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*

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Objective:To study the predictive value of peripheral blood cathepsin (Cat) level on arteriovenous fistula stenosis and therapeutic effect of urokinase combined with argatroban in patients with maintenance hemodialysis (MHD).Methods:The clinical data of 120 patients with MHD from January 2017 to January 2021 in the First Affiliated Hospital of Hebei North University were retrospectively analyzed. Among them, 72 patients had arteriovenous fistula stenosis (stenosis group), and 48 patients had not arteriovenous fistula stenosis (non-stenosis group). The patients in stenosis group were treated with urokinase combined with argatroban, and the therapeutic effect was evaluated; the stenosis degree of arteriovenous fistula stenosis was evaluated by digital subtraction angiography (DSA). The levels of Cat K and S in peripheral blood were detected by enzyme linked immunosorbent assay. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of Cat K and S in peripheral blood on arteriovenous fistula stenosis in patients with MHD. The independent risk factor of arteriovenous fistula stenosis in patients with MHD was analyzed by multivariate Logistic regression analysis.Results:The levels of Cat K and S in peripheral blood in stenosis group were significantly higher than those in non-stenosis group: (404.34 ± 12.43) μg/L vs. (344.22 ± 12.09) μg/L and (124.55 ± 13.43) μg/L vs. (84.60 ± 12.45) μg/L, and there were statistical differences ( t = 26.39 and 16.68, P<0.01). The result of DSA showed that mild stenosis of arteriovenous fistula stenosis was in 33 cases, moderate stenosis in 23 cases, and severe stenosis in 16 cases. The levels of Cat K and S in peripheral blood in patients with moderate stenosis and severe stenosis were significantly higher than those in patients with mild stenosis: (399.83 ± 11.79) and (476.27 ± 12.24) μg/L vs. (372.61 ± 12.88) μg/L, (125.77 ± 12.75) and (151.69 ± 11.86) μg/L vs. (110.54 ± 12.07) μg/L, the indexes in patients with severe stenosis were significantly higher than those in patients with moderate stenosis, and there were statistical differences ( P<0.01). After treatment, excellent was in 40 cases, effective in 23 cases, and ineffective in 9 cases. The levels of Cat K and S in peripheral blood in patients with effective and ineffective were significantly higher than those in patients with excellent: (404.78 ± 10.96) and (491.30 ± 10.26) μg/L vs. (384.52 ± 10.36) μg/L, (121.85 ± 10.99) and (232.65 ± 10.61) μg/L vs. (101.78 ± 10.61) μg/L, the indexes in patients with ineffective were significantly higher than those in patients with effective, and there were statistical differences ( P<0.01). The ROC curve analysis result showed that the area under the curve of Cat K combined with Cat S in peripheral blood in forecasting arteriovenous fistula stenosis in patients with MHD was larger than that of Cat K and S alone (0.699 vs. 0.635 and 0.611), and the accuracy and specificity were also significantly higher (80.83% vs. 48.33% and 60.00%, 89.58% vs. 76.25% and 81.33%), the optimum cut-off values of Cat K and S in peripheral blood were 401.23 and 123.65 μg/L. Multivariate Logistic regression analysis result showed that the levels of Cat K and S in peripheral blood were the independent risk factor of arteriovenous fistula stenosis in patients with MHD ( OR = 1.02 and 1.63, 95% CI 0.90 to 1.93 and 1.33 to 2.32, P<0.01). Conclusions:The levels of Cat K and S in peripheral blood can predict the occurrence and extent of arteriovenous fistula stenosis in patients with MHD, and could also predict the therapeutic effect of urokinase combined with agatroban.

OBJECTIVE: To assess the diagnostic value of copy number variation sequencing (CNV-seq) in the genetic etiology of fetuses with nasal bone dysplasia (NBD). METHODS: A total of 217 fetuses discovered with NBD from December 2017 to December 2020 were divided into the isolated NBD group and NBD combined with other anomalies group, for which copy number variations (CNVs) were analyzed. RESULTS: A total of 40 fetal abnormalities were detected in 217 cases, with an overall abnormal rate of 18.4%. These included 31 cases with aneuploidies (14.3%, 31/217) and 9 cases with genomic CNVs (4.1%, 9/217). Five cases of trisomy 21 (3.5%, 5/144) and two CNVs cases with unknown clinical significance (1.4%, 2/144) were detected in the isolated group. As for the combined NBD group, 26 aneuploidies (35.6%, 26/73), including 19 cases with trisomy 21, 6 cases with trisomy 18, 1 case with trisomy 13, 5 cases with pathogenic CNVs (6.8%, 5/73), and 2 cases with CNVs of unknown clinical significance (2.7%, 2/73) were detected. A significant difference was detected between the two groups (P < 0.01). CONCLUSION The detection rate of CNV-seq is high for chromosomal aneuploidies and pathogenic CNVs in fetuses with NBD, particularly in those combined with other ultrasonic abnormalities.
Aneuploidy ; Bone Diseases, Developmental ; Chromosome Aberrations ; DNA Copy Number Variations ; Down Syndrome/genetics* ; Female ; Fetus/abnormalities* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy

Objective : To compare the accuracies of implants with dynamic real-time navigation versus digital guide navigation to provide a reference for clinical precision dental implants. Methods: Forty-six cases (seventy teeth) with missing teeth admitted to the Department of Stomatology, Wuzhou Red Cross Hospital from April 2018 to December 2019 were randomly divided into two groups (thirty-five teeth in each group) for dynamic real-time navigation and digital guide navigation implantation techniques. To compare the entry point, apex point, depth and angle deviation of the preoperative and postoperative position of implants in the two groups. SPSS 21.0 software was used for statistical analysis. Results : Dental implants were successfully placed in both groups. The deviations of apex point, depth and angle in the dynamic real-time navigation group were all smaller than those in the digital guide navigation group, and the differences were statistically significant (P < 0.05). There was no statistically significant deviation in the entry point between the two groups (P > 0.05). Conclusion In this study, both techniques had good clinical effects. The accuracy of dynamic real-time navigation was higher than that of digital guidance.

Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype-phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.
Humans ; Phenotype ; Wnt Proteins

Objective: This study analyzed the active surveillance data of foodborne diseases among primary and secondary school students in Maanshan City. The purpose is to explore its epidemiological characteristics and provide evidence for effective prevention and control measures. Methods: Descriptive epidemiological method was used to analyze 976 cases of primary and secondary school students collected at the sentinel hospital in Maanshan City. Chi-square test was used to compare the distribution of foodborne diseases among primary and secondary school students with different characteristics, and the Logistic regression analysis was conducted on the influencing factors timely rate of health-seeking. Results: There were statistically significant differences in the distribution of food-borne diseases among primary and secondary school students in gender, urban and rural areas, hospital grades, administrative areas, eating places and food packaging or processing methods ( χ 2=5.24, 6.86, 41.45, 48.09, 27.87, 23.62, P < 0.05 ). There were 624 males (66.78%) and 352 females (33.22%). July-October was the peak period of health-seeking ( 45.77 %), and Huashan District (31.45%) had the largest number of cases. Multivariate Logistic regression showed that women ( OR =1.36, 95% CI =1.04-1.79), summer ( OR =1.68, 95% CI =1.19-2.35), autumn ( OR =1.49, 95% CI =1.04-2.12) and the Hexian area ( OR =2.71, 95% CI =1.77-4.15) were positively correlated with the timeliness of health-seeking. Conclusion The cases of foodborne diseases in primary and secondary schools in Maanshan City were mainly male. Summer and autumn were the main onset times. Huashan District was the key prevention county. It is suggested that all departments should take active and effective measures to strengthen the prevention and control of foodborne diseases among primary and secondary school students.

The low-resolution ultrasound images have poor visual effects. Herein we propose a method for generating clearer intravascular ultrasound images based on super-resolution reconstruction combined with generative adversarial networks. We used the generative adversarial networks to generate the images by a generator and to estimate the authenticity of the images by a discriminator. Specifically, the low-resolution image was passed through the sub-pixel convolution layer -feature channels to generate -feature maps in the same size, followed by realignment of the corresponding pixels in each feature map into × sub-blocks, which corresponded to the sub-block in a high-resolution image; after amplification, an image with a -time resolution was generated. The generative adversarial networks can obtain a clearer image through continuous optimization. We compared the method (SRGAN) with other methods including Bicubic, super-resolution convolutional network (SRCNN) and efficient sub-pixel convolutional network (ESPCN), and the proposed method resulted in obvious improvements in the peak signal-to-noise ratio (PSNR) by 2.369 dB and in structural similarity index by 1.79% to enhance the diagnostic visual effects of intravascular ultrasound images.
Blood Vessels ; diagnostic imaging ; Endosonography ; methods ; Image Enhancement ; methods ; Image Processing, Computer-Assisted ; methods ; Signal-To-Noise Ratio

Objective To compare the characteristics of the tremor of multiple system atrophy Parkinsonism type (MSA-P) with Parkinson's disease (PD), and improvement after acute levodopa challenge test. Methods From Match to September 2017, 70 patients with PD and 23 patients with probable MSA-P were included. All the patients were required of rest or postural tremor in at least one extremity or head, and accepted acute levodopa challenge test and analysis for dominant tremor frequency, amplitude and rhythm under resting state, posturing and holding 1000 g state, respectively.Results The score of Unified Parkinson Diease Rating Scale Part III was higher in MSA-P patients than in PD patients (t=-2.098, P<0.05), with less improvement after acute levodopa challenge test (Z=-9.446, P<0.01), while the tremor score and improvement were not significantly different between two groups (P>0.05). There were more frequence with non-alternating or synchronic tremor rhythm (χ2=8.756, P<0.01) and small irregular tremor in rest tremor (χ2=4.788, P<0.05) in MSA-P patients than in PD patients, as well as the high frequency tremor (>6 Hz) in postural tremor (χ2=11.312, P<0.01). The frequency of rest tremor was higher in MSA-P patients than in PD patients (t=-2.119, P<0.05), as well as the frequency of postural tremor with 1000 g (t=-2.274, P<0.05). Both PD and MSA-P patients showed, the lower frequency the postural tremor was, the higher the tremor scores were. There were 25% PD patients with head tremor, while none in MSA-P patients. Tremor score improved more than 30% after acute levodopa challenge test in 22.7% MSA-P patients, but none improved in UPDRS score. The frequence of tremor score improvement was more in female MSA-P patients than in males (P<0.05).Conclusion The features of the tremor are similar in PD and MSA-P, with some differences that MSA-P tend to higher frequency in rest or postural tremor, more non-alternating or synchronic tremor rhythm in rest tremor, and fewer has tremor besides limbs. Some MSA-P patients improve after acute levodopa challenge test, and women may improve more than men.