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.

Type 2 diabetes mellitus （T2DM） and hypertension are common and frequent chronic non-communicable diseases， which often coexist in clinical practice， resulting in a large number of cardiovascular events and deaths， and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards， guidelines， and animal model evaluation methods of T2DM with hypertension at home and abroad， this study summarized， evaluated， and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin （STZ） in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine （TCM） are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages， the ideal modeling method for T2DM with hypertension is the two-kidney， one clip （2K1C） method （a surgical induction method） combined with feeding a high-fat and high-sugar diet and STZ injection. However， the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome， which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem， it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome， which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way， ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM， which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time， breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.

Type 2 diabetes mellitus （T2DM） and hypertension are common and frequent chronic non-communicable diseases， which often coexist in clinical practice， resulting in a large number of cardiovascular events and deaths， and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards， guidelines， and animal model evaluation methods of T2DM with hypertension at home and abroad， this study summarized， evaluated， and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin （STZ） in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine （TCM） are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages， the ideal modeling method for T2DM with hypertension is the two-kidney， one clip （2K1C） method （a surgical induction method） combined with feeding a high-fat and high-sugar diet and STZ injection. However， the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome， which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem， it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome， which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way， ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM， which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time， breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.

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.

The rupture of carotid vulnerable plaques is the core pathological basis for major cardiovascular and cerebrovascular events. However， the insufficient alignment between existing animal models and the clinical disease and syndrome characteristics of traditional Chinese and western medicine has limited research progress. In this study， biomedical databases in China and abroad were systematically searched， and the modeling mechanisms and evaluation systems of carotid vulnerable plaque animal models were systematically assessed based on diagnostic criteria of both traditional Chinese and western medicine. Analysis of the clinical correspondence indicated that existing animal models can be categorized into four types： simple high-fat diet， surgical induction combined with high-fat feeding， genetic engineering combined with high-fat feeding， and drug induction combined with high-fat feeding. Among these， the compound strategy of surgical induction combined with high-fat feeding has become the current mainstream approach， showing good concordance with western medicine. The study found that the double balloon injury rabbit model and the ApoE^-/- mouse carotid artery tandem constriction combined with high-fat feeding model demonstrated a high degree of clinical correspondence with both traditional Chinese and western medicine in terms of vulnerable plaque imaging and pathological features. Nevertheless， existing models still face significant technical limitations in faithfully simulating plaque pathology and in translating findings to clinical applications. To address these challenges， integrating complex comorbidity mechanism construction， multimodal dynamic mechanism monitoring， and collaborative evaluation systems of traditional Chinese and western medicine could enable the development of highly concordant carotid vulnerable plaque disease-syndrome combination animal models. Such models would provide a reproducible experimental platform for targeted drug development to regulate plaque stability and for individualized precision treatment， as well as a theoretical basis for innovation in clinical diagnostic and therapeutic strategies.

Objective:To explore the causal relationship between blood metabolites and keloids.Methods:The study was a two-sample bidirectional Mendelian randomization (MR) analysis-based study. Blood metabolites of 7 824 adult volunteers and 8 299 participants and data related to 481 912 keloid patients were obtained from the genome-wide association studies (GWAS) Catalog database. Single nucleotide polymorphisms (SNPs) significantly associated with blood metabolites and keloids were screened for inclusion as instrumental variables in the MR analysis by setting a significance threshold of P<1.0×10 -5, chain imbalance analysis [ r2 = 0.001, kilobase pairs (kb) = 10, 000)], and the F statistic ( F≥10) . Five method of MR analysis, i.e., inverse variance weighting (IVW) as the main method and MR-Egger regression, weighted median, simple modeling, and weighted modeling as auxiliary method, were used to analyze the causal relationship between blood metabolites (exposure factors) and keloids (outcome variables) . Sensitivity analyses were performed on eligible blood metabolite SNPs to assess the reliability and stability of the findings: heterogeneity was assessed by Cochran Q-test and MR-Egger regression test, MR Egger intercept test to rule out horizontal pleiotropy, leave-one-out test to determine if the presence of a single SNP significantly affected the result of the MR analyses, MR-PRESSO method was used to test for outliers of SNPs, which were corrected by false discovery rate (FDR) (FDR <0.2) to control the false positive rate. Reverse MR analysis was performed with keloid as the exposure factor, and blood metabolites screened by the aforementioned MR analysis were used as outcome variables for effect analysis and sensitivity analysis. The data were analyzed using R 4.3.2 software and the TwoSampleMR program package therein, and the causal effect values of the MR analysis were expressed as the ratio ( OR) and 95% CI, with P<0.05 being considered as a statistically significant difference, i. e., the evidence of a potential causal effect was substantial. Forest plots, funnel plots, and scatter plots were constructed to visualize the result of MR analysis and sensitivity analysis. Results:A total of 1 400 blood metabolites with 34 843 SNPs were obtained from the GWAS Catalog database, all of which were consistent with the hypothesis that genetic variants are closely associated with exposure factors; a total of 24 197 210 SNPs were obtained from the keloid dataset. IVW analysis revealed that one blood metabolite, succinyl taurine (16 ∶ 1n-7), had 28 SNPs with keloid with a causal relationship ( OR=1.13, 95% CI 1.06-1.19, P<0.001, FDR=0.070) ; MR-Egger regression method ( OR = 1.11, 95% CI 1.04-1.19, P=0.005), weighted median method ( OR = 1.11, 95% CI 1.02-1.20, P=0.014) and weighted modeling method ( OR=1.12, 95% CI 1.04 to 1.20, P=0.004) analyses also showed that succinyl taurine (16 ∶ 1n-7) was a risk factor for keloid disease; the result of the simple modeling method only showed that the causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid disease was not significant ( OR=1.10, 95% CI 0.85-1.41, P=0.485) . MR overall analysis showed a significant positive causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid, i.e., elevated levels of succinyl taurine (16 ∶ 1n-7) were associated with an increased risk of keloid disease. Cochran Q-test ( Q = 26.98, P=0.465), MR-Egger regression test ( Q = 26.65, P = 0.428), MR-Egger intercept test ( P = 0.574), and MR-PRESSO composite test ( P=0.569) showed that there was no heterogeneity and horizontal pleiotropy among SNPs ( P>0.05) ; the leave-one-out test confirmed that individual SNPs did not have a significant effect on the overall result, indicating that the result had reliability and stability. The inverse MR analysis suggested that there was no causal relationship between keloid on succinyl taurine (16 ∶ 1n-7) (IVW: OR=0.98, 95% CI 0.93-1.04, P=0.490) . Conclusions:There is a significant positive causal relationship between the blood metabolite succinyl taurine (16 ∶ 1n-7) and keloids, and succinyl taurine (16 ∶ 1n-7) is a risk factor for keloid disease.

Objective:To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas.Methods:This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results:After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [ M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group ( P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups( P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions:PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.

This study investigated the primary pathogenesis and syndrome evolution of different heart failure with preserved ejection fraction(HFpEF)stages based on the classical and clinical experience of traditional Chinese medicine(TCM),combined with the clinical characteristics of pre-heart failure,symptomatic heart failure,and advanced heart failure.This study summarizes and refines the three core syndrome factors:water,deficiency and blood stasis.Water-fluid retention was observed throughout these three stages,from the beginning to the end.With the advancement of the disease,the heart yang changes from stagnation to deficiency,water-fluid retention gradually increases,blood stasis becomes increasingly prominent,and the disease location develops dynamically from the upper to the middle and lower jiao.This study proposes three methods of treating HFpEF.The main pathogenesis of pre-heart failure is lung qi dysfunction-induced water retention,which can be treated by dispersing lung qi and transforming water retention using Fuling Xingren Gancao Decoction.The primary pathogenesis of symptomatic heart failure is yang and qi deficiency-induced water retention,which can be treated with tonifying yang,supplementing qi,and transforming water retention using Shengxian Decoction combined with Linggui Zhugan Decoction.The primary pathogenesis of advanced heart failure is yang deficiency with blood stasis and water retention affecting the heart,which can be treated with tonifying yang,circulating blood,and expelling water retention using Zhenwu Tingli Decoction.Chinese medicine can be flexibly added or subtracted according to the patients'concurrent patterns.However,the daily care of patients should be considered.This study explores the staging treatment of HFpEF from water,deficiency and blood stasis to provide a TCM clinical reference for treating HFpEF.

Objective To investigate the correlation between the expression of circulating exosome miR-485-3p and STYX with the risk of premature coronary heart disease.Methods A total of 50 inpatients with early onset coronary heart disease diagnosed by coronary angiography or CT angiography (CTA) in Af-filiated Puyang Municipal People's Hospital of Xinxiang Medical College from August to December 2023 were selected as the study group and 50 patients with excluded coronary artery disease by examination during the same period were included in the control group.The general clinical data of the two groups were collected,the plasma exosome miR-485-3p and STYX levels were detected.The degree of coronary arterial lesions in the pa-tients of the study group was evaluated by the Gensini score.The Spearman correlation analysis was used to analyze the relationship between plasma exosome miR-485-3p and STYX with LDL and Gensini score.The re-ceiver operating characteristic (ROC) curve was used to analyze the diagnostic value of plasma exosome miR-485-3p and STYX in the diagnosis of premature coronary heart disease.The multivariate logistic regression was used to determine the independent risk factors for premature coronary heart disease.Results Compared with the control group,the family history of coronary heart disease,smoking history,LDL and plasma exo-some miR-485-3p level in the study group were increased,the plasma STYX level was decreased and the differences were statistically significant (P<0.05);the Spearman correlation analysis showed that miR-485-3p was positively correlated with LDL (r=0.546) and Gensini score (r=0.485),and negatively correlated with STYX (r=-0.576).STYX was negatively correlated with LDL (r=-0.389) and Gensini score (r=-0.531).The ROC curve showed that the area under the curve of miR-485-3p,STYX and their combination in the diagnosis of premature coronary heart disease was 0.821 (95％CI:0.736-0.906),0.850 (95％CI:0.772-0.927) and 0.899 (95％CI:0.837-0.960) respectively.Conclusion The expression of circulating exosome miR-485-3p in premature coronary heart disease is up-regulated and the expression of STYX is down-regulated,the both are closely related to the degree of coronary artery lesion,which could be used as the po-tential biomarkers for the diagnosis of premature coronary heart disease.

Objective:To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas.Methods:This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results:After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [ M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group ( P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups( P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions:PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.