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.

OBJECTIVE: To investigate the effectiveness of Holosight robotic navigation-assisted percutaneous cannulated screw fixation for femoral neck fractures. METHODS: A retrospective analysis was conducted on 65 patients with femoral neck fractures treated with cannulated screw fixation between January 2022 and February 2024. Among them, 31 patients underwent robotic navigation-assisted screw placement (navigation group), while 34 underwent conventional freehand percutaneous screw fixation (freehand group). Baseline characteristics, including age, gender, fracture side, injury mechanism, Garden classification, Pauwels classification, and time from injury to operation, showed no significant differences between the two groups ( P>0.05). The operation time, intraoperative blood loss, fluoroscopy frequency, fracture healing time, and complications were recorded and compared, and hip function was evaluated by Harris score at last follow-up. Postoperative anteroposterior and lateral hip X-ray films were taken to assess screw distribution accuracy, including deviation from the femoral neck axis, inter-screw parallelism, and distance from screws to the femoral neck cortex. RESULTS: No significant difference was observed in operation time between the two groups ( P>0.05). However, the navigation group demonstrated superior outcomes in intraoperative blood loss, fluoroscopy frequency, deviation from the femoral neck axis, inter-screw parallelism, and distance from screws to the femoral neck cortex ( P<0.05). No incision infections or deep vein thrombosis occurred. All patients were followed up 12-18 months (mean, 16 months). In the freehand group, 1 case suffered from cannulated screw dislodgement and nonunion secondary to osteonecrosis of femoral head at 1 year after operation, 1 case suffered from screw penetration secondary to osteonecrosis of femoral head at 5 months after operation; and 1 case suffered from nonunion secondary to osteonecrosis of femoral head at 6 months after operation in the navigation group. All the 3 patients underwent internal fixators removal and total hip arthroplasty. There was no significant difference in the incidence of complications between the two groups ( P>0.05). The fracture healing time and hip Harris score at last follow-up in the navigation group were significantly better than those in the freehand group ( P<0.05). CONCLUSION Compared to freehand percutaneous screw fixation, Holosight robotic navigation-assisted cannulated screw fixation for femoral neck fractures achieves higher precision, reduced intraoperative radiation exposure, smaller incisions, and superior postoperative hip function recovery.
Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Screws ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Middle Aged ; Aged ; Adult ; Treatment Outcome ; Operative Time ; Fracture Healing ; Surgery, Computer-Assisted/methods* ; Fluoroscopy

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

OBJECTIVE: To assess the effectiveness of the single Kocher-Langenbeck approach combined with anterograde channel screw technique for the treatment of acetabular transverse and posterior wall fractures. METHODS: Between March 2020 and October 2022, 17 cases of acetabular transverse and posterior wall fractures were treated with the single Kocher-Langenbeck approach combined with anterograde channel screw technique. There were 11 males and 6 females, with an average age of 53.6 years (range, 42-64 years). Causes of injury included traffic accident in 12 cases, and falling from height in 5 cases. The time from injury to operation ranged from 4 to 16 days with an average of 8.8 days. The operation time, intraoperative blood loss, and fluoroscopy frequency were recorded; X-ray films were reviewed regularly after operation to observe the fracture healing, and postoperative complications were recorded. At last follow-up, Matta score was used to evaluate the reduction of fracture, Harris score and modified Merle D'Aubigné-Postel scores system were used to evaluate the hip joint function. RESULTS: The operation time was 150-230 minutes (mean, 185.9 minutes), the intraoperative blood loss was 385-520 mL (mean, 446.2 mL), and the fluoroscopy frequency was 18-34 times (mean, 27.5 times). Postoperative fat liquefaction occurred in 1 case and the other incisions healed by first intention; 3 cases had limb numbness after operation, and the symptoms disappeared after active symptomatic treatment; no urogenital system and intestinal injury occurred. All patients were followed up 12-28 months (mean, 19.9 months). Bone union was achieved in all cases with an average healing time of 10.8 weeks (range, 8-14 weeks). There was no complication such as loosening and breakage of internal fixators. At last follow-up, according to Matta score, 12 cases achieved anatomic reduction, 3 satisfactory reduction, and 2 fair reduction, the satisfactory rate was 88.2%; according to Harris hip function score, 12 cases were excellent, 3 good, and 2 fair, the excellent and good rate was 88.2%; according to the modified Merle D'Aubign Aubigné-Postel scoring system, the results were excellent in 11 cases, good in 3 cases, and fair in 3 cases, with an excellent and good rate of 82.4%. CONCLUSION The single Kocher-Langenbeck approach combined with anterograde channel screw technique is a minimally invasive method for the treatment of acetabular transverse and posterior wall fractures with less complications, simple operation, and satisfactory effectiveness.
Male ; Female ; Humans ; Middle Aged ; Blood Loss, Surgical ; Fracture Fixation, Internal/methods* ; Treatment Outcome ; Fractures, Bone/surgery* ; Acetabulum/injuries* ; Bone Screws ; Hip Fractures/surgery* ; Retrospective Studies

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.

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by inflammation due to neutrophil infiltration, has become the third leading cause of death worldwide. After the occurrence of COPD, the persistent accumulation of neutrophils can promote the excessive formation of neutrophil extracellular traps (NETs), which plays an important role in local capture and clearance of pathogens, rapid control of infection, and immune regulation. This article mainly introduces the mechanism of COPD occurrence and NETs formation as well as the research progress of NETs in COPD, and summarizes the relevant drug targets for COPD treatment based on NETs, aiming to provide a reference for further research.

Ischemic stroke, a cerebrovascular disease with high incidence, high mortality, high disability rate and high recurrence rate, is an important cause of death and disability of middle-aged and elderly people in China, and imposes a huge burden to society and families. Therefore, it is essential to identify the risk factors associated with ischemic stroke and effectively prevent them. Studies have shown that obstructive sleep apnea is an independent risk factor for ischemic stroke. However, the exact pathological mechanism of their association has not been clarified. With the development of next-generation sequencing technology, more and more studies have focused on intestinal microbiota. They have found that obstructive sleep apnea can cause intestinal microbiota changes, and intestinal microbiota may be closely related to ischemic stroke. Therefore, this paper attempts to investigate the relationship between intestinal flora and ischemic stroke, so as to reveal the potential pathological mechanism of ischemic stroke caused by obstructive sleep apnea.

Mesenchymal stem cells(MSCs)are self-regenerating,rapidly proliferating pluripotent stem cells that depend primarily on their derived pro-angiogenic,inflammatory regulatory,and tro-phic factors to exert beneficial effects that attenu-ate deleterious inflammatory responses,reduce vascular damage,and promote tissue repair and re-generation.Obstructive sleep apnea hypoventila-tion syndrome(OSAHS)is a chronic disorder marked by oropharyngeal collapse during sleep,re-sulting in transient reduced airflow,large fluctua-tions in intrathoracic pressure,and intermittent hy-poxia and hypercapnia.OSAHS subsequently cyto-kine-mediated inflammatory cascades,oxidative stress,and ischemia,recruit MSCs from inflamed and damaged tissues through MSCs-derived of anti-inflammatory and pro-angiogenic factor activity,re-duce hypoxia,suppress inflammation,promote re-generation,and prevent fibrosis in OSAHS-injured tissues.In this paper,we will describe the patho-genesis of inflammation,oxidative stress,fibrosis and ischemia from the perspective of OSAHS,high-lighting the current research progress on MSCs-de-pendent regulation of OSAHS-related pathology.

Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.