Animal experiments are widely used in biomedical research for safety assessment, toxicological analysis, efficacy evaluation, and mechanism exploration. In recent years, the ethical review system has become more stringent, and awareness of animal welfare has continuously increased. To promote more efficient and cost-effective drug research and development, the United States passed the Food and Drug Administration (FDA) Modernization Act 2.0 in September 2022, which removed the federal mandate requiring animal testing in preclinical drug research. In April 2025, the FDA further proposed to adopt a series of "new alternative methods" in the research and development of drugs such as monoclonal antibodies, which included artificial intelligence computing models, organoid toxicity tests, and 3D micro-physiological systems, thereby gradually phasing out traditional animal experiment models. Among these cutting-edge technologies, 3D bioprinting models are a significant alternative and complement to animal models, owing to their high biomimetic properties, reproducibility, and scalability. This review provides a comprehensive overview of advancements and applications of 3D bioprinting technology in the fields of biomedical and pharmaceutical research. It starts by detailing the essential elements of 3D bioprinting, including the selection and functional design of biomaterials, along with an explanation of the principles and characteristics of various printing strategies, highlighting the advantages in constructing complex multicellular spatial structures, regulating microenvironments, and guiding cell fate. It then discusses the typical applications of 3D bioprinting in drug research and development,including high-throughput screening of drug efficacy by constructing disease models such as tumors, infectious diseases, and rare diseases, as well as conducting drug toxicology research by building organ-specific models such as those of liver and heart. Additionally,the review examines the role of 3D bioprinting in tissue engineering, discussing its contributions to the construction of functional tissues such as bone, cartilage, skin, and blood vessels, as well as the latest progress in regeneration and replacement. Furthermore, this review analyzes the complementary advantages of 3D bioprinting models and animal models in the research of disease progression, drug mechanisms, precision medicine, drug development, and tissue regeneration, and discusses the potential and challenges of their integration in improving model accuracy and physiological relevance. In conclusion, as a cutting-edge in vitro modeling and manufacturing technology, 3D bioprinting is gradually establishing a comprehensive application system covering disease modeling, drug screening, toxicity prediction, and tissue regeneration.

Animal experiments are widely used in biomedical research for safety assessment, toxicological analysis, efficacy evaluation, and mechanism exploration. In recent years, the ethical review system has become more stringent, and awareness of animal welfare has continuously increased. To promote more efficient and cost-effective drug research and development, the United States passed the Food and Drug Administration (FDA) Modernization Act 2.0 in September 2022, which removed the federal mandate requiring animal testing in preclinical drug research. In April 2025, the FDA further proposed to adopt a series of "new alternative methods" in the research and development of drugs such as monoclonal antibodies, which included artificial intelligence computing models, organoid toxicity tests, and 3D micro-physiological systems, thereby gradually phasing out traditional animal experiment models. Among these cutting-edge technologies, 3D bioprinting models are a significant alternative and complement to animal models, owing to their high biomimetic properties, reproducibility, and scalability. This review provides a comprehensive overview of advancements and applications of 3D bioprinting technology in the fields of biomedical and pharmaceutical research. It starts by detailing the essential elements of 3D bioprinting, including the selection and functional design of biomaterials, along with an explanation of the principles and characteristics of various printing strategies, highlighting the advantages in constructing complex multicellular spatial structures, regulating microenvironments, and guiding cell fate. It then discusses the typical applications of 3D bioprinting in drug research and development,including high-throughput screening of drug efficacy by constructing disease models such as tumors, infectious diseases, and rare diseases, as well as conducting drug toxicology research by building organ-specific models such as those of liver and heart. Additionally,the review examines the role of 3D bioprinting in tissue engineering, discussing its contributions to the construction of functional tissues such as bone, cartilage, skin, and blood vessels, as well as the latest progress in regeneration and replacement. Furthermore, this review analyzes the complementary advantages of 3D bioprinting models and animal models in the research of disease progression, drug mechanisms, precision medicine, drug development, and tissue regeneration, and discusses the potential and challenges of their integration in improving model accuracy and physiological relevance. In conclusion, as a cutting-edge in vitro modeling and manufacturing technology, 3D bioprinting is gradually establishing a comprehensive application system covering disease modeling, drug screening, toxicity prediction, and tissue regeneration.

Objective: To analyze the epidemiological characteristics and trends of other infectious diarrhea among children under 18 years old in Guangzhou City from 2014 to 2020, and to explore the correlation between climatic factors and the incidence of the disease, so as to provide reference for the early prevention of infectious diseases. Methods: The data of cases of other infectious diarrhea and meteorological data of children under 18 years old in Guangzhou City from 2014 to 2020 were collected through the Chinese Infectious Disease Reporting System and the Guangzhou Meteorological Bureau. The correlation between meteorological factors and the incidence of other infectious diarrhea was analyzed using negative binomial regression. Results: A total of 104 566 cases of other infectious diarrhea among children under 18 years old were reported in Guangzhou City from 2014 to 2020, with a male to female ratio of 1.48∶1. The incidence rate was the highest in 2017 (980.83 per 100 000) and the lowest in 2020 (388.22 per 100 000). The peak of incidence occurred from October to March of the following year. Children under 5 years old accounted for 87.95% of all cases. The number of cases of other infectious diarrhea was negatively correlated with the temperature of the previous 6 days ( IRR = -0.07 ), and positively correlated with the temperature difference on the day of onset ( IRR =0.02) (both P <0.05). It was also positively correlated with the wind speed of the previous 7 days ( IRR=0.07, P <0.05), but there was no statistically significant correlation with the relative humidity on the day of onset ( IRR=-0.00, P >0.05). Conclusions Low temperature, large temperature difference, and high wind speed can increase the risk of other infectious diarrhea. It is necessary to strengthen the prediction and early warning in conjunction with meteorological changes, and warn kindergartens and schools to enhance preventive measures against the clustering of other infectious diarrhea cases.

Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

BACKGROUND:Circular RNAs(circRNAs)play important roles in a variety of diseases or tumors,and recent findings have revealed that circRNAs are abnormally expressed in knee osteoarthritis and are involved in disease progression through microRNA/mRNA regulation. OBJECTIVE:To investigate the effect of circRNA WD repeat containing protein 1(circ-BRWD1)/miR-488-3p/DNA methyltransferase 3A(DNMT3A)on the proliferation and apoptosis of chondrocytes in knee osteoarthritis. METHODS:Real-time fluorescence quantitative PCR was performed to detect the expression of circ-BRWD1,miR-488-3p,DNMT3A in knee osteoarthritis chondrocytes.Cells were divided into si-NC group,si-circ-BRWD1 group,vector group,circ-BRWD1 group,si-circ-BRWD1+anti-miR-NC group,si-circ-BRWD1+anti-miR-488-3p group,miR-NC group,miR-488-3p group,anti-miR-NC group,anti-miR-488-3p group,miR-488-3p+vector group,miR 488-3p+DNMT3A group.Real-time fluorescence quantitative PCR was used to detect circ-BRWD1,miR-488-3p,DNMT3A expression,MTT and flow cytometry assay were used to detect cell proliferation and apoptosis.Western blot assay was used to detect DNMT3A and proliferation/apoptosis-related protein expression.Dual luciferase reporter assay was used to Dual luciferase reporter assay to detect the targeting relationship of circ-BRWD1 with miR-488-3p and miR-488-3p with DNMT3A. RESULTS AND CONCLUSION:circ-BRWD1 and DNMT3A were highly expressed and miR-488-3p was lowly expressed in knee osteoarthritis chondrocytes compared with normal chondrocytes.Knockdown of circ-BRWD1 or overexpression of miR-488-3p inhibited proliferation and induced apoptosis in knee osteoarthritis chondrocytes.circ-BRWD1 targeted negative regulation of miR-488-3p and inhibition of miR-488-3p reversed the effect of circ-BRWD1 knockdown on chondrocyte proliferation and apoptosis in knee osteoarthritis.miR-488-3p targeted negative regulation of DNMT3A and upregulation of DNMT3A reversed the effect of miR-488-3p overexpression on chondrocyte proliferation and apoptosis in knee osteoarthritis.circ-BRWD1 could regulate the expression of DNMT3A by regulating miR-488-3p.To conclude,knockdown of circ-BRWD1 inhibits chondrocyte proliferation and induces apoptosis in knee osteoarthritis,and the mechanism of action may be related to the regulation of miR-488-3p/DNMT3A axis.

Objective To present the initial practice of a novel procedure for the surgical treatment of inguinal hernia-"lateral approach single-incision laparoscopic totally extraperitoneal(L-SILTEP)repair"in certain specific situations.Methods The clinical data of 110 inguinal hernia patients who underwent L-SILTEP in the First Affiliated Hospital of Ningbo University,Shanghai General Hospital affiliated to Shanghai Jiao Tong University School of Medicine,and Shanghai East Hospital affiliated to Tongji University from June 2021 to March 2024 were collected retrospectively.Patients' demographics,surgical details,length of hospital stay,and postoperative outcomes were analyzed respectively.Results All surgeries were completed successfully and there was no conversion.The median surgical time was 55(41.25,70)mins and the intraoperative blood loss was 5(2,10)mL.In surgery,inferior epigastric artery injury occurred in 5 cases(4.5%)and spermatic cord injury occurred in 1 case(0.9%).The mean visual analog scale(VAS)scores pain assessment at 6,24,and 48 h after surgery were 3.0±0.8,1.9±0.7 and 1.1±0.4,respectively.The duration of hospital stay was(3.3±0.7)days.The most common postoperative complication was seroma,which occurred in 9 cases(8.2%).Additionally,extraperitoneal hematoma occurred in 1 case(0.9%)and scrotum effusion in 1 case(0.9%).Conclusions Generally,L-SILTEP is safe,feasible and effective.However,due to its advanced technique-demand,the application of L-SILTEP should be patient-specific and surgeon-specific.The successful implementation of this surgical procedure necessitates extensive training and meticulous attention to the surgical details.

Intraspinal air is a rare complication of intraspinal anesthesia.Reported cases of intraspinal or intracranial air are mostly associated with the air insufflation resistance test,while those associated with the normal saline resistance test are rare.This article presents a case of intracranial air following intraspinal anesthesia performed using the normal saline resistance method.The patient was a 38-year-old female who underwent elective intraspinal anesthesia for 1 week without obvious cause of perianal swelling and pain.The procedure included incision and drainage of perianal abscess,excision of anal fistula with internal thread insertion,mixed hemorrhoid exfoliation and internal ligation,and electrocautery of anal papilloma.On the second postoperative day,she experienced headaches,dizziness,severe neck and back pain,along with numbness in the arms and inability to touch or move them.Resting in a supine position did not alleviate the symptoms.Head CT revealed scattered multiple air collections in the cranial cavity,with a total volume of approximately 3 mL.After a multidisciplinary consultation,symptomatic supportive treatment including bed rest,fluid supplementation,oxygen therapy,and anti-inflammatory and analgesic treatment was administered,leading to improvement and discharge.Follow-up at 6 months showed no discomfort.Currently,intracranial air is mostly associated with the air insufflation resistance test,while cases following the normal saline resistance method are rare,with unclear pathophysiological mechanisms,diagnosis,treatment,and prevention,necessitating further research.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the effects and underlying mechanisms of microRNA (miR)-34a on isoflurane anesthesia-induced cognitive dysfunction in aged rats. Methods Forty rats at 20 months of age were randomly divided into control (Con) group, model group, miR-34a inhibitor group and miR-34a mimics group, with 10 rats in each group. Rats in the miR-34a inhibitor and miR-34a mimics groups received a tail vein injection of 100 nmoL/kg of the corresponding drug, while those in the Con and model groups received an equal volume of saline, once daily for 5 consecutive days. At the 6th day, all groups except the Con group underwent a single 6-hour isoflurane anesthesia to establish a postoperative cognitive dysfunction (POCD) model. Twelve hours after modeling, the Morris water maze test was used to assess the escape latency and time spent in the target quadrant. Immunofluorescence staining was performed to observe the positive expression rate of ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampal tissue. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure the relative expression levels of miR-34a, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X-protein (Bax) mRNA in the hippocampal tissue. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect serum levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), reactive oxygen species (ROS) and glutathione peroxidase (GSH-Px), as well as the content of glutamate (Glu), Ca²⁺ and N-methyl-D-aspartate receptor 2B (NMDAR2B) in the hippocampal tissue. Western blotting was used to determine the relative expression levels of calcium-calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated CaMKⅡ (pCaMKⅡ), cyclophosphoadenosine effector-binding protein (CREB), and phosphorylated CREB (pCREB) in the hippocampal tissue. Results Compared with the Con group, the Model group exhibited significantly prolonged escape latency, elevated serum levels of IL-6 and IL-1β and ROS, as well as increased positive expression rate of Iba-1, relative expression levels of miR-34a and Bax mRNA, contents of Glu, Ca²⁺ and NMDAR2B in the hippocampal tissue; in contrast, the time spent in the target quadrant, serum GSH-Px levels, Bcl-2 mRNA relative expression levels, Bcl-2/Bax, as well as pCaMKⅡ/CaMKⅡ and pCREB/CREB in the hippocampal tissue were significantly reduced (P < 0.05). Downregulation of miR-34a expression shortened the escape latency and decreased serum levels of IL-6, IL-1β and ROS, as well as Iba-1 positive expression rate, relative expression levels of miR-34a and Bax mRNA, Glu, Ca²⁺ and NMDAR2B content in the hippocampal tissue (P < 0.05). It also extended the time spent in the target quadrant and increased serum GSH-Px levels, Bcl-2 mRNA expression levels, Bcl-2/Bax, as well as pCaMKⅡ/CaMKⅡ and pCREB/CREB in the hippocampal tissue (P < 0.05). Upregulation of miR-34a expression promoted abnormal activation of microglia, inflammation, oxidative stress and apoptosis, inhibited the activation of the CaMKⅡ/CREB signaling pathway, and exacerbated cognitive dysfunction in the model rats. Conclusion MiR-34a is highly expressed in POCD in aged rats. Inhibition of miR-34a expression can improve isoflurane anesthesia-induced cognitive dysfunction in aged rats by activating the CaMKⅡ/CREB signaling pathway.