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 observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To analyze the clinical effect of vitamin D combined with budesonide suspension in the treatment of Mycoplasma pneumoniae pneumonia in children and the influence on peripheral blood T lymphocyte subsets and serum interleukin-17(IL-17)and hypersensitive C-reactive protein(hs-CRP).Methods Children with severe Mycoplasma pneumoniae pneumonia were classified into control group and treatment group by adopting the random number table method.The control group was treated with budesonide aerosol inhalation therapy(1 mL for ≤7 years old,2 mL for＞7 years old,twice a day for 2 weeks),and the treatment group was additionally given oral administration of vitamin D(400 U,once a day for 2 weeks).The clinical effect,disappearance times of clinical symptoms and signs,peripheral blood T lymphocyte subsets,serum IL-17,hs-CRP and 25-hydroxy vitamin D(25(OH)D)and occurrence of adverse drug reactions were compared between both groups of children.Results Eleven cases dropped out during treatment,and finally forty cases were included in treatment group and control group respectively.After treatment,the total effective rates in treatment group and control group were 97.50％(39 cases/40 cases)and 82.50％(33 cases/40 cases);the cough disappearance times were(5.14±1.08)and(6.87±1.24)d;the rale disappearance times were(6.69±1.21)and(8.52±1.29)d;CD3+levels were(68.03±5.68)％and(64.61±6.84)％;CD4+levels were(44.26±5.83)％and(39.94±5.01)％;CD4+/CD8+levels were 1.37±0.33 and 1.24±0.21;serum IL-17 levels were(22.84±4.13)and(39.21±8.68)pg·mL-1;hs-CRP levels were(3.25±0.72)and(6.07±1.11)mg·L-1;25(OH)D levels were(36.42±6.86)and(24.25±6.03)ng·mL-1,respectively(all P＜0.05).During the treatment period,the adverse drug reactions of the two groups were mainly diarrhea,vomiting,abdominal discomfort and throat irritation.The total incidence of adverse drug reactions in treatment group and control group was 22.50％and 17.50％,respectively,and there was no statistically significant difference(P＞0.05).Conclusion Vitamin D combined with budesonide suspension has a significant clinical effect in the treatment of Mycoplasma pneumoniae pneumonia in children,and it can effectively relieve symptoms,regulate the levels of T lymphocyte subsets,and reduce the levels of serum IL-17 and hs-CRP,with good safety.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

OBJECTIVE: To evaluate the effect of manual acupuncture on endometrial blood flow parameters by three-dimensional (3D) power Doppler ultrasound in women undergoing in vitro fertilization embryo transfer (IVF-ET). METHODS: Seventy patients undergoing IVF-ET were equally randomized into traditional or sham acupuncture treatment group for totally 4 days (from the day of oocyte aspiration to the day of embryo transfer) of treatment by random envelope method at the Reproductive Medicine Center and Outpatient Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology from January 2013 to December 2015. Patients in the traditional acupuncture group accepted traditional acupuncture methods with manual acupuncture, and Zhongji (CV3), Qihai (CV 6), Sanyinjiao (SP6), Taichong (LR 3), Tianshu (ST 25), Guilai (ST 29) and Zusanli (ST 36) were chosen. Patients at the sham acupuncture group accepted shallow acupuncture methods at 4 non-meridian points at each shoulder and upper arm. Outcome measures included endometrial ultrasonic indices such as vascularization index (VI), flow index (FI) and vascularization flow index (VFI), endometrial thickness and volume, subendometrial VI (sVI), subendometrial FI (sFI), subendometrial VFI (sVFI), implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births. RESULTS: Finally, 34 patients in the traditional acupuncture group and 35 in the sham acupuncture group completed this trial. VI, FI and VFI of the traditional acupuncture group were significantly higher than those in the sham acupuncture group (P<0.05). No significant differences were found in endometrial thickness, endometrial volume, sVI, sFI, sVFI, implantation rate, clinical pregnancy rate, abortion rate, live birth rate and number of live births (P>0.05). CONCLUSIONS Manual acupuncture performed after oocyte aspiration and before transplantation improved the endometrial blood flow parameters VI, RI and VFI in women who underwent IVF-ET, instead of sVI, sFI and sVFI. Therefore, acupuncture might be beneficial in women undergoing IVF-ET by increasing endometrial blood flow and endometrial receptivity. (Registration No. ChiCTR2100053354).
Pregnancy ; Humans ; Female ; Fertilization in Vitro/methods* ; Single-Blind Method ; Embryo Transfer ; Pregnancy Rate ; Acupuncture Therapy ; Endometrium/blood supply*

Objective To systematically evaluate the short-term efficacy and safety of lung subsegmentectomy and segmentectomy in the treatment of small pulmonary nodules. Methods Computer searches were conducted on PubMed, The Cochrane Library, EMbase, Scopus, Web of Science, SinoMed, Wanfang Data, VIP, and CNKI databases to collect relevant literature on the short-term efficacy and safety of lung subsegmentectomy and segmentectomy for small pulmonary nodules from the inception to April 2024. Two researchers independently screened the literature and extracted data according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software, and the Newcastle-Ottawa Scale (NOS) was used to assess the quality of the selected literature. Results A total of 15 retrospective cohort studies with 2417 patients were included, among whom 796 patients underwent lung subsegmentectomy and 1621patients underwent segmentectomy. The NOS scores of the included literature were all≥6 points. Meta-analysis results showed that compared with segmentectomy, lung subsegmentectomy had a lower overall postoperative complication rate [OR=0.54, 95%CI (0.39, 0.75), P<0.01] and fewer lymph nodes dissected [MD=−0.43, 95%CI (−0.81, −0.06), P=0.02]. There was no statistical difference between the two surgical methods in terms of operation time [MD=5.11, 95%CI (−4.02, 14.23), P=0.27], intraoperative blood loss [MD=−14.62, 95%CI (−29.58, 0.34), P=0.06], postoperative hospital stay [MD=−0.24, 95%CI (−0.49, 0.01), P=0.06], postoperative drainage time [MD=−0.14, 95%CI (−0.46, 0.18), P=0.40], intraoperative margin width [MD=0.10, 95%CI (−0.16, 0.35), P=0.46], or recurrence rate [OR=1.57, 95%CI (0.53, 4.61), P=0.42]. Subgroup analysis results showed that when using uniportal video-assisted thoracoscopy for surgery, compared with segmentectomy, lung subsegmentectomy had less intraoperative blood loss [MD=−15.57, 95%CI (−28.84, −2.30), P=0.02], shorter postoperative hospital stay [MD=−0.49, 95%CI (−0.63, −0.35), P<0.01], shorter postoperative drainage time [MD=−0.19, 95%CI (−0.35, −0.03), P=0.02], and lower overall complication rate [OR=0.55, 95%CI (0.31, 0.98), P=0.04]. Conclusion Lung subsegmentectomy can achieve similar efficacy as segmentectomy and has a lower overall postoperative complication rate. In terms of safety, lung subsegmentectomy can achieve a margin range close to that of segmentectomy. When performing uniportal thoracoscopic surgery, lung subsegmentectomy has advantages over segmentectomy in terms of intraoperative blood loss, postoperative hospital stay, and drainage time.

The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min^-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.

【Objective】 To summarize the clinicopathological features and prognosis of young patients (18-40 years old) with non-clear cell renal cell carcinoma (nccRCC) treated in a single center to provide reference for the diagnosis and treatment of similar patients. 【Methods】 Clinical data of 113 nccRCC patients treated during Jan. 2012 and Aug. 2022 were retrospectively analyzed, including 57 males (50.4%) and 56 females (49.6%). The average age of onset was (31.6±5.8) years. Among all patients, 57 had lesions (50.4%) on the left side, and 56 (49.6%) on the right side. Young patients undergoing renal cancer surgery accounted for approximately 12.4% of the total number of renal cancer patients undergoing surgery, and nccRCC accounted for 34.8% of the total number of cases. 【Results】 Minimally invasive surgery (laparoscopic or robot-assisted) was performed in 102 cases (90.3%), and open surgery in 11 cases (9.7%). Fifty-five cases (48.7%) underwent partial nephrectomy and 58 (51.3%) radical nephrectomy. Among them, 11 patients (9.7%) developed tumor thrombi. All surgeries were successful with no serious complications. The pathological types included 32 cases (28.3%) of chromophobe renal cell carcinoma, 25 cases (22.1%) of MiT family translocation renal cell carcinoma, and 20 cases (17.7%) of papillary renal cell carcinoma. The total proportion of the three pathological subtypes reached 68.1%. After 46 (2-115) months of follow-up, 8 cases (7.8%, 8/102) developed tumor metastasis and 2 died. 【Conclusion】 The nccRCC is rare in young patients. The major pathological type is chromophobe, and the major treatment method is minimally invasive surgery. Most pathological types have good long-term prognosis, while patients with tumor thrombi have a high risk of metastasis and poor prognosis.

BACKGROUND:There is controversy regarding the need for marrow reaming in intertrochanteric fractures of the femur.Some believe that unreaming shortens operative time,reduces bleeding,and decreases intraoperative risk in elderly patients,but there is no basis for whether this move reduces the effectiveness of intramedullary nail support.Others believe that reaming allows for the selection of thicker diameter intramedullary nails for better mechanical support,but basic studies have shown that this approach carries risks such as fat embolism and destruction of bone(especially in elderly patients with osteoporosis). OBJECTIVE:To analyze the mechanical distribution characteristics of reamed and unreamed proximal femoral nail antirotation-Ⅱ in the treatment of type 31-A3 intertrochanteric fractures by finite element analysis. METHODS:A healthy volunteer was included,and CT scans of his femur were obtained in DICOM format,and the files were sequentially imported into Mimics,Geomagic Wrap,SolidWorks,Hypermesh,and Ansys software for processing.The A3.1,A3.2,and A3.3 intertrochanteric fracture models were obtained and assembled with 9 mm,11 mm diameter,and 170 mm length intramedullary nails,respectively,followed by assigning material properties,setting the interaction relationship of each contact surface and defining the load and boundary conditions,and then solved.The femoral stress distribution,internal fixation stress distribution,femoral displacement,and internal fixation displacement were observed in different models. RESULTS AND CONCLUSION:(1)The femoral stress was less than that of unreamed intramedullary nail fixation for each type of fracture,and the maximum stress value of the femur for A3.3 fracture was greater than that of A3.1 and A3.2.(2)The internal fixation stress was greater than that of unreamed intramedullary nail fixation for each type of fracture,and the maximum stress value of internal fixation for A3.3 fracture was greater than that of A3.1.(3)Reamed versus unreamed intramedullary nailing has less effect on femoral and internal fixation displacement and more effect on stress.(4)It is indicated that the use of reamed intramedullary nail fixation results in a reduction in femoral stress,an increase in the stress borne by the internal fixation as a whole,and a reduction in the stress borne by the distal locking nail.The use of reamed intramedullary nail fixation may provide better treatment results compared to unreamed intramedullary nail fixation.