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.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Chagas disease(American trypanosomiasis)is a zoonosis caused by Trypanosoma cruzi,which severely affects public health.Recently,with changes in economic globalization and increased population mobility,this disease has gradually spread from the original Latin American epidemic areas to non-epidemic areas,such as Europe,thus showing a trend of globalization.The main trans-mission routes have changed from transmission via the Triatomine vector to blood transfusion transmission,mother-to-child transmis-sion,oral transmission,and other routes.Consequently,Chagas disease is spreading globally,and more people are increasingly vul-nerable to infection.This article retrospectively reviews research on the transmission routes of Chagas disease,analyzes the changing trends in transmission routes,and provides a scientific basis for the formulation and optimization of Chagas disease prevention and con-trol strategies from a One Health perspective.

Objective:To study echinococcosis in the population and canine Echinococcus infection in Yushu City, Qinghai Province, and to explore the current epidemic situation and main transmission species of Echinococcus. Methods:In June 2023, a multi-stage sampling method was used to select 2 villages each in Shanglaxiu Township and Longbao Town, Yushu City, Qinghai Province. Each village included at least 100 permanent residents who had lived locally for at least 1 year and were 2 years old or older as the survey subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum antibodies against Echinococcus larvae in the population, and B-mode ultrasound was used for abdominal organ scanning. Meanwhile, on the main roads of Shanglaxiu Township and Longbao Town, canine feces were collected in designated areas at intervals. ELISA was used to detect the antigen of canine fecal Echinococcus, and PCR was used to detect the types of parasites ( Echinococcus multilocularis, Echinococcus granulosus and Echinococcus shiquicus). Results:A total of 511 residents were investigated in Yushu City, and the positive rate of serum Echinococcus larvae antibodies in the population was 26.22% (134/511), and the detection rate of echinococcosis B-mode ultrasound was 1.37% (7/511). Among them, the detection rates of B-mode ultrasound for cystic echinococcosis (CE) and alveolar echinococcosis (AE) were 1.17% (6/511) and 0.20% (1/511), respectively. The positive rate of Echinococcus antigen in 543 canine feces detected by ELISA was 12.89% (70/543). PCR was used to test 497 canine feces, and the detection rate of Echinococcus was 3.02% (15/497). Among them, the detection rate of Echinococcus multilocularis was higher than that of Echinococcus granulosus [2.82% (14/497) vs 0.20% (1/497)], and the difference was statistically significant (χ 2 = 11.44, P < 0.001). No Echinococcus shiquicus was detected. Conclusions:The positive rates of Echinococcus larvae antibodies in the population and canine Echinococcus antigen in Yushu City, Qinghai Province are both relatively high. There is a mixed epidemic of CE and AE, with Echinococcus multilocularis being the main species.

To perform the phylogenetic characterization of an isolated porcine rotavirus(PoRV)and investigate its pathogenicity in suckling mice and piglets.A G4P[23]genotype PoRV strain JSJR2023 was successfully isolated from the diarrheic piglet feces through propagation in MA104 cells.The viral proliferation kinetics were analyzed using TCID50 assays,followed by complete genome sequencing through Sanger sequencing platforms.Comprehensive genotyping and phylogenetic reconstruction were conducted using MEGA7.0 with maximum likelihood algorithms.Pathogenicity was assessed in the following animal models:5-day-old C57BL/6 mice and 3-day-old piglets.Multidimensional evaluation included clinical monitoring(diarrhea scoring,growth parameters),virological detection,and histopathological analysis of intestinal tissues.The virus strain JSJR2023 could replicate efficiently in MA104 cells,achieving peak titers of 107.5 TCID50/mL.Whole genome genotype analysis showed that the strain belonged to G4-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1.Phylogenetic analysis indicated that the VP3 and NSP4 genes of JSJR2023 strain were most closedrelated to human species rotaviruses,suggesting genetic reassortment between human and porcine RV strains.The animal experiments in suckling mice showed that the JSJR2023 strain infection caused diarrhea symptoms,intestinal edema and congestion,and shedding of intestinal villus epithelial cells.The pathogenicity experiments in piglets showed that compared with the control group,the challenged group of pig-lets had severe diarrhea symptoms,accompanied by reduced appetite and listlessness.Post-mortem examination revealed that the intes-tines were significantly thinner,congested,and filled with yellow watery contents.The challenged piglets showed typical pathological changes such as thinning of the intestinal wall and shortening and shedding of intestinal villi.In conclusion,this study successfully iso-lated a human-porcine recombinant G4P[23]PoRV strain and established the infection models in suckling mice and piglets,providing important tools for investigating the pathogenic mechanism of PoRV,evaluating vaccines and developing antiviral drug.

Barrett's esophagus(BE),a precancerous state of esophageal adenocarcinoma,poses a major challenge for prevention and treatment owing to its complex mechanism of inflammation-cancer transformation and the lack of effective clinical treatment and torsion strategies.Building upon the"preventing disease progression"theory,this study aimed to address the critical clinical challenge of intercepting the pathological progression during the inflammation-cancer transformation of BE by proposing an innovative"two critical nodes-three stages"pathomechanism framework.The pathogenesis of BE originates from liver depression and qi stagnation.The pathological progression evolves through two critical nodes:liver depression transforming into heat and heat transforming into blood stasis,representing a three-stage evolutionary pattern of qi stagnation,heat transformation,and blood stasis formation.Acidic bile salts,acting as a pathogenic toxin,permeate the entire process and catalyze carcinogenesis.Based on this understanding,the therapeutic principles of"treatment from the liver"and"truncation and torsion"were established,emphasizing stage-specific interventions.For the qi stagnation stage,treatment focuses on soothing the liver and regulating qi,as well as moistening,harmonizing,and descending the qi.This is achieved by combining modified Chaihu Shugan Powder with Xuanfu Daizhe Decoction,while using pungent and drying herbs cautiously and supplementing them with light and floral herbs.In the heat transformation stage,the strategy aims to clear the liver and drain heat while protecting yin and harmonizing the stomach,employing modified Huaganjian combined with Yiguanjian and supplemented with Jinlingzi Powder to clear depressed fire.For the blood stasis formation stage,treatment involves activating blood and resolving stasis,combined with supporting healthy qi and removing toxins.This is achieved using a modified Gexia Zhuyu Decoction,supplemented with Liujunzi Decoction,and additions such as Radix Salviae Miltiorrhizae and turtle carapace to disperse nodules and reduce masses.This theoretical framework establishes a diagnostic and therapeutic model characterized by the integration of disease mechanisms with pathology and the mutual reference of macro-level signs with micro-level indicators.It provides a comprehensive clinical practice pathway,complete with principles,methods,formulas,and herbs,for the stage-specific interception of inflammation-cancer transformation in BE using traditional Chinese medicine.