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 summarize the current research status and cutting-edge trends of the off-label drug use in China,with a view to providing reference for researchers in this field.Methods CNKI and SinoMed databases were searched to collect research of the off-label drug use in China,and used Microsoft Excel 2021,the R software Bibliometric,and VOSviewer 1.6.18 to visualize the time and trend of publication,province,issuing authors and units,journals,keywords,and topic evolution of the included studies.Results 1 475 papers were included in the research.A total of 2 808 authors from 31 provinces,cities and regions had conducted relevant studies on over-the-counter medication,with an overall increasing trend in the number of publications.Among them,Guangdong province published the most studies related to this field,the Straits Pharmacy Journal and China Pharmacy published the most studies in this field.Proprietary Chinese medicines,antimicrobials,antitumor drugs,and other drugs were the research hotspots.In addition,the patients in pediatrics,outpatient emergency,obstetrics and gynecology,psychiatry and other departments as a special sick population,the clinical use of medication exists in the overspecification situation was also a future research trend.Conclusion At present,research in this field focuses more on OLDU for special populations,special diseases,special drugs,etc.In the future,researchers should conduct evidence-based evaluation of drugs on the basis of more high-quality evidence in order to seek the best evidence for guiding the clinical use of medication.At the same time,drug administration and medical institutions should also develop standardized management policies and systems to promote the rational and safe use of medication in healthcare institutions.

Objective:To evaluate the fixation with a locking fibular intramedullary nail for treatment of extra-articular distal tibial fracture complicated with fibular fracture (AO/OTA 43A).Methods:A retrospective study was conducted to analyze the data of 31 patients who had been treated by fixation with a locking fibular intramedullary nail for extra-articular distal tibial fracture complicated with fibular fracture at Department of Orthopaedics, The 909th Hospital of Joint Logistics Support Force between January 2018 and December 2021. There were 20 males and 11 females; (41.5±15.7) years in age; AO classification of the distal tibial fractures: 10 cases of type 43A1, 10 cases of type 43A2, and 11 cases of type 43A3; 11 open fractures and 20 closed fractures. Fracture healing, fibular alignment, tibiotalar angle, and incidence of complications were regularly followed up and recorded after surgery. At the last follow-up, the ankle joint function was assessed using the Olerud Molander ankle score (OMAS) and the ankle-hindfoot score of American Orthopaedic Foot and Ankle Society (AOFAS).Results:All the 31 patients were followed up for (17.5±3.3) months after surgery. All of them achieved fine fracture union. The union time was (3.9±0.8) months for tibial fractures, and (3.6±0.9) months for fibular fractures. No internal fixation failure was observed. The last follow-up revealed the following: the fibular alignment was 1.8°±1.3° and the ankle tibiotalar angle 9.1°±2.3°; no fibular rotation, shortening, or separation displacement happened; the OMAS score was (88.3±6.2) points, and the AOFAS ankle-hindfoot score (87.4±6.0) points. Two patients required removal of the distal locking screw of the fibular intramedullary nail due to soreness around the lateral malleolus caused by screw loosening. There were no other related complications.Conclusion:Fixation with a locking fibular intramedullary nail is an effective treatment for extra-articular distal tibial fracture complicated with fibular fracture, demonstrating advantages of firm fixation, limited complications, minimal trauma and soft tissue irritation, and good clinical efficacy.

Objective To analyze the distribution of carbapenem-resistant strains and the transmission mode of resistance genes in the bacteria strains from urinary system of the individuals outside hospitals,and further explore the impacts of the antibiotics with different antibacterial mechanisms on the conjugation transfer of resistant plasmids.Methods The imipenem-resistant strains from 991 non-re-petitive urine samples of healthy individuals were screened for determining the carbapenem-resistance genotypes.Using the multilocus sequence typing(MLST)method,the main carbapenem-resistant strains were classified to determine the phylogenetic relationship be-tween different sequence types(STs)and reveal the transmission mode of resistance genes in the individuals outside hospitals.The conjugation experiment was used to analyze the effects of different sub-inhibitory concentrations of ampicillin,ciprofloxacin,and genta-micin on the conjugation efficiency of resistant plasmids in the bacteria of donor and/or recipient at different times.Results A total of 18 non-repetitive carbapenem-resistant strains(1.82％,18/991)were detected in healthy individuals outside hospitals,among which Escherichia coli(E.coli)(44.44％,8/18)was the main strain with main genotype being blaKPC-2(7/8).MLST showed that the 7 strains of E.coli with blaKPC-2 genotype belonged to ST-10,ST-101,ST-131,ST-405,ST-410,ST-1193,and ST-2562,respectively.Homologous clustering analysis showed that the type of the 7 E.coli strains exhibited high diversity.The range of joint efficiency was(1.59±0.20)× 10-4 to(4.01±1.31)× 10-4.The highest conjugation efficiency was observed in the donor bacteria treated with 1/8 of MIC of antibiotics for 9 hours,and the conjugation efficiency most significantly increased compared to the group without antibiotic treat-ment.Three antibiotics with different mechanisms of action could all improve conjugation efficiency,among which ampicillin exhibited the most significant improvement.Conclusion In this study,the genotype of carbapenem-resistant Escherichia coli(CREC)was mainly blaKPC-2 with a main mode of horizontal transmission.Antibiotics with sub-inhibitory concentrations could promote the conjugation transfer of the resistant plasmid.There may be significant differences in the effects of antibiotics with different mechanisms of action and different antibiotic stress conditions on the conjugation efficiency.

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.

To investigate the initial experience of coated metal ureteral stent(CMUS)for treatment of pelvic lipomatosis induced hydronephrosis(PLH).The clinical and follow-up data of 8 patients who were diagnosed as PLH treated with CMUS in Peking University People's Hospital from August 2018 to February 2021 were retrospectively analyzed.Inclusion criteria included:Imaging evidence of excessive adipose tissue around the bladder in the pelvic cavity,bladder elevation in an"inverted pear shape",and bladder wall thickening;Cystoscopy indicated follicular hyperplasia of bladder mucosa and biopsy pathology indicated glandular cystitis;Unilateral or bilateral hydronephrosis and ureteromegaly.Exclusion criteria included:Ureteral atresia;Recurrent obstruction of the bladder outlet.Preoperative baseline data included age,gender,serum creatinine,pelvis width and ureteric stent symptoms questionnaire(USSQ)score.Intraoperative data included the location and length of ureteral stenosis observed by retrograde urography.Postoperative follow-up data included serum creatinine,pelvis width,and USSQ score.In the study,8 patients(11 sides)with PLH were all male,with an average age of(38.7±8.6)years.Uni-lateral hydronephrosis was found in 5 cases and bilateral hydronephrosis in 3 cases.Preoperative mean serum creatinine was(90.0±10.3)μmol/L,and the mean renal pelvis width was(3.0±1.5)cm.The lower ureteral stricture was found in all cases,and the mean stricture length was(1.9±0.9)cm.Before operation,3 patients had ureteral Double-J stents,with USSQ scores of 97.0,68.0 and 100.0,respectively.Five patients underwent retrograde CMUS stenting,and 3 patients retrograde and antegrade.At the last follow-up,the average serum creatinine was(82.0±11.1)μmol/L and the mean renal pel-vis width was(1.9±0.5)cm,which were significantly lower than those before operation(t=3.12,P=0.02;t=3.23,P=0.02).In the 3 patients with Double-J stent before surgery,the USSQ scores were 87.0,62.0 and 89.0,respectively,which were significantly improved after CMUS stenting.The average follow-up time was(10.0±6.3)months.During the follow-up,1 patient developed CMUS re-lated symptoms,and no stent-associated infection and stent encrustation were found.In one case,the stent migrated to the bladder 3 months after operation,and the hydronephrosis disappeared after 3 months follow-up.CMUS stenting for treatment of PLH has certain efficacy and safety,which can explore a new therapeutic method for the long-term treatment of PLH.

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.