Diabetic foot is one of the most common complications in patients with diabetes,potentially resulting in amputation and significant psychological distress.Macrophages and neutrophils play a crucial synergistic role in the inflammatory response;however,an imbalance in this synergy can lead to abnormal inflammatory responses and subsequent tissue damage.Therefore,a comprehensive study of the interactions between macrophages and neutrophils,along with their specific mechanisms in the occurrence and development of diabetic foot,is conducive to developing new therapeutic strategies to improve the clinical prognosis for diabetic patients.This article reviews the research progress on the mechanism of macrophage and neutrophil dysfunction in diabetic foot,in order to provide new ideas and directions for the treatment of diabetic foot.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

Objective:To analyze the distribution characteristics of sports facilities in China using geographic information system (ArcGIS) and to investigate their association with mortality risk among residents.Methods:This prospective cohort study included 97 912 community residents from the Chinese Family Database (CFD) between 2013 and 2017. After excluding participants lost to follow-up and those with incomplete data, 53 937 individuals were retained for the analysis. The distribution characteristics of sports facilities in China was mapped using ArcGIS, and the death events were recorded via structured interviews and questionnaires. The Poisson regression was used to assess the association between the distribution characteristics of sports facilities near participants′ residences and their mortality risk.Results:In 2013, a total of 79 714 sports facilities were identified across 262 districts (counties) in China, with large-scale sports facilities accounting for the highest proportion (87.09%). The median number of sports facilities within the residential buffer zone was 17 (4, 30), and the median distance from the residence to the nearest sports facility was 453.2 (341.5, 1 863.5) m. Among the 53 937 community residents analyzed in this study, there were 27 761 males and 26 176 females, 1 326 deaths (2.5%) occurred during the follow-up. Poisson regression revealed that a higher number of sports facilities in the buffer zone (≥21 vs 0-2) was associated with lower mortality risk ( RR=0.74, 95% CI: 0.64-0.85; P0.05). Subgroup analyses showed that being≥60 years old ( RR=0.82, 95% CI: 0.70-0.95), males ( RR=0.78, 95% CI: 0.64-0.95), females ( RR=0.79, 95% CI: 0.64-0.97), having a junior high school education or less ( RR=0.84, 95% CI: 0.71-0.99), and having a urban residence ( RR=0.77, 95% CI: 0.66-0.90) were all negatively associated with residents′ mortality risk (all P0.05). After adjusting for age, greater distance to the nearest sports facility ( RR=1.41, 95% CI: 1.08-1.83) and failing to meet the"10-minute fitness circle"criterion ( RR=1.25, 95% CI: 1.02-1.53) were associated with higher mortality risk among males (both P0.05). After adjusting for age and gender, urban residents with a greater distance to the nearest sports facility ( RR=1.29, 95% CI: 1.04-1.60) or not meeting the 10-minute fitness circle ( RR=1.18, 95% CI: 1.00-1.38) showed a significantly higher mortality risk (both P0.05). Conclusions:The ArcGIS analysis revealed that the distribution of sports facilities in China is characterized by a high proportion of large-scale facilities. Lower facility density within residential buffer zone and greater distance to the nearest facility increase mortality risk among adults.

In recent years,immune checkpoint inhibitor(ICI)has led to substantial advances in the treatment of recurrent or metastatic advanced cutaneous melanoma(CM),significantly prolonging overall survival.However,due to the biological heterogeneity across melanoma subtypes,the degree of immune responsiveness varies considerably.In particular,acral melanoma(AM)(the predominant melanoma subtype in Asian populations,including China)has demonstrated limited benefit from ICI therapy,especially in the context of monotherapy.Currently,no systematic staging and standardized treatment guidelines are available for AM,and clinical evidence supporting the use of ICI in this rare subtype remains insufficient.In the neoadjuvant setting,several large phase Ⅱ/Ⅲ international trials in CM,including SWOG 1801 and NADINA,have shown that ICI-based neoadjuvant combination therapy significantly improves pathological response rates compared with traditional adjuvant approaches.Nevertheless,neoadjuvant treatment in AM remains in the exploratory stage.Early-phase clinical studies in resectable stage Ⅲ/Ⅳ AM suggest that toripalimab combined with intratumoral oncolytic virus therapy,or camrelizumab in combination with apatinib and temozolomide,may offer clinical benefit;however,confirmation of long-term survival benefit requires further validation in larger,prospective cohorts.In the adjuvant setting,for AM patients with BRAF mutations,real-world data from China have shown no significant difference in survival outcomes between dabrafenib plus trametinib and programmed death-1(PD-1)inhibitor monotherapy in high-risk resectable stage Ⅲ/Ⅳ disease,although direct head-to-head comparisons are lacking.For patients with resectable stage Ⅲ/Ⅳ wild-type AM,combination adjuvant regimens incorporating PD-1 inhibitors may provide superior recurrence risk reduction and survival benefit compared to monotherapy.In the advanced disease setting,in Chinese populations,the objective response rates of PD-1 inhibitors such as pembrolizumab,toripalimab and penpulimab remain suboptimal in AM.ICI-based combination strategies(including those with chemotherapy,anti-angiogenic agents,dual or triple immune checkpoint blockade)may improve the immune microenvironment and clinical prognosis,but concerns regarding safety and tolerability persist.For patients with ICI-refractory AM,various novel approaches combining immunotherapy,targeted agents and chemotherapy are under investigation.Additionally,several next-generation immunotherapeutic modalities[including T-cell receptor-engineered(TCR-T)therapies,therapeutic cancer vaccines,chimeric antigen receptor T(CAR-T)cell therapy and antibody-drug conjugate(ADC)]are currently in development.This review aimed to provide a comprehensive overview of current clinical evidence on the use of ICI in acral melanoma across the neoadjuvant,adjuvant,and advanced disease settings.We highlighted the efficacy and safety of existing strategies,exploreed emerging combination regimens and predictive biomarkers,and discussed key areas for future research to inform clinical decision-making and optimize outcomes in this challenging melanoma subtype.

In recent years,immune checkpoint inhibitor(ICI)has led to substantial advances in the treatment of recurrent or metastatic advanced cutaneous melanoma(CM),significantly prolonging overall survival.However,due to the biological heterogeneity across melanoma subtypes,the degree of immune responsiveness varies considerably.In particular,acral melanoma(AM)(the predominant melanoma subtype in Asian populations,including China)has demonstrated limited benefit from ICI therapy,especially in the context of monotherapy.Currently,no systematic staging and standardized treatment guidelines are available for AM,and clinical evidence supporting the use of ICI in this rare subtype remains insufficient.In the neoadjuvant setting,several large phase Ⅱ/Ⅲ international trials in CM,including SWOG 1801 and NADINA,have shown that ICI-based neoadjuvant combination therapy significantly improves pathological response rates compared with traditional adjuvant approaches.Nevertheless,neoadjuvant treatment in AM remains in the exploratory stage.Early-phase clinical studies in resectable stage Ⅲ/Ⅳ AM suggest that toripalimab combined with intratumoral oncolytic virus therapy,or camrelizumab in combination with apatinib and temozolomide,may offer clinical benefit;however,confirmation of long-term survival benefit requires further validation in larger,prospective cohorts.In the adjuvant setting,for AM patients with BRAF mutations,real-world data from China have shown no significant difference in survival outcomes between dabrafenib plus trametinib and programmed death-1(PD-1)inhibitor monotherapy in high-risk resectable stage Ⅲ/Ⅳ disease,although direct head-to-head comparisons are lacking.For patients with resectable stage Ⅲ/Ⅳ wild-type AM,combination adjuvant regimens incorporating PD-1 inhibitors may provide superior recurrence risk reduction and survival benefit compared to monotherapy.In the advanced disease setting,in Chinese populations,the objective response rates of PD-1 inhibitors such as pembrolizumab,toripalimab and penpulimab remain suboptimal in AM.ICI-based combination strategies(including those with chemotherapy,anti-angiogenic agents,dual or triple immune checkpoint blockade)may improve the immune microenvironment and clinical prognosis,but concerns regarding safety and tolerability persist.For patients with ICI-refractory AM,various novel approaches combining immunotherapy,targeted agents and chemotherapy are under investigation.Additionally,several next-generation immunotherapeutic modalities[including T-cell receptor-engineered(TCR-T)therapies,therapeutic cancer vaccines,chimeric antigen receptor T(CAR-T)cell therapy and antibody-drug conjugate(ADC)]are currently in development.This review aimed to provide a comprehensive overview of current clinical evidence on the use of ICI in acral melanoma across the neoadjuvant,adjuvant,and advanced disease settings.We highlighted the efficacy and safety of existing strategies,exploreed emerging combination regimens and predictive biomarkers,and discussed key areas for future research to inform clinical decision-making and optimize outcomes in this challenging melanoma subtype.

Diabetic foot is one of the most common complications in patients with diabetes,potentially resulting in amputation and significant psychological distress.Macrophages and neutrophils play a crucial synergistic role in the inflammatory response;however,an imbalance in this synergy can lead to abnormal inflammatory responses and subsequent tissue damage.Therefore,a comprehensive study of the interactions between macrophages and neutrophils,along with their specific mechanisms in the occurrence and development of diabetic foot,is conducive to developing new therapeutic strategies to improve the clinical prognosis for diabetic patients.This article reviews the research progress on the mechanism of macrophage and neutrophil dysfunction in diabetic foot,in order to provide new ideas and directions for the treatment of diabetic foot.

Objective:To analyze the distribution characteristics of sports facilities in China using geographic information system (ArcGIS) and to investigate their association with mortality risk among residents.Methods:This prospective cohort study included 97 912 community residents from the Chinese Family Database (CFD) between 2013 and 2017. After excluding participants lost to follow-up and those with incomplete data, 53 937 individuals were retained for the analysis. The distribution characteristics of sports facilities in China was mapped using ArcGIS, and the death events were recorded via structured interviews and questionnaires. The Poisson regression was used to assess the association between the distribution characteristics of sports facilities near participants′ residences and their mortality risk.Results:In 2013, a total of 79 714 sports facilities were identified across 262 districts (counties) in China, with large-scale sports facilities accounting for the highest proportion (87.09%). The median number of sports facilities within the residential buffer zone was 17 (4, 30), and the median distance from the residence to the nearest sports facility was 453.2 (341.5, 1 863.5) m. Among the 53 937 community residents analyzed in this study, there were 27 761 males and 26 176 females, 1 326 deaths (2.5%) occurred during the follow-up. Poisson regression revealed that a higher number of sports facilities in the buffer zone (≥21 vs 0-2) was associated with lower mortality risk ( RR=0.74, 95% CI: 0.64-0.85; P0.05). Subgroup analyses showed that being≥60 years old ( RR=0.82, 95% CI: 0.70-0.95), males ( RR=0.78, 95% CI: 0.64-0.95), females ( RR=0.79, 95% CI: 0.64-0.97), having a junior high school education or less ( RR=0.84, 95% CI: 0.71-0.99), and having a urban residence ( RR=0.77, 95% CI: 0.66-0.90) were all negatively associated with residents′ mortality risk (all P0.05). After adjusting for age, greater distance to the nearest sports facility ( RR=1.41, 95% CI: 1.08-1.83) and failing to meet the"10-minute fitness circle"criterion ( RR=1.25, 95% CI: 1.02-1.53) were associated with higher mortality risk among males (both P0.05). After adjusting for age and gender, urban residents with a greater distance to the nearest sports facility ( RR=1.29, 95% CI: 1.04-1.60) or not meeting the 10-minute fitness circle ( RR=1.18, 95% CI: 1.00-1.38) showed a significantly higher mortality risk (both P0.05). Conclusions:The ArcGIS analysis revealed that the distribution of sports facilities in China is characterized by a high proportion of large-scale facilities. Lower facility density within residential buffer zone and greater distance to the nearest facility increase mortality risk among adults.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

BACKGROUND: Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust. METHODS: Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method. RESULTS: Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased. CONCLUSIONS Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.
Rats ; Animals ; Alveolar Epithelial Cells/pathology* ; Dust ; Tin/adverse effects* ; Lung Neoplasms/pathology* ; Leptin/adverse effects* ; Receptors, Leptin ; China ; Signal Transduction ; Epithelial Cells/pathology* ; Mitogen-Activated Protein Kinase Kinases/adverse effects*

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
Area Under Curve ; Breast/diagnostic imaging* ; Breast Neoplasms/diagnostic imaging* ; China ; Deep Learning ; Humans ; ROC Curve ; Sensitivity and Specificity