Functional constipation （FC） is a clinically common functional bowel disorder characterized by a protracted course and associations with various chronic disorders and psychological abnormalities. Although not life-threatening， FC significantly impairs patients' quality of life. FC subtypes include slow-transit constipation （STC）， defecatory disorder （DD）， and normal-transit constipation （NTC）. The pathological mechanisms underlying FC have not been fully elucidated， and overall clinical efficacy remains unsatisfactory. Animal models of FC serve as essential tools for the study of disease mechanisms and the development of novel therapeutics. This article systematically reviews the current state of research on the animal models of FC and identifies that rodents， particularly rats and mice， are the most commonly used species. Dogs and pigs are also employed in complex intervention studies due to their physiological similarities to humans， though their use is limited by housing challenges and ethical considerations. Induction methods vary across different FC subtypes. STC models are primarily established with chemical agents such as loperamide or compound diphenoxylate. DD modeling often involves low-fiber diets combined with methylene blue injection or rectal narrowing. NTC modeling mainly relies on low-fiber dietary interventions. In addition， disease-syndrome combination models based on traditional Chinese medicine （TCM） theory have been developed， encompassing excess patterns such as heat accumulation， cold accumulation， and Qi stagnation， as well as deficiency patterns including Qi deficiency， blood deficiency， Yin deficiency， and Yang deficiency. These are achieved through an approach of disease model + syndrome induction， enabling the integration of mechanisms from both Western and TCM perspectives. Models are evaluated from two aspects： disease and syndrome manifestations （e.g.， colonic transit， secretory function， and TCM syndrome indicators such as mental state and body weight） and disease mechanisms （e.g.， enteric nervous system， interstitial cells of Cajal， smooth muscle cells， gut microbiota， and metabolites）. However， current research still faces challenges such as poor consistency in some models， non-specific interference in mechanism interpretation， insufficient studies on NTC， and lack of TCM tongue and pulse diagnosis in evaluation. Future efforts should focus on optimizing model stability and specificity to provide a more reliable experimental basis for investigating the pathological mechanisms of FC and developing therapeutic agents.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.

Objective To explore the correlation of traditional Chinese medicine(TCM)syndrome elements with language function and activities of daily living(ADL)in patients suffering post-stroke aphasia(PSA).Methods Ninety-eight PSA patients hospitalized at the College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine from April 2023 to April 2024 were selected.The language function,TCM syndrome elements,and their correlations were analyzed.Results(1)Among PSA patients,males outnumbered females.PSA patients exhibited different performances on various aphasia-related scales,with language impairments mainly concentrated in naming and spontaneous speech.(2)The distribution of TCM syndrome elements varied in PSA patients with different age groups.In the age group＜50 years old,qi obstruction(100.00%),phlegm syndrome(100.00%),and dampness syndrome(100.00%)were predominant.In the age group of 50-59 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.30%)were predominant.In the age group of 60-69 years old,phlegm syndrome(100.00%)and yang hyperactivity syndrome(96.15%)were also predominant.In the age group of 70-79 years old,qi deficiency syndrome(100.00%)was predominant.In the age group of 80-89 years old,syndromes such as qi insecurity,qi obstruction,qi deficiency,phlegm,yang hyperactivity,blood stasis,wind stirring,and blood cold were concentrated(all 100.00%).However,there were no statistically significant differences in the distribution of TCM syndrome elements among various age groups(P＞0.05).(3)The distribution of deficiency and excess syndrome elements varied in PSA patients with different genders.Among deficiency syndrome elements,yang hyperactivity,qi deficiency,and yin deficiency were predominant in males,while yang hyperactivity,qi deficiency,and blood deficiency were predominant in females.Among excess syndrome elements,phlegm syndrome,qi obstruction,and dampness syndrome were predominant in males,while phlegm syndrome,qi obstruction,and qi stagnation syndrome were predominant in females.However,there were no statistically significant differences in the distribution of deficiency and excess syndrome elements between genders(P＞0.05).(4)After controlling the factors of age group and gender,partial correlation analysis of syndrome elements and language function showed that among the disease-location syndrome elements,spontaneous naming(r=-0.588,P=0.027)and sematic cued naming(r=-0.558,P=0.038)in the Boston Naming Test(BNT)were negatively correlated with the large intestine;among the disease-nature syndrome elements,BNT sematic cued naming(r=0.821,P＜0.001)was positively correlated with qi sinking,while BNT spontaneous naming was negatively correlated with blood heat(r=-0.544,P=0.044)and was positively correlated with fluid depletion(r=0.860,P=0.028);BNT recognitive naming was positively correlated with external wind(r=0.966,P=0.034);errors in BNT sematic cued naming were negatively correlated with qi sinking(r=-0.540,P=0.005);the Modified Barthel Index(MBI)was positively correlated with essence deficiency(r=0.572,P=0.021).Conclusion The TCM syndrome elements of phlegm,qi block,yang hyperactivity,and qi deficiency are commonly seen in PSA patients.There is a certain correlation of language function and ADL with TCM syndrome elements in PSA patients.

Spinal cord injury(SCI)is a central nervous system disease with high morbidity and disability rates,bringing serious economic and psychological burdens to families and society worldwide.AMP-activated protein kinase(AMPK)is an important sensor in the energy metabolism process in living organisms,which plays a central role in maintaining energy balance.It is currently considered a key target for the prevention and treatment of multiple diseases.Studies have shown that AMPK signaling can regulate autophagy,neuroinflammation,oxidative stress,mitochondrial function and other processes after SCI,thus affecting the pathological process of SCI.This review summarizes the research progress on AMPK signaling pathway involved in the regulation of SCI,in order to provide new ideas for the treatment and drug development of SCI.

Objective To explore the risk factors of venous thromboembolism(VTE)following laparoscopic urological surgery and to construct a predictive model.Methods A retrospective analysis was conducted on the clinical data from 846 laparoscopic surgery patients admitted to the Urology Department of Hainan Cancer Hospital from January 2020 to January 2023.Patients were divided into VTE group(n=64)and non-VTE group(n=782)based on postoperative VTE confirmed by imaging examination.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for VTE after laparoscopic urological surgery.A predictive model was developed using regression coefficients from the multivariate analysis,and its predictive accuracy was assessed using a nomogram.Additionally,its sensitivity and specificity were evaluated through the construction of a receiver operating characteristic(ROC)curve and a calibration curve.The clinical application of predictive model was evaluated using a decision curve analysis.Results The incidence of VTE after laparoscopic urological surgery was 7.6%(64/864).Significant differences were observed between two groups in age,body mass index(BMI),hypertension,diabetes,malignant tumor,history of abdominal surgery,previous VTE,operation time≥4 h,preoperative fibrinogen levels,preoperative prothrombin time,postoperative D-dimer(D-D)levels,Caprini score and postoperative immobilization time(P<0.05).Increasing age,higher BMI,history of malignancy,abdominal surgery,and previous VTE,longer operation and postoperative immobilization time,and higher postoperative D-D levels and Caprini score were identified as independent risk factors for the development of VTE after urological laparoscopy(P<0.05).Based on the regression coefficients between independent risk factors,a predictive model was constructed as P=ex/(1+ex),where X=0.054×age+0.105×BMI+0.902×history of abdominal surgery+1.172×previous VTE+0.787×operation time+1.546×malignant tumor+0.867×postoperative D-D+1.303×Caprini score+0.544×postoperative immobilization time-13.888.The model demonstrated a discriminant evaluation C-index of 0.827,and the area under the ROC curve for the combined independent risk factors is 0.827(95%CI 0.776-0.878),with a sensitivity of 64.1%,and specificity of 87.7%.Calibration and decision curves indicated that high predictive accuracy and clinical application of the model.Conclusions Increasing age,higher BMI,history of malignancy,abdominal surgery,and previous VTE,longer operation and postoperative immobilization time,and higher postoperative D-D and Caprini score are independent risk factors for the development of VTE after urological laparoscopy.

Objective To identify risk factors for severe hand-foot-mouth disease(HFMD)cases in Fuzhou,providing scientific evidence for disease prevention and control.Methods Severe pediatric HFMD cases in Fuzhou between 2017 and 2024 were collected from the"China Disease Prevention and Control Information System".Non-severe cases were frequency-matched based on the same onset period,same affected region,same parents'educational level,and age(±1 year)to form a non-severe group.Demographic characteristics,clinical symptoms,medical history,and pathogen types of both groups were collected.Logistic regression was used to identify the risk factors for severe cases.Results From 2017 to 2024,Fuzhou reported 503 severe HFMD cases and 1053 matched non-severe cases.Demographically,severe group had a higher proportion of home-based childcare,rural residence,care-seeking delay>2 d,while EV71 vaccination rates,handwashing habits before meals and after defecation,and caregivers with HFMD prevention education were lower than those in non-severe group,with statistically significant difference(P<0.001).Clinically,severe group showed more frequent fever>3 d,altered consciousness/seizure,limb tremors/convulsions,the proportion of infectious disease and the proportion of EV71-positive cases than those in non-severe group(P<0.001).Multivariate logistic regression analysis showed that home-based childcare(OR=3.213,95%CI 1.913-5.398),rural residence(OR=2.121,95%CI 1.513-2.973),lack of EV7 vaccination(OR=3.141,95%CI 1.996-4.945),care-seeking delay>2 d(OR=2.004,95%CI 1.410-2.849),no handwashing habits before meals and after defecation(OR=3.927,95%CI 1.718-5.356),caregiver without HFMD education(OR=2.465,95%CI 1.807-3.362),fever>3 d(OR=2.585,95%CI 1.801-3.709),altered consciousness/seizures(OR=4.059,95%CI 2.731-6.031),limb tremors/convulsions(OR=2.087,95%CI 1.398-3.117),history of infectious disease(OR=3.369,95%CI 1.725-6.335)and EV71 positivity(OR=3.854,95%CI 2.678-5.545)were risk factors for severe HFMD cases.The recovery time in severe group was significantly longer than that in non-severe group[18(5,32)d vs.11(4,23)d,P<0.001].Conclusions Prevention and control efforts should target high-risk groups by strengthening health education,promoting EV71 vaccination and improving the treatment of severe HFMD cases to reduce the incidence of severe HFMD.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans ; MEF2 Transcription Factors/physiology* ; Bone and Bones/metabolism* ; Animals ; Bone Development/physiology* ; Osteogenesis/physiology* ; Myogenic Regulatory Factors/physiology*

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*