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.

BACKGROUND:Magnetic nanomaterials have biological activities such as promoting osteogenic differentiation of stem cells and inhibiting osteoclast formation,and can effectively promote the healing of injured bone tissue under the synergistic effect of magnetic fields.They have a very broad application prospect in bone injury repair. OBJECTIVE:To review the mechanism of magnetic nanomaterials and magnetic fields promoting bone repair,as well as their research progress in the field of bone injury repair. METHODS:Relevant literature search was conducted in PubMed and Web of Science databases with the search terms"magnetic nanomaterials,magnetic field,bone repair,bone tissue engineering,stem cell,osteoblast,osteoclast."The time limit of literature search was from 2003 to 2023,which was screened and analyzed.Some classic articles were manually retrieved,and 98 articles were finally included for analysis. RESULTS AND CONCLUSION:(1)Magnetic nanomaterials have biological effects such as promoting osteoblast differentiation,inhibiting osteoclast formation and regulating the immune microenvironment.In addition,magnetic nanomaterials can regulate the physicochemical properties of tissue engineering scaffolds,such as mechanical properties and surface morphology,and endowed with magnetic properties,which is conducive to the regulation of the adhesion,proliferation and osteogenic differentiation of stem cells.(2)The magnetic field has the ability to regulate multiple cell signaling pathways to promote osteoblast differentiation,inhibit osteoclast formation,stimulate angiogenesis and other biological effects,thus accelerating the healing of damaged bone tissue.(3)The joint application of magnetic nanomaterials and magnetic field accelerates the repair of bone damage by activating mechanotransduction,increasing the content of intracellular magnetic nanoparticles,and enhancing the effect of micro-magnetic field,which provides a new idea for the research of bone tissue engineering.(4)Magnetic field has demonstrated definite efficacy in the treatment of clinical fractures,osteoporosis,and osteoarthritis diseases,which is beneficial for bone tissue growth,reducing bone loss,alleviating pain,and improving the quality of life of patients.(5)Magnetic nanomaterials and magnetic fields have great potential for application in bone damage repair and regeneration,but the interaction mechanism between magnetic nanomaterials,magnetic fields,and cells has not been fully elucidated.Moreover,the key parameters of magnetic fields that regulate intracellular molecular events,including the type,intensity,frequency,duration,and mode of the magnetic field,as well as the precise biological effects of a specific magnetic field on osteoblasts and the underlying mechanisms,have yet to be defined.(6)Further attention needs to be paid to the effects on osteoclasts,nerves,blood vessels,and immune cells in the microenvironment of damaged tissues.Finally,the safety of magnetic materials for human use is yet to be systematically studied in terms of their distribution,metabolism,and acute and chronic toxicities.

OBJECTIVE: To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVES: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression. METHODS: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression. RESULTS: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania. CONCLUSIONS This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans ; Bipolar Disorder/drug therapy* ; Vortioxetine/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Valproic Acid/administration & dosage* ; Lurasidone Hydrochloride/administration & dosage* ; Prospective Studies ; Treatment Outcome ; Pilot Projects ; Drug Therapy, Combination ; Sulfides/therapeutic use* ; Antidepressive Agents/therapeutic use*

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.