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 Jejunal interposition is an important option for restoring gastrointestinal continuity in patients with complex esophageal cancer in whom the stomach is unavailable for reconstruction due to previous gastrectomy, tumor involvement, failed gastric conduit, or other constraints. Although the jejunum offers a caliber similar to the esophagus, a rich blood supply, and preserved peristaltic function, anatomical variations in mesenteric length and vascular arcades render long-segment and high-level reconstruction susceptible to excessive tension, mesenteric torsion, venous congestion, and inadequate distal perfusion. This consensus aims to provide standardized recommendations for the application of jejunal interposition in this specific patient population. Methods This consensus was developed in accordance with the WHO Handbook for Guideline Development and Chinese national guideline development standards, with reference to the Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ), Reporting Items for Practice Guidelines in Healthcare (RIGHT), and Scientific, Transparent and Applicable Rankings (STAR) checklists. The project was registered on the international practice guidelines registry platform (PREPARE-2026CN1384). The working group systematically searched Chinese and English evidence addressing 12 clinical questions. Evidence was graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 system, with structured appraisal of risk of bias, inconsistency, indirectness, and imprecision. Recommendations were formulated through two rounds of Delphi surveys and a face-to-face consensus meeting, with an agreement threshold of ≥75%. Results The consensus generated 12 recommendations covering indications, selection between jejunum and colon, preoperative assessment, surgical approach and reconstruction route, pedicled jejunal interposition (PJI), supercharged pedicled jejunal interposition (SPJ), indocyanine green (ICG) perfusion assessment, perioperative nutrition, management of anastomotic leakage, long-term follow-up, and special treatment scenarios. Given that the available direct evidence is predominantly derived from single-center retrospective cohorts and case series, recommendations extrapolated from general esophagectomy or other gastrointestinal surgical evidence are deliberately phrased with caution. Conclusion Jejunal interposition is a safe and effective approach for digestive tract reconstruction in patients with complex esophageal cancer in whom the stomach is unavailable. This consensus emphasizes that clinical decision-making should be individualized based on the patient's prior treatment history, reconstruction height, vascular anatomy, technical availability, and institutional experience in the Chinese context.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Objective To determine the median effective dose(ED50)of remimazolam for preoperative sedation in pediatric patients aged 1-6 years using the modified Dixon sequential method.Methods This is a prospective clinical study.Pediatric patients scheduled for elective short surgery(surgery time≤1 h)under general anesthesia from January to July 2023 were selected.Inclusion criteria were age 1-6 years,an ASA physical status Ⅰ-Ⅱ and the preoperative parent separation anxiety scale(PSAS)score≥3 points.Remimazolam was administered intravenously preoperatively,and its sedative effect was assessed.The modified Dixon sequential method was used to determine the ED50 of remimazolam,with the initial dose set at 0.10 mg/kg and the dose increment set at 0.02 mg/kg.Sedation was considered successful(positive,included in positive group)if the child with sedation score≥2 points,preoperative PSAS score<3 points,and the mask acceptance score of 4 points during anesthesia induction.If any criterion was not met,sedation was considered failure(negative,included in negative group),and the next patient's dosage was increased by 0.02 mg/kg based on the previous patient's dosage.The test was completed after 7 consecutive positive and negative turning points appeared alternately.Probabilistic unit regression analysis was used to determine the ED50,ED95 and the corresponding 95%confidence interval(CI)of remimazolam for preoperative sedation.Postoperative recovery time and adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting during anesthesia were recorded.Results A total of 23 pediatric patients were included,with 13 in positive group and 10 in negative group.There were no statistically significant differences in mean arterial pressure,pulse oxygen saturation or heart rate before and after sedation(P>0.05).Compared with negative group,positive group showed a significant reduction in preoperative parent separation anxiety and an increase in mask acceptance during anesthesia(P<0.05).There was no significant difference in sedation score and anesthesia awakening time between two groups(P>0.05).The ED50 of remimazolam for preoperative sedation in pediatric patients aged 1-6 years was 0.051 mg/kg(95%CI 0.033-0.065 mg/kg),and the ED95 was 0.077 mg/kg(95%CI 0.064-0.161 mg/kg).No adverse events such as airway spasm,respiratory depression,hypotension,nausea and vomiting occurred during anesthesia in any of pediatric patients.Conclusion The ED50 of intravenous administration of remimazolam for preoperative sedation in pediatric patients aged 1-6 years is 0.051 mg/kg(95%CI 0.033-0.065 mg/kg).

Objective To explore the spatiotemporal expression patterns of Patched 1(Ptch1)and insulin enhancer binding protein-1(Isl 1)in mouse embryonic foregut and their relationship with the early development of trachea-main bronchus.Methods The foregut of 60 mouse embryos at E9.5-12.5 was separated for the detection of Isl1 and sonic hedgehog(Shh)protein by Western blotting.Serial paraffin sections of 6 mouse embryos at E9.5-14.5 were taken for immunohistochemical staining and immunofluorescence double staining with Isl1,Ptch1,forkhead box protein A2(Foxa2),type Ⅱ collagen α1 chain(Col2a1)and α-smooth muscle actin(α-SMA),as well as HE staining and Masson staining.Results The expression trend of Isl1 and Shh in foregut endoderm at E9.5-12.5 was similar,and the peak of Shh expression was later than Isl1.The foregut developed into the trachea at E9.5-12.5,Ptch1 was expressed in the thickening and protrusion of the respiratory endoderm,the laryngal-tracheal groove and the solid cell cord,accompanied by the increase and aggregation of Isl1-positive mesenchymal cells,forming a characteristic pyramidal structure centered on the respiratory endoderm and the solid cell cord;The main bronchus appeared at E12.5-13.5,Ptch1 was only expressed in its lateral wall,accompanied by the accumulation of Isl1-positive mesenchymal cells;The trachea-main bronchial epithelium lost Ptch1 expression and the surrounding Isl 1-positive mesenchymal cells also decreased rapidly at E13.5-14.5.Co12a1-positive chondrocytes first appeared in the Isl1-positive mesenchymal area adjacent to the Ptch1-positive epithelium at E12.5;Col2a1-positive cartilage was nested within the Isl1-positive mesenchymic area in a"C"shape and expanded in a proximal-distal pattern at E12.5-13.5;Col2a1-positive cartilage extended to the dorsal trachea beyond the Isl1-positive mesenchyma and encircles α-SMA positive smooth muscle in a circular manner at E14.5.Conclusion The expression of Ptch1 in the foregut endoderm is involved in the development and morphogenesis of the trachea-main bronchus epithelium,and is closely related to the proliferation and aggregation of Isl1-positive mesenchyme in the trachea-main bronchial wall,Subsequently,they jointly determine the time,location and extent of airway cartilage.

ObjectiveTo explore the effects of the Tai Chi training on bone density， bone turnover markers， and heart rate variability for people with high-risk osteoporosis， and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included， and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week， and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group， and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L₁~L₄ vertebrae， bilateral femoral necks and bilateral total hips in the two groups before and after the intervention； enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention， including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide （P1NP） and β-collagen type Ⅰ cross-linking carboxy-terminal peptide （β-CTX）. Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor， they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each， and the heart rate variability （HRV） during exercise was collected， including time-domain indexes such as standard deviation of normal sinus intervals （SDNN）， root-mean-square of the difference between adjacent RR intervals （RMSSD）， frequency-domain metrics such as low-frequency power （LF）， high-frequency power （HF）， and low-frequency/high-frequency power ratio （LF/HF）， as well as nonlinear metrics such as approximate entropy （ApEn）， sample entropy （SampEn）. ResultsFinally， 63 cases were included in the outcome analysis， including 30 cases in the intervention group and 33 cases in the control group. After the intervention， the differences of L₁~L₄ vertebrae， bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention （P＞0.05）， while the bone density of all parts of the control group decreased significantly compared with that before intervention （P＜0.05）， and the difference in the bone density of the L₁~L₄ vertebrae， bilateral femoral neck， and the right total hip before and after the intervention of the intervention group was smaller than that of the control group （P＜0.05）. The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant （P＞0.05）. Compared with walking exercise， LF decreased， HF increased and LF/HF decreased during Tai Chi exercise （P＜0.05）； the time domain indexes and non-linear indexes between groups had no statistically significant difference （P＞0.05）. ConclusionTai Chi exercise can maintain lumbar， hip， and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis， but cannot significantly improve bone turnover markers.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.