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*

Objective To investigate the gene expression and regulatory mechanisms of mouse embryonic fibroblasts (MEFs) under inflammatory conditions, aiming to elucidate the role of MEFs in inflammatory responses and provide a foundation for discovering anti-inflammatory drugs that act by modulating MEF function. Methods MEFs cultured in vitro were divided into the following groups: lipopolysaccharides (LPS)-treated group, inflammatory conditioned medium (CM)-treated group, and control group, which were treated with LPS, CM, and equal volume solvent, respectively. Transcriptome sequencing was used to analyze the effects of two stimuli on gene expression profile of MEFs. Real time fluorescence quantitative PCR (RT-qPCR) was employed to verify the transcription levels of highly expressed genes of MEFs induced by CM. ELISA was performed to determine the concentrations of cytokines in cell supernatants. Finally, the regulatory effects of CM on the activation of signaling pathways in MEFs were analyzed by immunoblotting. Results Transcriptome analysis showed that both LPS and CM induced the transcription of a large number of genes in MEFs. Compared with LPS, CM potentiated the mRNA transcription of some acute phase proteins, inflammatory cytokines, chemokines, matrix metalloproteinases (MMP), prostaglandin synthetases, and colony-stimulating factors. The transcriptome analysis was verified by RT-qPCR. The results of ELISA showed that CM treatment significantly increased the secretion of interleukin 6 (IL-6), C-C motif chemokine ligand (CCL2), and C-X-C motif chemokine ligand (CXCL1) by MEFs compared with LPS. Mechanism study showed that both LPS and CM induced the phosphorylation of nuclear factor-κB p65 (NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), extracellular regulated protein kinases 1/2 (ERK1/2), and TANK-binding kinase (TBK) in MEFs, and CM strongly stimulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in MEFs. Conclusion Both LPS and CM can induce transcription and protein secretion of various inflammation-related genes in MEFs. CM can partly enhance LPS-induced activation of MEFs, and the mechanism may be related to the enhancement effect of CM on the activation STAT3 signaling pathway.
Animals ; Fibroblasts/immunology* ; Mice ; Lipopolysaccharides/pharmacology* ; Inflammation/metabolism* ; Signal Transduction/drug effects* ; Gene Expression Regulation/drug effects* ; Cytokines/genetics* ; Culture Media, Conditioned/pharmacology* ; Cells, Cultured

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 describe functional disability rate of anxiety disorders in Chinese community adults and explore related risk factors of functional disability.Methods:To conduct in-depth data analysis on China Mental Health Survey(CMHS).The diagnostic tool for anxiety disorders was the Composite International Diagnostic Inter-view-3.0,according to the Diagnostic and Statistical Manual for Mental Disorders,Fourth Edition(DSM-Ⅳ).The World Health Organization Disability Assessment Schedule,2nd edition,was the functional disability assessment standard for anxiety disorders.Weighted 12-month functional disability rate of DSM-Ⅳ anxiety disorder with co-morbidities and only anxiety disorder in population and those in patients,as well as days of partial disability were calculated.The effects of anxiety disorders comorbid other mental disorders and physical diseases and demographic factors on the severity and occurrence of functional disability were analyzed by multiple linear regression and logis-tic regression.Results:The functional disability rate of anxiety disorder with comorbidities in population was 1.7％,and 42.2％in patients,in which constituent rate of grade-four disability was the highest as 84.1％.The functional disability rate of only anxiety disorder in population was 0.3％,and 17.8％in patients.The medians of days of partial disability days in the past 30 days were from 0 to 14.42.Multiple linear regression showed a positive association between comorbid anxiety disorder with other mental disorders and physical diseases(β=0.24),comor-bid other mental disorders and physical diseases(β=0.21),physical diseases(β=0.18),comorbid anxiety disor-der and physical diseases(β=0.15),comorbid anxiety disorder with other mental disorders(β=0.08),other men-tal disorders(β=0.07),only anxiety disorder(β=0.06),lower education level(β=0.12),lower economic status(β=0.08),older age(β=0.06),non-marital status(β=0.06),male(β=0.02)and the severity of functional dis-ability.Logistic regression showed that comorbid anxiety with other mental disorders and physical diseases(OR=64.07),comorbid anxiety disorders with other mental disorders(OR=36.75),comorbid other mental disorders with physical diseases(OR=20.60),comorbid anxiety with physical diseases(OR=18.88),anxiety disorder(OR=9.20),other mental disorders(OR=6.65),physical diseases(OR=4.00),65 years old and over(OR=4.40),50 to 64 years old(OR=2.33),low economic status(OR=2.10),illiterate and below primary school educational level(OR=1.89),middle economic status(OR=1.70),elementary school educational level(OR=1.59),non-marital status(OR=1.47),male(OR=1.16)were the risk factors of the occurrence of functional disability.Conclusion:Comorbidity of anxiety disorders and other mental disorders,and physical diseases increases severity and occurrence of functional disability.Comorbidity,male,gender,older age,lower economic and educa-tional level and non-marital are risk factors of anxiety disorder functional disability.

Objective:To describe disability rates of dementia in community residents aged 65 years and over in China,and explore related risk factors of disability.Methods:This study conducted an in-depth data analysis of the China Mental Health Survey.World Health Organization Disability Assessment Schedule 2.0(WHODAS 2.0)was used to assess dementia disability,Community Screening Interview for Dementia(CSID)and Geriatric Mental Status Examination(GMS)were used for dementia screening and diagnosing.Univariate analysis was used to calcu-late the weighted disability rates of dementia in population and in patients,and their population distribution.Multiple linear regression and logistic regression were used to analyze the risk factors of the occurrence of dementia disability and its severity.Results:The weighted disability rate of dementia was 2.1％in population,and 38.6％in pa-tients.The disability rates of comorbid dementia in population and in patients were higher than those of patients with only dementia.Female,older age,lower education level,lower economic status,and lower cognitive test scores in CSID had higher disability rates of dementia in population.Female and urban resident had higher disability rates of dementia in patients.Multiple linear regression showed economic status(β=0.11),gender(β=0.11),age(β=0.10),and treatment in the last 12 months(β=-0.20)were statistically associated with WHODAS 2.0 scores.Multiple logistic regression showed female(OR=2.81)and treatment in the last 12 months(OR=2.38)were statistically associated with disability.Conclusions:Persons with low economic status,female and elderly peo-ple are the high-risk groups for dementia disability.It should be paid attention to prevent dementia and its conse-quential disabilities.

Objective To observe the interventional effects of complex probiotic powder on blood bio-chemical indices and vaginal flora in pregnant women with high risk of gestational diabetes mellitus(GDM). Methods One hundred and ten pregnant women with high risk of GDM recruited from the outpatient clinics of the obstetric department and nutrition department in this hospital were randomly divided into the probiotic intervention group (n=55) and the placebo control group (n=55).The intervention group was given 1 bag of complex probiotic powder per day,and the control group was given 1 bag of placebo powder.The colors,shapes,sizes and tastes of powders in the two groups remained the consistency.The intervention duration in this trial was 23 weeks.The questionnaire survey were conducted at baseline and at the intervention endpoint,and the blood biochemical indexes detections were performed at baseline,after 24-28 weeks of gestation,and after 34-38 weeks of gestation,respectively.In addition,the differences in the composition of the vaginal flora structure between the two groups of high risk pregnant women with GDM were detected at the intervention endpoint.Results A total of 97 cases were eventually included in the statistical analysis.Among them,there were 50 cases in the probiotic intervention group and 47 cases in the placebo control group.At the end of the 23 week intervention,there were no statistically significant differences in fasting blood glucose,red blood cells,hemoglobin,leukocytes,ferritin,total protein,albumin,glutamic transaminase,glutamic oxalate transam-inase and total bilirubin between the probiotic intervention group and placebo control group (P>0.05).In terms of vaginal flora,there was a significant difference in some indicators of α diversity between the probiotic group and placebo control group (P<0.05),and there was no significant difference in β diversity between the two groups (P>0.05).At the level of vaginal flora phyla,there were significant differences in the Firmicutes,Actinobacteria,Desulfobacterota,Deferribacterota,and δ-Myxococcota between the two groups (P<0.05).At the level of vaginal flora genera,the relative abundance of Lactobacillus spp.in the probiotic intervention group was significantly higher than that in the control group (P<0.05).Conclusion Complex probiotic pow-der supplementation may have a limited role in improving blood glucose and other related biochemical indica-tors in high-risk pregnant women with GDM.But it has a certain role in regulating the vaginal micro ecological balance in pregnant women with high risk of GDM.

Objective:To evaluate the clinical value of cognitive and motor function in predicting conversion to neurodegenerative disorders in patients with isolated rapid eye movement sleep behavior disorder (iRBD).Methods:Forty-seven patients with iRBD were collected from the Department of Neurology of Tianjin Medical University General Hospital and Tianjin Medical University General Hospital Airport Site during October 2018 and June 2022. All participants received comprehensive evaluations of cognitive and motor function at baseline. The visuospatial function was evaluated by Rey-Osterrieth Complex Figure Test (ROCF)-copy, the memory function was evaluated by Auditory Verbal Learning Test and ROCF-recall, the attention-executive function was evaluated by Trail Making Test (TMT) and Stroop Color-Word Test, and the language function was evaluated by Boston Naming Test. The motor function was evaluated by Unified Parkinson′s Disease Rating Scale-Ⅲ, Alternate-tap Test (ATT), and 3-meter Timed Up and Go Test. The iRBD patients with phenoconversion were identified during follow-up. Receiver operating characteristic curve and generalized linear model Logistic regression were applied to identify the optimal combination of cognitive and motor tests in distinguishing the converters from non-converters in patients with iRBD. Multivariate Cox regression analyses were applied to evaluate the independent risk factors in predicting conversion to neurodegenerative diseases in patients with iRBD.Results:The median follow-up duration was 3 years. Forty-five iRBD patients were included in the analysis eventually, as 2 dropped out at follow-up. Twenty-one iRBD patients developed neurodegenerative disorders, with 14 presenting motor phenotype and 7 cognitive phenotype. Baseline ROCF-copy, TMT-A and ATT were best combination in identifying iRBD patients with phenoconversion [sensitivity: 90.0%, specificity: 87.5%, area under curve (AUC): 0.931, P<0.001]. Baseline TMT-A and ATT were best combination in identifying iRBD patients with motor phenotype conversion (sensitivity: 100.0%, specificity: 66.7%, AUC: 0.872, P<0.001); Baseline TMT-A performed best in identifying iRBD patients with cognitive phenotype conversion (sensitivity: 83.3%, specificity: 91.7%, AUC: 0.917, P<0.001). Multivariate Cox regression analysis showed that individuals with poorer performance of TMT-A (cut-off value: 63.0 s) and ATT (cut-off value: 205.5 taps/min) than the cut-off values at baseline had higher risks for developing to neurodegenerative disorders, with HR values of 5.455 (95% CI 1.243-23.941, P=0.025) and 11.279 (95% CI 1.485-85.646, P=0.019), respectively. Conclusions:In iRBD, ROCF-copy, TMT-A and ATT served as optimum combination in predicting phenoconversion, whereas TMT-A and ATT served as optimum combination in predicting motor phenotype, and TMT-A performed best in predicting cognitive phenotype. The performance in TMT-A and ATT in iRBD could predict the risk of developing to neurodegenerative disorders independently.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective To observe the adverse reactions of different anesthesia methods used in bronchoscopic diagnosis and treatment,and provide ideas for clinical selection of the best anesthesia methods.Methods 150 patients from June 2022 to June 2023 for bronchoscope were randomly divided into group W(atomization with lidocaine combined with intravenous sedation),group Q(laryngeal mask general anesthesia)and group H(lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia),with 50 cases in each group.Heart rate(HR),mean arterial pressure(MAP)and percutaneous arterial oxygen saturation(SpO2)values were recorded at different time points,adverse reactions during recovery,recovery time and dosage of anesthetic drugs were recorded.Results At T1 and T2,SpO2 in group W(89.4±0.7)%and(91.8±0.3)%were lower than that(99.6±0.8)%in T0,and lower than those(98.6±1.3)%and(98.5±1.6)%in group Q and(99.7±0.3)%and(98.4±1.6)%in group H,the difference were statistically significant(P<0.05).At T1 and T2,the MAP of group W were(108.5±7.8)and(105.6±7.3)mmHg,which were significantly higher than those of T0(87.5±8.6)mmHg,and higher than those of group Q(92.6±8.5)and(85.8±11.3)mmHg,respectively,higher than those(85.7±9.2)and(85.2±10.8)mmHg in group H,the differences were statistically significant(P<0.05).The MAP of group Q at T1 and T3 was(92.6±8.5)and(91.4±8.6)mmHg,respectively,higher than that of T0(87.8±7.5)mmHg,and higher than those of group H(85.7±9.2)and(86.5±7.2)mmHg,with statistical significance(P<0.05).At T1 and T2,the HR of group W was(92.7±9.6)and(91.3±9.2)times/min,higher than that of T0(72.3±8.4)times/min,and higher than those of group Q(75.3±11.6)and(78.5±12.8)times/min,respectively,and higher than those of group H(76.6±10.7)and(77.2±8.5)times/min,and the differences were statistically significant(P<0.05).The hypoxemia,arrhythmia and cough rates in group Q were higher than those in group W and group H,and the differences were statistically significant(P<0.05).The recovery time of group H was(11.5±7.2)min,which was significantly lower than that of group W(16.8±8.5)min and group Q(17.6±6.4)min,and the differences were statistically significant(P<0.05).The dosage of propofol in group H was(314.3±12.7)mg and remifentanil was(211.6±12.5)μg,both lower than those in group W(390.5±12.4)mg and(268.4±13.6)μg,and lower than those in group Q(387.6±15.2)mg and(372.5±15.3)μg.The differences were statistically significant(P<0.05).The dosage of micuronium chloride was(23.7±3.8)mg in group H,lower than(32.5±4.3)mg in group Q,and the difference was statistically significant(P<0.05).Conclusion Lidocaine sprayed by laryngeal anesthetic tube combined with general anesthesia is the best anesthesia method for bronchoscopic diagnosis and treatment,which is beneficial to respiratory management and less adverse reactions in perioperative period.