Collagen-based materials, renowned for their biocompatibility and minimal immunogenicity, serve as exemplary substrates in a myriad of biomedical applications. Collagen-based micro/nanogels, in particular, are valued for their increased surface area, tunable degradation rates, and ability to facilitate targeted drug delivery, making them instrumental in advanced therapeutics and tissue engineering endeavors. Although extensive reviews on micro/nanogels exist, they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials. The current review offers an in-depth look into the manufacturing technologies, drug release mechanisms, and biomedical applications of collagen-based micro/nanogels to address this gap. First, we provide an overview of the synthetic strategies that allow the precise control of the size, shape, and mechanical strength of these collagen-based micro/nanogels by controlling the degree of cross-linking of the materials. These properties are crucial for their performance in biomedical applications. We then highlight the environmental responsiveness of these collagen-based micro/nanogels, particularly their sensitivity to enzymes and pH, which enables controlled drug release under various pathological conditions. The discussion then expands to include their applications in cancer therapy, antimicrobial treatments, bone tissue repair, and imaging diagnosis, emphasizing their versatility and potential in these critical areas. The challenges and future perspectives of collagen-based micro/nanogels in the field are discussed at the end of the review, with an emphasis on the translation to clinical practice. This comprehensive review serves as a valuable resource for researchers, clinicians, and scientists alike, providing insights into the current state and future directions of collagen-based micro/nanogel research and development.
Collagen/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Tissue Engineering/methods* ; Animals ; Biocompatible Materials/chemistry*

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Objective:To explore the predictive factors for ureteral stone impaction preoperatively and to construct a nomogram prediction model for impacted ureteral stones.Methods:A retrospective analysis was conducted on the clinical data of 209 patients with ureteral stones treated at The Second Affiliated Hospital of Zhengzhou University from July 2023 to June 2024. There were 164 males（78.5%）and 45 females（21.5%）. The age was 49（47，57）years，and the body mass index（BMI）was 25.10（23.55，27.24）kg/m2. Of the patients，85（40.7%）had comorbid hypertension and 85（40.7%）had comorbid diabetes. Stones were located on the left side in 124 patients（59.3%）and on the right side in 85 patients（40.7%）. Hydronephrosis was present in 169 patients（80.9%），and urine culture was positive in 29 patients（13.9%）. Patients were divided into impacted and non-impacted groups based on the presence or absence of ureteral stone impaction. Univariate and multivariate logistic regression analyses were performed to determine independent predictive factors for impacted ureteral stones. A nomogram model was constructed based on these results. The performance of the predictive model was evaluated using receiver operating characteristic（ROC）curves，calibration plots，and decision curve analysis（DCA）.Results:Among the 209 patients in this study，85（40.7%）experienced ureteral stone impaction. The impacted group had a significantly higher neutrophil-to-lymphocyte ratio（NLR）than the non-impacted group（3.91 ± 2.05 vs. 3.25 ± 2.10， P = 0.024），a higher rate of hydronephrosis［81.2%（69/85）vs. 80.6%（100/124）， P = 0.002］，larger stone surface area［（64.96 ± 39.96）mm2 vs.（51.86 ± 39.80）mm2， P = 0.021］，greater ureteral wall thickness（UWT）［（3.96 ± 1.37）mm vs.（3.06 ± 1.33）mm， P < 0.001］，and a higher ratio of the upper ureter diameter（D1）to the lower ureter diameter（D2）（DDR）（2.87 ± 1.58 vs. 2.00 ± 0.99， P < 0.001）. Univariate analysis showed that NLR，hydronephrosis，stone length，stone surface area，UWT，D1，D2，and DDR were statistically significant（ P < 0.05）. After multivariate logistic regression analysis，the following items were identified as independent predictors of impacted ureteral stones：NLR（ OR = 1.205，95% CI 1.026 - 1.415， P = 0.023），hydronephrosis（ OR = 1.840，95% CI 1.236 - 2.740， P = 0.003），stone length（ OR = 1.587，95% CI 1.142 - 2.206， P = 0.006），ureteral wall thickness（UWT）（ OR = 1.643，95% CI 1.263 - 2.136， P < 0.001），and DDR（ OR = 2.907，95% CI 1.040 - 8.130， P = 0.042）.Based on these independent predictive factors，a nomogram prediction model for impacted ureteral stones was constructed. The area under the ROC curve was 0.797（95% CI 0.737 - 0.858），and the calibration curve showed good consistency. The decision curve suggested that the model had good clinical net benefit. Conclusions:NLR，hydronephrosis，stone length，UWT，and DDR are all independent predictors for impacted ureteral stones. The nomogram model constructed based on these factors has good predictive performance.

Objective:To explore the independent factors influencing extraprostatic extension (EPE) after radical prostatectomy(RP) in patients with clinically localized prostate cancer by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. A nomogram model was developed and externally validated.Methods:Clinical and pathological data of 20 916 clinically localized prostate cancer patients (T 1-2N 0M 0) who underwent RP between 2010 and 2021 were extracted from the SEER database. The mean age was (61.71±7.09) years old, and a total of 17 835 patients (85.3%) were married.There were 2 243 patients (10.7%) with prostate-specific antigen (PSA) <4 ng/ml, 14 831 patients (70.9%) with ≥4 and <10 ng/ml, and 2 965 patients (14.2%) with ≥10 and <20 ng/ml. There were 14 870 patients (71.1%) with clinical staging of stage T 1, and 6 046 patients (28.9%) with T 2. There were 48 patients (0.2%) with pathological staging of stage T 1, 15 794 (75.5%) with T 2, 5 001(23.9%) with T 3, and 73 (0.3%) with T 4 stage after radical surgery.The patients of SEER database were divided into training and internal validation groups in a 7∶3 ratio by using stratified sampling. Additionally, data were collected for 75 clinically localized prostate cancer patients who underwent RP at the Second Affiliated Hospital of Zhengzhou University from September 2019 to September 2024, serving as the external validation group.The mean age was(65.39±7.45) years old. Among them, 73 (97.3%) were married. There were 2 patients (2.7%) with PSA <4 ng/ml, 17 patients (22.7%) with ≥4 and <10 ng/ml, and 34 patients (45.3%) with ≥10 and <20 ng/ml. There were 47 patients (62.7%) with clinical staging of stage T 1, and 28 patients (37.3%) with T 2. There were 7 patients (9.3%) with pathological staging of stage T 1, 48 patients (64.0%)with T 2, 18 patients (24.0%) with T 3, and 2 patients (2.7%) with T 4 stage after radical surgery. All patients were categorized into organ-confined (OC) and EPE groups based on post-surgical pathology. Univariate and multivariate logistic regression analyses, with a stepwise backward selection, were performed on the training group to identify independent risk factors of EPE, which were used to construct a nomogram model. Model performance was assessed using receiver operating characteristic (ROC) curve area under the curve (AUC), calibration curves, and decision curve analysis (DCA) for the training group, internal validation group, and external validation group. Results:EPE was observed in 3 585 cases (24.5%), 1 489 cases (23.8%), and 20 cases (26.7%) in the training, internal validation, and external validation groups, respectively. Logistic regression analyses identified preoperative age ( OR=1.026, P<0.001), PSA levels (≥10 and <20 ng/ml: OR=1.790, P<0.001; ≥20 ng/ml: OR=2.683, P<0.001), tumor maximum diameter (10-20 mm: OR=2.051, P<0.001; >20 mm: OR=3.937, P<0.001), biopsy Gleason score (score 7: OR=1.911, P<0.001; score 8: OR=2.906, P<0.001; score 9: OR = 5.278, P<0.001; score 10: OR=4.421, P=0.003), number of positive biopsy cores (≥4 cores: OR=1.260, P<0.001), and their proportion of total cores ( OR=1.012, P<0.001) as independent predictors of EPE. The nomogram model demonstrated good predictive performance, with AUC of 0.741, 0.748, and 0.724 in the training, internal validation, and external validation groups, respectively. Calibration and DCA curves confirmed the model’s excellent stability and generalizability. Conclusions:Age, PSA levels, maximum tumor diameter, biopsy Gleason score, number of positive biopsy cores, and their proportion of total cores are independent predictors of EPE after RP in clinically localized prostate cancer. The constructed model effectively predicts the risk of EPE occurrence.

Objective:To explore the independent factors influencing extraprostatic extension (EPE) after radical prostatectomy(RP) in patients with clinically localized prostate cancer by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. A nomogram model was developed and externally validated.Methods:Clinical and pathological data of 20 916 clinically localized prostate cancer patients (T 1-2N 0M 0) who underwent RP between 2010 and 2021 were extracted from the SEER database. The mean age was (61.71±7.09) years old, and a total of 17 835 patients (85.3%) were married.There were 2 243 patients (10.7%) with prostate-specific antigen (PSA) <4 ng/ml, 14 831 patients (70.9%) with ≥4 and <10 ng/ml, and 2 965 patients (14.2%) with ≥10 and <20 ng/ml. There were 14 870 patients (71.1%) with clinical staging of stage T 1, and 6 046 patients (28.9%) with T 2. There were 48 patients (0.2%) with pathological staging of stage T 1, 15 794 (75.5%) with T 2, 5 001(23.9%) with T 3, and 73 (0.3%) with T 4 stage after radical surgery.The patients of SEER database were divided into training and internal validation groups in a 7∶3 ratio by using stratified sampling. Additionally, data were collected for 75 clinically localized prostate cancer patients who underwent RP at the Second Affiliated Hospital of Zhengzhou University from September 2019 to September 2024, serving as the external validation group.The mean age was(65.39±7.45) years old. Among them, 73 (97.3%) were married. There were 2 patients (2.7%) with PSA <4 ng/ml, 17 patients (22.7%) with ≥4 and <10 ng/ml, and 34 patients (45.3%) with ≥10 and <20 ng/ml. There were 47 patients (62.7%) with clinical staging of stage T 1, and 28 patients (37.3%) with T 2. There were 7 patients (9.3%) with pathological staging of stage T 1, 48 patients (64.0%)with T 2, 18 patients (24.0%) with T 3, and 2 patients (2.7%) with T 4 stage after radical surgery. All patients were categorized into organ-confined (OC) and EPE groups based on post-surgical pathology. Univariate and multivariate logistic regression analyses, with a stepwise backward selection, were performed on the training group to identify independent risk factors of EPE, which were used to construct a nomogram model. Model performance was assessed using receiver operating characteristic (ROC) curve area under the curve (AUC), calibration curves, and decision curve analysis (DCA) for the training group, internal validation group, and external validation group. Results:EPE was observed in 3 585 cases (24.5%), 1 489 cases (23.8%), and 20 cases (26.7%) in the training, internal validation, and external validation groups, respectively. Logistic regression analyses identified preoperative age ( OR=1.026, P<0.001), PSA levels (≥10 and <20 ng/ml: OR=1.790, P<0.001; ≥20 ng/ml: OR=2.683, P<0.001), tumor maximum diameter (10-20 mm: OR=2.051, P<0.001; >20 mm: OR=3.937, P<0.001), biopsy Gleason score (score 7: OR=1.911, P<0.001; score 8: OR=2.906, P<0.001; score 9: OR = 5.278, P<0.001; score 10: OR=4.421, P=0.003), number of positive biopsy cores (≥4 cores: OR=1.260, P<0.001), and their proportion of total cores ( OR=1.012, P<0.001) as independent predictors of EPE. The nomogram model demonstrated good predictive performance, with AUC of 0.741, 0.748, and 0.724 in the training, internal validation, and external validation groups, respectively. Calibration and DCA curves confirmed the model’s excellent stability and generalizability. Conclusions:Age, PSA levels, maximum tumor diameter, biopsy Gleason score, number of positive biopsy cores, and their proportion of total cores are independent predictors of EPE after RP in clinically localized prostate cancer. The constructed model effectively predicts the risk of EPE occurrence.

Objective:To explore the predictive factors for ureteral stone impaction preoperatively and to construct a nomogram prediction model for impacted ureteral stones.Methods:A retrospective analysis was conducted on the clinical data of 209 patients with ureteral stones treated at The Second Affiliated Hospital of Zhengzhou University from July 2023 to June 2024. There were 164 males（78.5%）and 45 females（21.5%）. The age was 49（47，57）years，and the body mass index（BMI）was 25.10（23.55，27.24）kg/m2. Of the patients，85（40.7%）had comorbid hypertension and 85（40.7%）had comorbid diabetes. Stones were located on the left side in 124 patients（59.3%）and on the right side in 85 patients（40.7%）. Hydronephrosis was present in 169 patients（80.9%），and urine culture was positive in 29 patients（13.9%）. Patients were divided into impacted and non-impacted groups based on the presence or absence of ureteral stone impaction. Univariate and multivariate logistic regression analyses were performed to determine independent predictive factors for impacted ureteral stones. A nomogram model was constructed based on these results. The performance of the predictive model was evaluated using receiver operating characteristic（ROC）curves，calibration plots，and decision curve analysis（DCA）.Results:Among the 209 patients in this study，85（40.7%）experienced ureteral stone impaction. The impacted group had a significantly higher neutrophil-to-lymphocyte ratio（NLR）than the non-impacted group（3.91 ± 2.05 vs. 3.25 ± 2.10， P = 0.024），a higher rate of hydronephrosis［81.2%（69/85）vs. 80.6%（100/124）， P = 0.002］，larger stone surface area［（64.96 ± 39.96）mm2 vs.（51.86 ± 39.80）mm2， P = 0.021］，greater ureteral wall thickness（UWT）［（3.96 ± 1.37）mm vs.（3.06 ± 1.33）mm， P < 0.001］，and a higher ratio of the upper ureter diameter（D1）to the lower ureter diameter（D2）（DDR）（2.87 ± 1.58 vs. 2.00 ± 0.99， P < 0.001）. Univariate analysis showed that NLR，hydronephrosis，stone length，stone surface area，UWT，D1，D2，and DDR were statistically significant（ P < 0.05）. After multivariate logistic regression analysis，the following items were identified as independent predictors of impacted ureteral stones：NLR（ OR = 1.205，95% CI 1.026 - 1.415， P = 0.023），hydronephrosis（ OR = 1.840，95% CI 1.236 - 2.740， P = 0.003），stone length（ OR = 1.587，95% CI 1.142 - 2.206， P = 0.006），ureteral wall thickness（UWT）（ OR = 1.643，95% CI 1.263 - 2.136， P < 0.001），and DDR（ OR = 2.907，95% CI 1.040 - 8.130， P = 0.042）.Based on these independent predictive factors，a nomogram prediction model for impacted ureteral stones was constructed. The area under the ROC curve was 0.797（95% CI 0.737 - 0.858），and the calibration curve showed good consistency. The decision curve suggested that the model had good clinical net benefit. Conclusions:NLR，hydronephrosis，stone length，UWT，and DDR are all independent predictors for impacted ureteral stones. The nomogram model constructed based on these factors has good predictive performance.

Objective To analyze the characteristics of newly-diagnosed occupational diseases among female workers in Foshan City from 2013 to 2023. MethodsClinical data of newly-diagnosed occupational diseases among female workers in Foshan City from 2013 to 2023 were collected from the "Occupational Disease and Hazardous Detection Information System" subsystem of the "China Disease Prevention and Control Information System", and their distribution characteristics were analyzed using descriptive epidemiology. Results A total of 218 cases of newly-diagnosed occupational diseases among female workers in Foshan City were reported from 2013 to 2023, categorized into seven categories and 17 types. The median age and median length of exposure to occupational hazards among female workers were 45.1 and 7.8 years, respectively. The top three categories of newly-diagnosed cases were occupational diseases of the ear, nose, throat, and oral cavity (90 cases, all related to occupational noise-induced hearing loss), occupational chemical poisoning (61 cases), and occupational pneumoconiosis and other respiratory diseases (51 cases, including 50 cases with occupational pneumoconiosis). The newly-diagnosed cases were concentrated in Nanhai District, Shunde District, and Gaoming District, accounting for 75.2%. The newly-diagnosed cases were found in non-metallic mineral products manufacturing industry, metal products industry, and electrical machinery and equipment manufacturing industry, accounting for 50.9%. Enterprises of newly-diagnosed cases were mainly distributed in private enterprises and foreign-invested enterprises, accounting for 80.3%. The scale of enterprises of newly-diagnosed cases was mainly small- and medium-sized, accounting for 79.4%. Among the 218 cases, there were 21 cluster cases, involving 16 cases of occupational silicosis and five cases of occupational acute n-hexane poisoning, involving six manufacture industries, with 81.3% cases worked in sanitary ceramic products industry. Conclusion Occupational noise-induced deafness should be listed as a key occupational disease for female workers in Foshan City. Attention should be paid to the prevention of occupational diseases among middle-aged female workers in the non-metallic mineral products industry and small and medium-sized enterprises, and the cluster outbreaks of occupational pneumoconiosis.

BACKGROUND:The content of serum thrombin in patients with osteoarthritis is significantly higher than that in normal individuals,and thrombin can induce inflammatory degeneration of rat chondrocytes,suggesting that inhibiting the function of thrombin may become a method for treating osteoarthritis.Celecoxib is a common therapeutic drug for the clinical treatment of osteoarthritis.It is not yet known whether it improves chondrocyte degeneration by inhibiting the activity of thrombin. OBJECTIVE:To investigate the effect of celecoxib on thrombin-induced degeneration of rat chondrocytes. METHODS:Thrombin levels in the serum of osteoarthritis patients and normal individuals were detected by an ELISA kit.Primary chondrocytes of neonatal Sprague-Dawley rats were isolated,and all experiments were performed with cells from passage one.Chondrocytes were randomly divided into three groups:control group,thrombin group,and celecoxib group.The cell morphology of the three groups was observed under an inverted microscope,and an Edu kit was used to detect the cell proliferation.qRT-PCR was used to detect the expression of extracellular matrix components(aggrecan,elastin,cartilage oligomeric matrix proteins),inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),and chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6).The expression of type 2 collagen α1 was detected by immunofluorescence.Western blot method was used to detect the expression of catabolic metabolism genes,such as matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2. RESULTS AND CONCLUSION:Patients with osteoarthritis had higher levels of thrombin in the serum compared with normal individuals.Under the microscope,celecoxib was found to significantly inhibit fibroid changes in chondrocytes.Compared with the thrombin group,celecoxib inhibited the proliferation of chondrocytes.The downregulation of extracellular matrix gene expression,such as type II collagen α1,in the thrombin group was inhibited by celecoxib(P<0.05).Thrombin promoted the expression of inflammatory factors(interleukin-1,interleukin-6,and tumor necrosis factor-α),chemokines(monocyte chemotactic protein 2,monocyte chemotactic protein 7,granulocyte chemotactic protein 6),as well as catabolic genes(matrix metalloproteinase 9,matrix metalloproteinase 13,and cyclooxygenase 2),and under the intervention of celecoxib,the expression of these genes could be downregulated(P<0.05).Overall,these findings indicate that celecoxib inhibits the pro-inflammatory effects of thrombin and thereby ameliorates chondrocyte degeneration in rats.

Objective Screening for sensitive biomarkers for predicting and analyzing drug-induced renal toxicity,accelerates drug early development.Methods Focuses on epithelial cells of proximal convoluted tubules in human renal cortex(human kidney-2,HK-2)cells as the research object,screening for highly sensitive biomarkers using three nephrotoxic drugs(cisplatin,gentamicin,and aristolochic acid Ⅰ).Results The sensitivity of biomarkers in intracellular fluid is higher than in extracellular fluid,compared to detecting a single biomarker in the intracellular fluid.The combined detection of β2-microglobulin(β2-MG)and neutrophil gelatinase-associated lipocalin(NGAL)improved the accuracy of renal toxicity evaluation.Conclusion Based on the HK-2 cell model,the combined detection of β2-MG and NGAL in intracellular fluid can be used to predict renal toxicity in the drug's early development stage.

Objective To investigate the expression of miR-204 and silence information regulator 1(SIRT1)in colorectal cancer and their clinical value.Methods Cancer tissue specimens and paracancer tissue specimens of 60 patients with colorectal cancer treated in Department of Gastrointestinal Surgery of Affiliated Hospital of Jiaxing University from May 2018 to June 2020 were collected as study objects.Real time fluorogenic quantitative polymerase chain reaction was used to detect the gene expression of miR-204 and SIRT1,and the correlation between miR-204 and SIRT1 gene expression was compared by Pearson analysis.Immunohistochemical SABC method was used to detect SIRT1 protein expression,and relationship between different SIRT1 protein expression and clinicopathological features was compared.Kaplan-Meier method was used to analyze the survival difference of colorectal cancer patients with different SIRT1 protein expression.Results The mRNA expression of miR-204 gene in cancer tissues was significantly lower than that in paracancer tissues(P<0.05),and the mRNA expression of SIRT1 gene was significantly higher than that in paracancer tissues(P<0.05).Pearson correlation analysis showed that miR-204 was negatively correlated with SIRT1 mRNA expression in both paracancer tissues and cancer tissues(r=-0.647,-0.737,P<0.05).The expression of SIRT1 protein was correlated with the differentiation level,invasion level,lymph node metastasis and TNM stage of colorectal cancer(P<0.05),but not with patient age,gender,tumor size and tumor site(P>0.05).Kaplan-Meier analysis showed that the survival rate of patients with positive expression of SIRT1 in cancer tissues was significantly lower than that of patients with negative expression of SIRT1(χ2=5.001,P=0.025).Conclusion The expression of miR-204 is down-regulated and SIRT1 expression is up-regulated in colorectal cancer tissues,which may jointly promote the metastasis and invasion of colorectal cancer and affect the prognosis of patients through mutual influence.