfort of hearing protectors. The protective effect could be improved through training, optimizing the wearing of hearing protector models, and follow-up interventions. Enterprises should use suitability verification to ensure the correct selection and wearing of noisy workers.

Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.

Objective To explore the different potential subtypes of psychosocial adaptation among young and middle-aged stroke patients,and analyze the relationship between different potential subtypes and quality of life,so as to provide references for the subsequent development of targeted interventions.Methods A total of 406 young and middle-aged stroke patients in 4 tertiary hospitals in Suzhou from June 2023 to June 2024 were recruited by convenience sampling.The General Information Questionnaire,the Self-Report Psychosocial Adjustment to Illness Scale and the EuroQol five-dimensional questionnaire were conducted for investigation.Latent profile analysis was used to explore the potential subtypes of psychosocial adaptation among young and middle-aged stroke patients.Generalized linear regression analysis was conducted with quality of life as dependent variables.Results A total of 380 young and middle-aged stroke patients were included.The psychosocial adaptation of patients could be classified into 3 potential subtypes:high adaptation level type(23.90％),medium adaptation level with health concerns type(46.40％),and low adaptation level with psychological barriers type(29.70％).The results of generalized linear regression analysis showed that potential subtypes of psychosocial adaptation were the influencing factors for quality of life in young and middle-aged stroke patients(P＜0.05).Conclusion There was group heterogeneity in psychosocial adaptation among young and middle-aged stroke patients,and the potential subtype of psychosocial adaption was an important factor affecting the quality of life of patients.It is suggested that medical staff should focus on patients with low adaptation level with psychological barriers type,and take targeted interventions according to characteristics of different subtypes of patients,so as to improve their quality of life.