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.

By reviewing modern research and integrating clinical practice， this paper interprets the correlation between "deep heat， deep syncope" and the "macrocirculation-microcirculation" uncoupling in sepsis， alongside its clinical applications in sepsis prevention and treatment. It is considered that "deep heat" corresponds to peripheral vasodilation and the hypermetabolic state at the macrocirculation level， whereas "deep syncope" manifests as hypoperfusion and impaired oxygen utilization at the microcirculation level. These two states interact detrimentally， forming the core contradiction of macrocirculation-microcirculation uncoupling in sepsis. Based on the traditional Chinese medicine （TCM） connotations of "deep heat， deep syncope" and modern medical research， this paper elucidates the systemic pathological evolution of sepsis from the inflammatory cascade to impaired oxygen utilization. Accordingly， the following therapeutic principles are proposed. In the early stage， it is suggested to clear heat and drain fire to vent the constrained yang. In the progressive stage， the focus is put on unblocking the lower jiao （焦） and expelling stasis to dredge the vessels and collaterals. In the recovery stage， the method of regulating and harmonizing yin and yang can be used to smooth the flow of qi and blood.

ObjectiveTo explore the possible mechanism of Jianpi Huazhuo Tiaozhi Granule （健脾化浊调脂颗粒， JHTG） in treating atherosclerosis （AS） based on the regulation of perivascular adipose tissue （PVAT） browning via the phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway. MethodsFifteen SPF male C57BL/6J mice served as control group， while 76 ApoE^-/- mice were first fed a high-fat diet for 16 weeks to establish AS model. After successful modeling， they were randomly divided into model group （n=16）， as well as the browning group， the low-， medium- and high-dose JHTG group， with 15 mice in each group. The browning group was intraperitoneally injected with β3-adrenergic receptor agonist CL 316243 at 1 mg/（kg·d） once daily. The low-， medium- and high-dose JHTG groups were treated with 4.3 g/（kg·d）， 8.6 g/（kg·d）， and 17.2 g/（kg·d） of JHTG by gavage， respectively， while the control group and the model group were given normal saline at 10 ml/（kg·d） by intragastric administration， once daily. All groups received continuous intervention for 4 weeks. The aorta was collected to assess the plaque ratio by gross oil red O staining. HE staining was used to measure the plaque area in cross-sections. Masson staining was employed to detect the proportion of collagen fibers in plaque. Transmission electron microscopy was used to observe the quantity and morphological changes of mitochondria and lipid droplets in adipocytes. The levels of serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected， as well as tumor necrosis factor α （TNF-α） and interleukin 6 （IL-6） levels in the PVAT and aorta. The protein levels of adiponectin and leptin in PVAT， and protein expression levels of phosphoinositide 3-kinase （PI3K）， phosphorylated phosphoinositide 3-kinase （p-PI3K）， protein kinase B （AKT）， phosphorylated protein kinase B （p-AKT）， uncoupling protein 1 （UCP1）， peroxisome proliferator-activated receptor γ coactivator 1α （PGC-1α）， and PR domain containing 16 （PRDM16） were measured. The mRNA expression levels of UCP1， PGC-1α and PRDM16 in PVAT were detected. ResultsCompared to the control group， the model group showed increased serum TG， TC， and LDL-C levels and decreased HDL-C level， elevated TNF-α and IL-6 levels in PVAT and aorta， decreased average fluorescence intensity of adiponectin， increased average fluorescence intensity of leptin， reduced p-PI3K/PI3K and p-AKT/AKT values as well as protein levels and mRNA expression levels of UCP1， PGC-1α and PRDM16 （P＜0.01）. The pathological results showed that no significant plaque formation was observed in the aortas of mice in the control group. In the model group， multiple plaques were observed in the aortas， with large numbers of foam cells， cholesterol crystals， and inflammatory cell aggregation in the plaques. Compared to the model group， the browning group and the high-dose JHTG group significantly improved the above indicators and aortic pathological changes （P＜0.05 or P＜0.01）. Three JHTG groups showed a dose-dependent effect in reducing LDL-C level and plaque ratio by gross oil red O staining， elevating the average fluorescence intensity of adiponectin， the p-AKT/AKT value， the protein level of PGC-1α， and the mRNA expression levels of UCP1 and PRDM16 （P＜0.05）. The high-dose JHTG group and the browning group showed similar efficacy in improving the pathology of the aorta. ConclusionJHTG may promote PVAT browning in AS model mice through the PI3K/AKT pathway， improve the endocrine function of PVAT， inhibit aortic inflammation， and thereby ameliorate the formation of AS plaques.

Objective: To evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

Objective To elucidate the mechanism by which the BANCR/miR-145-5p axis regulates the AKT-GLUT1/HK2 pathway through downstream targets Reg3A/DMBT1 to facilitate the Warburg effect in gastric cancer. Methods Expression levels of BANCR, miR-145-5p, Reg3A, and DMBT1 were detected by RT-qPCR and Western blot in gastric cancer tissues and cell lines. Dual-luciferase reporter assays confirmed targeted relationships. Glycolytic capacity was assessed via glucose uptake. Immunohistochemistry analyzed molecular expression in 60 paired clinical samples. The prognostic values of key molecules in the BANCR/miR-145-5p-Reg3A/DMBT1 axis were evaluated by Kaplan-Meier survival analysis and Cox proportional hazards regression model. Results BANCR was significantly upregulated, whereas miR-145-5p was downregulated in gastric cancer tissues, correlating with advanced TNM stage, lymph node metastasis, and poor differentiation. Reg3A and DMBT1 were identified as direct targets of miR-145-5p. Knockdown of BANCR or overexpression of miR-145-5p significantly suppressed Reg3A/DMBT1 expression, reduced AKT phosphorylation and GLUT1/HK2 levels, and inhibited glycolysis. Clinical analysis revealed positive correlations between Reg3A/DMBT1 expression and glycolytic markers, with both serving as independent risk factors for poor prognosis. Conclusion The BANCR/miR-145-5p axis activates the AKT pathway by targeting Reg3A/DMBT1, thereby promoting GLUT1/HK2/LDHA-mediated glycolysis and facilitating the Warburg effect in gastric cancer. This regulatory axis represents a potential therapeutic target and prognostic biomarker.

ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

AIM:To investigate the short-term efficacy of autologous serum eye drops combined with prednisolone acetate in the treatment of severe dry eye with grade II-III corneal injury.METHODS:Prospective, randomized, controlled single center study. Totally 122 patients(122 eyes, all enrolled patients had bilateral disease, with the more severely affected eye selected as the study eye; if the severity was similar between both eyes, the right eye was chosen as the study eye)with severe dry eye and grade II-III corneal injury who were treated at Wuhan University Affiliated Aier Eye Hospital from March 2023 to March 2025 were randomly divided into a control group(treated with sodium hyaluronate eye drops combined with autologous serum eye drops)and an observation group(treated with sodium hyaluronate eye drops, autologous serum eye drops combined with prednisolone acetate eye drops)using a random number table method. After continuous administration for 2 wk, the tear inflammatory reaction [interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)], subjective symptoms [ocular surface disease index(OSDI)score], lacrimal gland function [tear film break-up time(TBUT)and Schirmer tear secretion test(SⅠt)], corneal injury degree [corneal fluorescein staining(CFS)score] and corneal nerve function [total number and density of corneal subepithelial nerve(SBN)] before and after treatment were compared between the two groups, and the occurrence of adverse reactions during treatment was recorded. RESULTS:All patients have completed follow-up. The control group consisted of 61 cases and 61 eyes, with 24 males and 37 females, with an average age of 43.87±5.12y. There were 61 cases and 61 eyes in the observation group, including 21 males and 40 females, with an average age of 42.15±4.76y. At 1 and 2 wk after treatment, the levels of IL-6 and TNF-α in tears, OSDI score, and CFS score of the two groups were significantly lower than those before treatment, and those in the observation group were lower than those in the control group(all P<0.05). The total number of TBUT, SⅠt, SBN, and SBN density in both groups of patients increased significantly compared to before treatment, and the observation group was higher than the control group(all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups of patients during treatment(P=0.717).CONCLUSION:The combination of autologous serum eye drops and prednisolone acetate is effective in treating severe dry eye with grade II-III corneal injury. It can reduce patients' inflammatory reactions, subjective symptoms, and degree of corneal injury, promote the improvement of lacrimal gland function and corneal nerve function, providing a new strategy for corneal nerve repair. Furthermore, the combination therapy does not increase the risk of adverse reactions and shows good safety in short-term application.

ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.