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*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective:To explore the clinical efficacy of super-selective ophthalmic artery thrombolysis in the treatment of central retinal artery occlusion (CRAO).Methods:This is a retrospective case series study,based on the analysis of clinical data of 50 non-arteritic CRAO patients. The patients were advised to be treated with super-selective intra-ocular arterial thrombolysis at the Neurosurgery Department, Shenyang No. 4 People′s Hospital from May to December 2024, and treated with intra-arterial thrombolysis and postoperative management guidance by the Department of Neurosurgery, General Hospital of the Northern Theater Command. There were 36 males and 14 females, aged (59.5±10.2)years (range: 41 to 75 years). There were 5 cases of complete obstruction of the central retinal artery and 45 cases of subtotal obstruction.Before the operation, all patients underwent optical coherence tomography angiography (OCTA)+ocular vascular ultrasonography, and their visual acuity was measured using a standard visual acuity logarithmic scale, visual field was measured using the contrast visual field examination method;One week after the operation, all patients were rechecked for OCTA, visual acuity and visual field. The patients′ preoperative and postoperative visual field recovery status were compared. Significant effect was defined as an improvement of more than 3 lines of visual acuity or a complete improvement of visual field defects after treatment compared with pretreatment visual acuity; effectiveness was defined as an improvement of 1 to 2 lines of visual acuity or an improvement of visual field defects after treatment compared with pretreatment visual acuity.Results:The overall effective rate of 50 patients with CRAO treated with super-selective ophthalmic artery urokinase thrombolysis was 94.0% (47/50), with 29 very effective, 18 effective and 3 ineffective. The time from onset to surgery was 0 to 6 hours in 5 patients, with an effective rate of 5/5; >6 to 24 hours in 11 patients, with an effective rate of 10/11; >1 to 7 days in 21 patients, with an effective rate of 90.5%(19/21); >7 to 14 days in 9 patients, with an effective rate of 9/9; and >14 to 21 days in 4 patients, with an effective rate of 4/4, and the difference in effective rate between the different time windows of thrombolytic therapy was not statistically significant ( P=0.961). There were 3 cases of intraoperative and postoperative complications, including 1 case of ophthalmic artery entrapment, 1 case of femoral artery pseudoaneurysm and 1 case of fundus hemorrhage, but all of them were cured after symptomatic treatment. Conclusions:Intra-arterial thrombolysis for CRAO patients has a high effective rate and a low complication rate. The surgical time window can be extended to 21 days after the onset, which is of positive significance for the recovery and improvement of the patient′s final visual acuity.

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.

Objective:To explore the clinical efficacy of super-selective ophthalmic artery thrombolysis in the treatment of central retinal artery occlusion (CRAO).Methods:This is a retrospective case series study,based on the analysis of clinical data of 50 non-arteritic CRAO patients. The patients were advised to be treated with super-selective intra-ocular arterial thrombolysis at the Neurosurgery Department, Shenyang No. 4 People′s Hospital from May to December 2024, and treated with intra-arterial thrombolysis and postoperative management guidance by the Department of Neurosurgery, General Hospital of the Northern Theater Command. There were 36 males and 14 females, aged (59.5±10.2)years (range: 41 to 75 years). There were 5 cases of complete obstruction of the central retinal artery and 45 cases of subtotal obstruction.Before the operation, all patients underwent optical coherence tomography angiography (OCTA)+ocular vascular ultrasonography, and their visual acuity was measured using a standard visual acuity logarithmic scale, visual field was measured using the contrast visual field examination method;One week after the operation, all patients were rechecked for OCTA, visual acuity and visual field. The patients′ preoperative and postoperative visual field recovery status were compared. Significant effect was defined as an improvement of more than 3 lines of visual acuity or a complete improvement of visual field defects after treatment compared with pretreatment visual acuity; effectiveness was defined as an improvement of 1 to 2 lines of visual acuity or an improvement of visual field defects after treatment compared with pretreatment visual acuity.Results:The overall effective rate of 50 patients with CRAO treated with super-selective ophthalmic artery urokinase thrombolysis was 94.0% (47/50), with 29 very effective, 18 effective and 3 ineffective. The time from onset to surgery was 0 to 6 hours in 5 patients, with an effective rate of 5/5; >6 to 24 hours in 11 patients, with an effective rate of 10/11; >1 to 7 days in 21 patients, with an effective rate of 90.5%(19/21); >7 to 14 days in 9 patients, with an effective rate of 9/9; and >14 to 21 days in 4 patients, with an effective rate of 4/4, and the difference in effective rate between the different time windows of thrombolytic therapy was not statistically significant ( P=0.961). There were 3 cases of intraoperative and postoperative complications, including 1 case of ophthalmic artery entrapment, 1 case of femoral artery pseudoaneurysm and 1 case of fundus hemorrhage, but all of them were cured after symptomatic treatment. Conclusions:Intra-arterial thrombolysis for CRAO patients has a high effective rate and a low complication rate. The surgical time window can be extended to 21 days after the onset, which is of positive significance for the recovery and improvement of the patient′s final visual acuity.

Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances.Here,we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry(UPLC-MS/MS).This enabled simultaneous quantification of 1136 acyl-carnitines(C0-C26)within 10-min with good sensitivity(limit of detection＜0.7 fmol),linearity(cor-relation coefficient＞0.992),accuracy(relative error＜20％),precision(coefficient of variation(CV),CV＜15％),stability(CV＜15％),and inter-technician consistency(CV＜20％,n=6).We also established a quantitative structure-retention relationship(goodness of fit＞0.998)for predicting retention time(tR)of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters(tR,ion-pairs,and collision energy).Furthermore,we quantified 514 acylcarnitines in human plasma and urine,mouse kidney,liver,heart,lung,and muscle.This provides a rapid method for quantifying acyl-carnitines in multiple biological matrices.

Objective:To investigate the safety and clinical effect of testis-sparing microsurgery(TSMS)in the treatment of benign testis tumor(BTT).Methods:We retrospectively analyzed the clinical data on 16 cases of BTT treated in the Department of Andrology of the Affiliated Hospital of Qingdao University from October 2020 to February 2023.The median age of the patients was 23 years.All the tumors were unilateral,7 in the left and 9 in the right side,with a median diameter of 1.85 cm(1.0-3.5 cm).The patients all underwent color Doppler flow imaging(CDFI),MRI,semen analysis and examination of serum T,alpha-fetoprotein(AFP),human chorionic gonadotropin(HCG)and lactate dehydrogenase(LDH),followed by TSMS.The boundaries between the tumors and normal testis tissue were accurately identified under the microscope,and the tumors and the adjacent normal testis tissue 2 mm from their margins were excised completely.Bipolar coagulation forceps were used for wound hemostasis to maximally preserve the normal testis tissue.The resected specimens were subjected to fast frozen pathology intraoperatively,and the patients were followed up for 14-40 months by regular scrotal CDFI,MRI and examinations of serum T and semen parameters.Results:The levels of serum T,AFP,HCG and LDH and semen parameters were all within the normal range preoperatively.TSMS were successfully completed in all the cases,and all were pathologically confirmed as BTT according to the latest edition of WHO Classification of Tumors:Urinary and Male Genital Tumors.CDFI showed normal blood supply within the testis tissue at 1 month after surgery.No signs of intra-testicu-lar tumor residue,recurrence or metastasis,nor significant changes in the levels of serum T,AFP,HCG or LDH or semen parameters were observed during the follow-up as compared with the baseline.Natural conception was achieved in 2 cases at 16 and 18 months re-spectively after surgery.Conclusion:BTT can be differentially diagnosed by CDFI and MRI before surgery and confirmed by histo-pathology.TSMS can achieve complete excision of the tumor,maximal sparing of the normal testis tissue and thereby effective preserva-tion of male fertility.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.