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.

Objective To evaluate the safety and effectiveness of endoscopic mucosal resection with circumferential incision(EMR-CI)and endoscopic submucosal dissection(ESD)for the rectal neuroendocrine neoplasm(RNEN).Methods Databases such as PubMed,the Cochrane Library,Embase,Web of Science,SinoMed,China National Knowledge Infrastructure(CNKI),Wanfang Data and Weipu database were searched by computer.The retrieval time limit was Nov.22,2022.The Chinese and English literatures on the efficacy of EMR-CI vs ESD in treatment of RNEN patients were collected.According to inclusion and exclusion criteria,the included literatures were screened,extracted data,and evaluated the methodological quality by Newcastle-Ottawa scale(NOS),Meta-analysis was performed using Rev Man 5.3 software.Results Seven clinical control studies were included,including 199 cases in the EMR-CI group and 443 cases in the ESD group.Results of Meta-analysis of validity outcome indicators,there was no significant difference in histological complete resection rate between the EMR-CI group and the ESD group(O(R) = 0.56,95%CI:0.30～1.02,P = 0.060);The endosopic complete resection rate of EMR-CI was similar to that of ESD with no significant difference(O(R) = 0.33,95%CI:0.09～1.17,P = 0.090);The size of lesions removed by EMR-CI was smaller than that of ESD with significant difference(WMD =-0.86,95%CI:-1.33～-0.40,P = 0.000);The time EMR-CI required to remove the lesion was significantly shorter than that of ESD(WMD =-12.48,95%CI:-16.42～-8.54,P = 0.000).The positive rate of horizontal resection margin of EMR-CI was similar to that of ESD,with no significant difference(O(R) = 1.74,95%CI:0.64～4.75,P = 0.280);The positive rate of vertical resection margin was significantly higher than that of ESD(O(R) = 2.41,95%CI:1.09～5.32,P = 0.030).Due to the low local recurrence rate and distant metastasis rate,Meta-analysis couldn't be compared.Safety outcome index showed that,there were no significant differences in the incidence of total complications,bleeding and perforation among groups.Conclusion In the treatment of RNEN,EMR-CI can achieve the endosopic complete resection,histological complete resection and positive rate of horizontal resection margin similar to ESD without increasing surgical complications and significantly saving surgical time.However,attention should be paid to the differences between EMR-CI and ESD in positive rate of vertical resection margin.

Objective To explore the value of dynamic prediction model based on recurrent neural network(RNN)algorithms for dynamic prediction of clinical outcomes in patients with critical trauma,and to study the feasible construction scheme and path of dynamic strategy and real-time prediction model.Methods The data of this study were derived from the US Medical Information Mart for Intensive Care(MIMIC)-IV 2.0.In order to predict the in-hospital outcomes of critical trauma patients,2 RNN algorithms,long short-term memory(LSTM)and gated recurrent unit(GRU)were used to train dynamic prediction models under the time windows of 4,6 and 8 h,respectively.The performance of the models was evaluated using the sensitivity,specificity,F1 value and area under curve(AUC)value;and the effects of different RNN algorithms and time windows on the performance of the models were analyzed.Hidden Markov model(HMM),random forest(RF)model and logistic model were trained under 8-h time window as the controls to compare the performances and the time trends horizontally with the 2 RNN algorithm models.Results There were significant differences in the 4 performance indexes of the RNN dynamic models including the sensitivity,specificity,F1 value and AUC value(all P＜0.001),and the performance indexes at 8-h time window were higher than those at 6 h and 4 h;there was only significant difference in specificity between different RNN algorithms(LSTM & GRU)(P=0.036).The results of the horizontal comparison showed that there were significant differences in each performance index between the 2 RNN prediction models and other models(all P＜0.001),and each index of the 2 RNN algorithm models was higher than those of the HMM,RF model and logistic model.The intraclass correlation coefficients(ICCs)of each algorithmic model were less than 0.400 for the sensitivity,specificity and F1 value(0 was not included in 95％confidence interval[CI]),while the ICCs for the AUC value were statistically under-evidenced(0 was included in 95％CI).Conclusion The dynamic models based on RNN algorithms have certain performance advantages over those based on other common algorithms,and the time window may have an impact on the model performance.

Objective To evaluate the application value of artificial intelligence mixed reality(AI-MR)technology in the planning of ultrasound-guided percutaneous nephrolithotomy(PCNL)for special types of complex upper urinary stones.Methods The prospective single-center,single-arm clinical study involved 15 patients with complex upper urinary stones undergoing ultrasound-guided PCNL during Aug.2022 and May 2023,including 9 male and 6 female,3 cases of pelvic ectopic kidney stones,5 cases of horseshoe kidney stones,3 cases of renal stones combined with spinal deformity,and 4 cases of transplant kidney stones.Based on preoperative computed tomography urography(CTU)data,digital three-dimensional reconstruction was performed,and AI-MR was used to project surgery-related three-dimensional images in real space to obtain"perspective"information of the surgical area.This facilitated preoperative design and planning,including target calyx,number of channels,and auxiliary measures.The compliance of target calyx and number of channels,stone clearance rate,total operation time,time required to establish the percutaneous renal channel,decrease in hemoglobin level,surgical complications,and postoperative hospital stay were analyzed.Results All 15 patients underwent preoperative planning using AI-MR and successfully completed one-stage ultrasound-guided PCNL.Based on the preoperative planning,we utilized S-PCNL alone or combined with Needle-perc or antegrade/retrograde FURS/RIRS.Among all patients,4 underwent single-channel S-PCNL,3 multi-channel S-PCNL,and 8 S-PCNL combined with Needle-perc or FURS.The compliance of target calyx and number of channels was 86.7％,the one-stage stone clearance rate was 80.0％,the average time for establishing the channel was(2.3±0.3)minutes,the average total operation time was(61.5±12.2)minutes,the mean decrease in hemoglobin level was(9.6±1.2)g/L,and the average postoperative hospital stay was(4.6±0.5)days.There were no Clavien-Dindo grade ≥ Ⅱ complications,such as blood transfusion,organ injury,or urosepsis.Conclusion Before surgery,AI-MR can be used to quantitatively analyze imaging data for patients with special types of complex upper urinary stones,which can achieve three-dimensional fluoroscopy effects,formulate surgical plans,optimize puncture paths,effectively avoid the risk of damage to surrounding organs,reduce complications,shorten treatment cycle and improve the first-stage stone clearance rate.

BACKGROUND:Increasing studies have shown that autophagy plays an important role in the treatment of osteoarthritis,and moderate autophagy can preserve the normal physiological function of osteoarticular chondrocytes.Traditional Chinese medicine(TCM)monomers can target and modulate autophagy to treat osteoarthritis,and their characteristics such as single components,clear efficacy,low price,and easy availability have obvious benefits in the treatment of osteoarthritis.OBJECTIVE:To review the effects of TCM monomers on the targeted regulation of autophagy in the treatment of osteoarthritis and the research progress,with a view to laying a foundation for the treatment of osteoarthritis and even other bone metabolic diseases.METHODS:Relevant literature published from January 2012 to October 2022 was retrieved in PubMed,Web of Science,CNKI,and WanFang using the keywords of"traditional Chinese medicine,Chinese herbal monomer,autophagy,osteoarthritis"in English and Chinese.Inclusion and exclusion criteria were developed,and 63 relevant articles were finally included by screening through reading the title,abstract,and full-text content.RESULTS AND CONCLUSION:TCM monomers can treat osteoarthritis by targeting autophagy to inhibit chondrocyte apoptosis,protect cartilage extracellular matrix,reduce inflammation and antagonize oxidative stress injury.Different TCM monomers can regulate autophagy in the same way,and the same TCM monomers can affect autophagy in different ways.The combination of multiple monomers and the multi-target and multi-pathway regulation of autophagy by TCM monomers remain to be explored.The regulation of autophagy by TCM monomers can provide new ideas and strategies for the prevention and treatment of osteoarthritis.Moderate regulation of autophagy by TCM monomers to keep the autophagic flux unimpeded may be the key to treating osteoarthritis.

BACKGROUND:More and more studies have shown that oxidative stress should play an important role in the treatment of osteoporosis.Oxidative stress should cause the accumulation of oxidation activity,which will damage bone-related cells.Finally,it causes the imbalance of bone resorption and bone formation,resulting in a decrease in bone volume and the destruction of the slight structure.Research in recent years has found that some natural products can regulate oxidative stress to treat osteoporosis.The characteristics of extensive sources and small side effects have obvious advantages in the treatment of osteoporosis,and the efficacy is objective. OBJECTIVE:To discuss the mechanism of natural product regulation of oxidation stress in treatment of osteoporosis,conduct a review based on the latest related research progress,provide reference and ideas for more natural products to treat osteoporosis in the future,and provide data support for the clinical application of natural compounds in the treatment of osteoporosis. METHODS:"oxidative stress,free radical,antioxidant,phytotherapy,plant extracts,medicinal plants,herbal medicine,osteoporosis,bone density,bone loss"were used as the keywords in PubMed,Web of Science,Embase,Cochrane,VIP,CBM,WanFang,and CNKI databases to search relevant articles published from January 2010 to February 2023.Inclusion and exclusion criteria were developed,and 64 relevant articles were selected by reading titles,abstracts,and full texts. RESULTS AND CONCLUSION:(1)Some natural products have antioxidant effects and can regulate osteogenic differentiation,osteoblast bone matrix mineralization,osteoclast-mediated bone resorption,proliferation,differentiation,activity,and apoptosis of bone-related cells by improving oxidative stress,thus affecting bone metabolism.(2)These natural products with antioxidant effects play a role in treating osteoporosis by improving bone remodeling balance.(3)The research on the combination of a variety of natural products to improve osteoporosis remains to be explored.(4)The use of natural products to regulate oxidative stress may become a powerful weapon for the clinical treatment of osteoporosis in the future.

Objective:To investigate of the concentrations of uranium in drinking water in Inner Mongolia Autonomous Region for providing theoretical basis for the health protection of local residents and the assessment of nuclear emergency.Methods:During the dry season and wet water season, tap water and well water samples were collected from 12 cities in Inner Mongolia, 644 unfiltered water samples and 34 filtered water samples were collected, and the uranium concentrations in drinking water was measured using a trace uranium analyzer.Results:During dry and wet seasons the uranium concentration were 0.85-23.61 μg/L and 0.98-23.65 μg/L in tap water, 3.74-88.28 μg/L and 3.68-95.36 μg/L in well water, respectively.Conclusions:The levels of uranium concentrations in drinking water in Inner Mongolia has been preliminarily ascertained, and the installation of filtration devices can significantly reduce the content of uranium in drinking water.

Objective To establish a quantitative polymerase chain reaction(PCR)method for the analysis of human-derived SRY DNA in mouse tissues,and to study the tissue distribution of human umbilical cord mesenchymal stem cells(HUCMSCs)in immunodeficient NOG mice after a single intravenous injection.Methods We established a quantitative PCR method for the analysis of human SRY DNA in mouse tissues,and validated the standard curve,linear range,accuracy,precision,and stability.Thirty-six NOG mice(18 male,18 female)were administered 3.5×107 HUCMSCs/kg by single intravenous injection.Six mice were then anesthetized and dissected after blood collection(EDTA anticoagulation)at 6,12,24,and 72 h,and at 1 and 2 weeks,respectively.DNA was extracted from lung,kidney,heart,liver,brain,spinal cord,stomach,small intestine,fat,skin,spleen,testis,uterus,and ovary tissues,and the distribution of HUCMSCs in each tissue was determined by the validated quantitative PCR method for detecting the human-derived SRY gene in mouse tissues.In addition,18 NOG mice(9 male,9 female)were divided into control(n = 6)and treatment groups(n = 12)injected intravenously with 0.9%sodium chloride and 3.5×107 cells/kg,respectively.Acute toxic reactions were observed during the administration period,and four animals were dissected at 72 h and at 2 and 4 weeks after administration to observe the gross organs.Mitochondrial protein expression was detected in paraffin sections of lung tissues by immunohistochemistry to analyze the colonization of HUCMSCs in lung tissues.Results The established RT-qPCR method for human-derived SRY DNA in mouse tissues met the validation criteria for each index.After a single intravenous injection in NOG mice,HUCMSCs were mainly distributed in the lungs and blood within 1 week after administration,with higher concentrations in lung tissues than in blood.The concentrations of HUCMSCs in lung tissue and blood remained relatively stable within 6～24 h and 6～72 h,respectively,and then decreased over time.The distribution of HUCMSCs in other tissues was not measured at all sampling points.The colonization result showed that HUCMSCs were detected in lungs 72 h after intravenous injection,but not at 2 and 4 weeks.No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs.Conclusions The above method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible.HUCMSCs were mainly distributed in lung and blood in NOG mice within 1 week after a single intravenous injection,and mainly colonized lung tissue at 72 h.A single intravenous administration of HUCMSCs has a good safety profile.

Osteoporosis， a common metabolic bone disease， is caused by the imbalance of bone homeostasis. Bone homeostasis depends on the dynamic balance between bone resorption by osteoclasts and bone matrix formation by mesenchymal lineage osteoblasts and involves a series of complex and highly regulated steps. When bone resorption is faster than bone formation， bone homeostasis will be destroyed， which will lead to osteoporosis. Autophagy is a protein and organelle degradation pathway important for the maintenance of cytoplasmic homeostasis. The basal level of autophagy is present in all the three types of bone cells. Autophagy is a process whereby damaged organelles are recycled and bone remodeling continues， and thus it plays an important role in bone maintenance. Therefore， it is possible to regulate bone metabolism by targeting specific autophagy-related molecules. At the same time， as the research on the treatment of osteoporosis by Chinese medicine advances， it is found that the monomers isolated from traditional Chinese medicinals have the potential of regulating autophagy in the treatment of osteoporosis. Thus， this paper discusses the relationship between autophagy and osteoporosis and summarizes six different mechanisms of 22 Chinese medicine monomers in the treatment of osteoporosis through targeting autophagy： increasing osteogenic differentiation of mesenchymal stem cells， promoting osteoblast mineralization， inhibiting osteoclasts differentiation， reducing apoptosis of bone cells， antagonizing oxidative stress injury， and coordinating inflammation and autophagy levels. The review is expected to provide a reference and ideas for future research on the treatment of osteoporosis by Chinese medicine monomers.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.