Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

Animal experiments are an essential component of life sciences and medical research. However, the external validity and reliability of individual animal studies are frequently challenged by inherent limitations such as small sample sizes, high design heterogeneity, and poor reproducibility, which impede the effective translation of research findings into clinical practice. Systematic reviews and meta-analysis represent a key methodology for integrating existing evidence and enhancing the robustness of conclusions. Currently, however, the application of systematic reviews and meta-analysis in the field of animal experiments lacks standardized guidelines for their conduct and reporting, resulting in inconsistent quality and, to some extent, diminishing their evidence value. To address this issue, this paper aims to systematically delineate the reporting process for systematic reviews and meta-analysis of animal experiments and to propose a set of standardized recommendations that are both scientific and practical. The article's scope encompasses the entire process, from the preliminary preparatory phase [including formulating the population， intervention， comparison and outcome （PICO） question, assessing feasibility, and protocol pre-registration] to the key writing points for each section of the main report. In the core methods section, the paper elaborates on how to implement literature searches, establish eligibility criteria, perform data extraction, and assess the risk of bias, based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis （PRISMA) statement, in conjunction with relevant guidelines and tools such as Animal Research： Reporting of in Vivo Experiments （ARRIVE) and a risk of bias assessment tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). For the presentation of results, strategies are proposed for clear and transparent display using flow diagrams and tables of characteristics. The discussion section places particular emphasis on how to scientifically interpret pooled effects, thoroughly analyze sources of heterogeneity, evaluate the impact of publication bias, and cautiously discuss the validity and limitations of extrapolating findings from animal studies to clinical settings. Furthermore, this paper recommends adopting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to comprehensively grade the quality of evidence. Through a modular analysis of the entire reporting process, this paper aims to provide researchers in the field with a clear and practical guide, thereby promoting the standardized development of systematic reviews and meta-analysis of animal experiments and enhancing their application value in scientific decision-making and translational medicine.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

OBJECTIVES: To explore the synthesis of high-quality CT (sCT) from cone-beam CT (CBCT) using PE-CycleGAN for adaptive radiotherapy (ART) for nasopharyngeal carcinoma. METHODS: A perception-enhanced CycleGAN model "PE-CycleGAN" was proposed, introducing dual-contrast discriminator loss, multi-perceptual generator loss, and improved U-Net structure. CBCT and CT data from 80 nasopharyngeal carcinoma patients were used as the training set, with 7 cases as the test set. By quantifying the mean absolute error (MAE), peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), as well as the dose gamma pass rate and the relative dose deviations of the target area and organs at risk (OAR) between sCT and reference CT, the image quality and dose calculation accuracy of sCT were evaluated. RESULTS: The MAE of sCT generated by PE-CycleGAN compared to the reference CT was (56.89±13.84) HU, approximately 30% lower than CBCT's (81.06±15.86) HU (P<0.001). PE-CycleGAN's PSNR and SSIM were 26.69±2.41dB and 0.92±0.02 respectively, significantly higher than CBCT's 21.54±2.37dB and 0.86±0.05 (P<0.001), indicating substantial improvements in image quality and structural similarity. In gamma analysis, under the 2 mm/2% criterion, PE-CycleGAN's sCT achieved a pass rate of (90.13±3.75)%, significantly higher than CBCT's (81.65±3.92)% (P<0.001) and CycleGAN's (87.69±3.50)% (P<0.05). Under the 3 mm/3% criterion, PE-CycleGAN's sCT pass rate of (90.13±3.75)% was also significantly superior to CBCT's (86.92±3.51)% (P<0.001) and CycleGAN's (94.58±2.23)% (P<0.01). The mean relative dose deviation of the target area and OAR between sCT and planned CT was within ±3% for all regions, except for the Lens Dmax (Gy), which had a deviation of 3.38% (P=0.09). The mean relative dose deviations for PTVnx HI, PTVnd HI, PTVnd CI, PTV1 HI, PRV_SC, PRV_BS, Parotid, Larynx, Oral, Mandible, and PRV_ON were all less than ±1% (P>0.05). CONCLUSIONS PE-CycleGAN demonstrates the ability to rapidly synthesize high-quality sCT from CBCT, offering a promising approach for CBCT-guided adaptive radiotherapy in nasopharyngeal carcinoma.
Humans ; Cone-Beam Computed Tomography/methods* ; Nasopharyngeal Neoplasms/diagnostic imaging* ; Nasopharyngeal Carcinoma/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods* ; Radiotherapy Dosage ; Signal-To-Noise Ratio ; Radiotherapy, Intensity-Modulated

Objective To explore the value of one-stop spectral CT scanning of computer tomography pulmonary angiography(CTPA)combined with abdominal-pelvic enhancement in preoperative evaluation for patients with gynecological tumors.Methods Ninety-six patients with gynecological tumors who received both spectral CTPA and abdominal-pelvic enhanced CT examination at Zhongshan Hospital(Xiamen Branch),Fudan University,between January 2022 and December 2023 were collected.The conventional scanning group(n=48)received two independent spectral CT scans with twice contrast injections,while the one-stop scanning group(n=48)received one-stop spectral CTPA and abdominal-pelvic enhancement with once contrast injection.Virtual monochromatic images(VMIs)at 65 keV for CTPA,50 keV VMIs for abdominal-pelvic enhancement,contrast-enhanced iodine maps and effective atomic number images for the two parts were generated for all patients.The scanning parameters such as contrast agent dose,scanning duration,objective parameters of the images(CT values,iodine concentration,effective atomic number,etc.),as well as overall image quality score,the confidence score in diagnosing pulmonary embolization(PE),and the conspicuity of gynecological tumors were compared between the two groups.Results A total of 24 cases(25% )of PE were found in 96 patients.Compared with the conventional scanning group,the one-stop scanning group showed a significant reduction in contrast agent dosage([62.88±3.59]mL vs[98.52±2.63]mL,P＜0.001)and scan duration([95.94±0.38]s vs[108.91±0.35]s,P＜0.001).There was no statistically significant difference in dose length product(DLP),volume CT dose index,and effective dose(ED)between the two groups.There was no statistically significant difference in objective parameters and subjective image scores between the two groups of patients'CTPA images,abdominal and pelvic CT plain scans,and enhanced images.All image scores were≥3 points,meeting the diagnostic requirements.There was no statistically significant difference of confidence score in diagnosing PE and the ability to display tumor lesions between the two groups.Conclusions In comparison to conventional scanning,one-stop spectral scanning provides comparable image quality,confidence in diagnosing PE,and the conspicuity of gynecological tumors under a lower contrast agent dosage,a shorter scanning time,and a less patient waiting time in the preoperative evaluation for patients with gynecologic tumors,which is highly valuable.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective:To explore a definition of healthy longevity in the Chinese population based on the Delphi method.Methods:Through a comprehensive literature review and expert consultation, the dimensions in the definition of healthy longevity were identified, and a preliminary list of questions was created. Experts in clinical medicine, public health, basic research, and the elderly care service industry, who had been working in the field of geriatric health for at least 5 years, were invited to participate in the Delphi survey from August to December 2022. The survey questionnaires were administered via email in two rounds, and experts were asked to select the optimal options from the provided questions. The active coefficients were expressed by the response rate, and a consensus was reached when the largest number of experts agreed for single-choice questions and more than 70% agreed for multiple-choice questions.Results:In the two rounds, the active coefficients were 96.00% (24/25) and 79.17% (19/24), respectively, and a consensus was finally reached on nine items, including age, physical health, common metabolic indicators, mental health, cognitive function, functional ability, social activity, self-rated health, and subjective well-being. Following discussions among the research team and experts, a final definition of healthy longevity was determined. Healthy longevity could refer to a state of good physical, psychological, cognitive function and social adaptation, as well as subjective well-being, in individuals aged 90 and above. Specifically, individuals with healthy longevity should be free from diseases associated with high disability rates and mortality, such as stroke, cancer, and Parkinson′s disease. They should also maintain reasonable levels of common non-communicable disease indicators, such as blood pressure and blood glucose, and exhibit favorable mental health and cognitive function using validated measurement tools. In addition, individuals with healthy longevity should engage in social interactions with friends and relatives, care for family members, and go out to do things. Meanwhile, with the ability to complete the visual and hearing functions of daily life and communication, and the ability to complete basic activities such as walking, eating, bathing, toileting, dressing, continence of urination, and bowel movement independently, they could rate themselves to be in good health and experience a relatively high level of life satisfaction.Conclusion:A definition of healthy longevity in the Chinese population is established through the two-round Delphi consultation.

Objective To analyze the influence of different processing methods,including frying,ginger frying,and salt frying,on the volatile components of A.fructus.Methods The volatile components in different processed products of A.fructus were detected and analyzed by gas chromatography-mass spectrometry(GC-MS)based on multivariate statistical analysis.After OPLS-DA analysis,the different components were screened under the conditions of VIP＞1.5 and P＜0.05 and were qualitatively searched using the NIST 11 spectral library.Results A total of 49 different components were identified,with 14 components only changing in the seed mass and 22 components changing in the peel.The content of camphor could be significantly reduced in the seed mass after A.fructus was processed and the content of bornyl acetate significantly increased in the peel of frying A.fructus.Salt frying had a great influence on the alkanes in A.fructus,and ginger processing did not only increase the volatile components in ginger,which reflected the complexity of the processing mechanism.Conclusion At present,the specific processing mechanism is not clear,but the experimental results provide theoretical data for the "detoxification and efficiency enhancement" effect of A.fructus processing,reflecting the scientific nature of the processing,enriching the processing theory of A.fructus,and providing a reference for further in-depth research on the activity of different processed products of A.fructus.

To investigate the differences in methylation levels of cuproptosis related genes in cervical cancer and their effects on clinical prognosis.Methods:The methylation data of 310 cervical tissue specimens were acquired from public databases. The UALCAN database was used to analyze the methylation level differences of 12 cuproptosis-related genes and study their level in different stages or grades of cervical cancer. Genes with statistically significant differences were selected for prognosis analysis using the EWAS datahub. Finally, gene-enrichment analysis, pathway analysis, immune infiltration analysis, the mutation rate and tumor mutation burden (TMB) of the genes in cervical cancer were analyzed using the cBioportal database. Two independent samples rank-sum test was used for differences in methylation levels and immune cell infiltration; comparative analyses of overall survival were performed using KM survival curves and Log-rank two-sided tests. TMB analyses were performed using the Wilcoxon Test for statistical analyses; Pearson correlation analysis was used for assessment in GSEA and pathway analyses.Results:The methylationβvalue of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A gene) in the cervical cancer tissues of patients was 0.075 which was significantly higher than the methylationβvalue of 0.049 in normal human tissues ( P=0.008). Dihydrolipoamide S-Acetyltransferase (DLAT gene) methylation with a β value of 0.102 was significantly higher than normal human tissue methylation with a β value of 0.08 ( P=0.002), and the methylation level β value of Lipoyltransferase 1 (LIPT1 gene) in cervical cancer tissues was 0.06,which was significantly lower than normal human tissue methylation value of 0.092 ( P=0.009). Patients with CDKN2A gene methylation levels≥0.199 had an overall survival of 14.75 years, which was lower than that of patients with methylation levels<0.199 (17.56 years) ( P=0.034).The results of gene enrichment analysis indicated that it mainly involves biological processes such as the response to type I interferon and DNA replication. The expression of CDKN2A gene is positively correlated with the number of neutrophils and dendritic cells in the tumor microenvironment( P<0.05), and negatively correlated with the number ofmacrophages( P<0.05). TMB was higher in the group of variants of the CDKN2A gene than in the group of non-variants ( P=0.019). Conclusion:CDKN2A methylation is a potential biomarker for predicting the prognosis of cervical cancer.

Objective To investigate the clinicopathological and prognostic characteristics of intestinal inflammatory myofibroblastic tumours(IMT)in middle-aged and elderly patients.Methods The clinical,pathologi-cal morphology,immunophenotype and follow-up results of 5 cases of intestinal IMT in middle-aged and elderly patients were retrospectively analyzed.Results 4 cases of IMT occurred in the right half colon and 1 in the ileum.Most patients(3/5)had a history of intestinal injury,starting the digestive tract symptoms and increased leukocytes.The tumor tissue was composed of fusiform myofibroblasts and fibroblasts arranged in storiform pattern,with an infiltrative growth pattern,accompanied by a large number of lymphocytes and plasma cells infiltration,collagen formation and myxedema.One case was atypically large and deformed.Immunophenotype:vimentin(5cases),SMA(5 cases),desmin(3 cases),ALK(3 cases),CK(2 cases)were positive.Caldesmon,CD34,β-catenin,MC,CD117,DOG1,S-100,BCL-2,CD99,CD68 were negative,and Ki-67 proliferation index was 1.28%to 10.01%.All the 5 cases underwent complete tumor resection and were followed up for 48.5 to 133 months.Among them,1 patient aged 83 was considered to have tumor recurrence 27 months after surgery.The other patient survived 122 months without tumor and died of other causes.All the others survived without tumor and were in good condition.Conclusion(1)Intestinal IMT in the middle-aged and elderly people in this group was more common in the right half colon,and most of them had a history of intestinal injury,first gastrointestinal symptoms and elevated white blood cells;(2)Vimentin and SMA were positive at the same time,and ALK was more positive;(3)4/5 patients had good surgical resection,and 1/5 patients could relapse 2～3 years after surgery;old age,ALK-positive,Ki67 up to 10%,atypia may be an important risk factor for intestinal IMT recurrence in the elderly,of which ALK-positive patients may have a recurrence risk of 1/3.