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 clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To investigate the current status of quality management in clinical pharmacist training bases in China， and to provide references for the standardized development and improvement of these bases. METHODS A combined approach of questionnaire survey and on-site investigation was adopted， targeting the healthcare highly sought-after talent （clinical pharmacist） training bases in 31 provinces of China as well as the clinical pharmacist training bases affiliated with the Chinese Hospital Association. A training quality management evaluation index system consisting of 25 tertiary indicators was established. Investigations were conducted from two dimensions： structural quality of training and quality management of training processes. Data were statistically analyzed using descriptive statistical methods. RESULTS On-site investigations were completed for 297 clinical pharmacist training bases across the 31 provinces， among which 284 were affiliated with the Chinese Hospital Association and 271 were healthcare highly sought-after talent （clinical pharmacist） training bases. In terms of structural quality， the core indicator compliance rate for hospital-level training systems exceeded 80%， the rate of special fund utilization for designated purposes reached 80.13%， and the overall compliance rate for software and hardware facilities surpassed 88%. A total of 1 348 preceptors were employed across the training bases， among whom those with senior professional titles and full-time specialist clinical pharmacists as lead preceptors accounted for 62.91% and 94.36%， respectively. Regarding process quality， the compliance rate for “establishment of clinical practice teaching groups in accordance with regulations during clinical department rotations” was 85.19%， and 79.80% and 76.09% of the bases were found to implement strict confidentiality in theoretical examinations and meet the required scale of assessment cases， respectively. However， formal documents of corresponding training management regulations were formulated in only 57.91% of the bases， and the completeness and standardization rate of training manual completion was merely 47.47%. In addition， considerable disparities in quality management levels were observed among provinces， with issues in training process quality being particularly prominent. CONCLUSIONS The management system， hardware facilities， and preceptor staffing of clinical pharmacist training bases in China are relatively well-established， yet notable variations in quality management exist among training bases across different provinces.

AIM To study the chemical constituents from the branches and leaves of Michelia yunnanensis Franch.ex Finet & Gagnep.and their anti-inflammatory activities.METHODS The methanol extract was isolated and purified by silica gel,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as dihydrodehydrodiconifenyl alcohol(1),8-hydroxypinoresinol(2),lariciresinol(3),isolariciresinol(4),(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(5),thero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxy-propanol(6),evofolin B(7),(E)-p-coumaryl alcohol γ-O-methyl ether(8),ω-hydroxypropioguaiacone(9),sinapaldehyde(10),isoscopoletin(11),6-hydroxy-5,7-dimethoxycoumarin(12),2α,3α-dihydroxy-2-methylbutyrolactone(13),6-hydroxy-3(1-hydroxy-1-methylethyl)-6-methyl-2-cyclohexen-1-one(14),benzofuran-2-carboxaldehyde(15),3,4-dihydroxy-5-methoxybenzaldehyde(16),3,5-dimethoxy-4-hydroxybenzaldehyde(17),3,4-dihydroxybenzaldehyde(18),3,4-dihydroxybenzoic methyl ester(19),vanillic acid(20).The inhibition rate of compound 1 on NO was 45.39％±0.32％.CONCLUSION Compounds 1-16,18-20 are first isolated from this plant.Compound 1 has anti-inflammatory activity.

Objective:To analyze the correlation between blood glucose index and peripheral neuropathy in type 2 diabetes patients under continuous blood glucose monitoring.Methods:A total of 110 patients with type 2 diabetes admitted to the Lu′an Hospital Affiliated to Anhui Medical University from November 2022 to January 2024 were retrospectively observed, and the blood glucose indexes of patients were monitored by continuous glucose meter [glucose time in range (TIR), mean blood glucose (MBG), estimated hemoglobin A 1c (eHbA 1c), blood glucose standard deviation (SD), coefficient of variation (CV), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), means of daily differences (MODD), etc ]. All patients with type 2 diabetes were grouped according to whether they had peripheral neuropathy or not, and were divided into the developing group and the non-developing group. General data and blood glucose indexes of the two groups were collected and sorted out. Receiver operating characteristic (ROC) curve was used to analyze the value of various blood glucose indicators in predicting peripheral neuropathy in patients with type 2 diabetes. Spearman correlation analysis was also used to evaluate the correlation between blood glucose index and peripheral neuropathy. Results:The disease course, TIR, MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD of the occurrence group were significantly different from those of the non-occurrence group (all P<0.05). By plotting the ROC curve, It was found that the area under the curve (AUC) of TIR, MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD predicting peripheral neuropathy in patients with type 2 diabetes were 0.942, 0.840, 0.705, 0.759, 0.819, 0.813, 0.857 and 0.677, respectively. The AUC of the combined prediction was 0.971(95% CI: 0.946-0.997), which was higher than that of the single indicator (all P<0.05). Spearman correlation assessment showed a negative correlation between TIR and peripheral neuropathy ( r=-0.738, P<0.05). MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD were positively correlated with peripheral neuropathy ( r=0.554, 0.376, 0.452, 0.490, 0.527, 0.625, 0.272, all P<0.05). Conclusions:Based on continuous blood glucose monitoring, the blood glucose index of type 2 diabetes patients is closely related to peripheral neuropathy, and the above blood glucose index can accurately predict peripheral neuropathy, providing a reference for reducing or preventing the occurrence of peripheral neuropathy.

Objectives:Coronary slow flow(CSF)has long been regarded as a marker of coronary microvascular dysfunction(CMD).This study aims to evaluate the diagnostic value of CSF for CMD in patients with angina and nonobstructive coronary arteries(ANOCA).Methods:The study data were derived from the ANOCA-CMD prospective cohort study.All enrolled patients underwent coronary angiography and concurrent coronary physiological assessments in the left anterior descending artery using pressure-wire and thermodilution techniques to obtain coronary flow reserve(CFR)and the index of microcirculatory resistance(IMR).Based on the results,CMD was classified into four subtypes:CMD with elevated IMR(IMR≥25),CMD with reduced CFR(CFR<2.5),CMD with either reduced CFR or elevated IMR(CFR<2.5 or IMR≥25),and CMD with both reduced CFR and elevated IMR(CFR<2.5 and IMR≥25).The corrected thrombolysis in myocardial infarction(TIMI)frame count(CTFC)in the left anterior descending artery was calculated from coronary angiography images,with CSF defined as CTFC>27.This study evaluated the correlation between CTFC,CFR,and IMR,and investigated the diagnostic value of CSF for CMD in ANOCA patients.Results:A total of 103 ANOCA patients were enrolled in this study,with a mean age of(64.2±10.6)years,and 53.4％were female.Among them,57 patients(55.3％)were diagnosed with coronary slow flow.Patients with slow flow had higher IMR(P<0.001)and CFR(P=0.041).Similarly,the proportion of CMD with elevated IMR was higher in the slow flow group(P<0.001),while the proportion of CMD with reduced CFR was lower(P=0.044).There was no significant difference between the groups in the proportions of CMD with either reduced CFR or elevated IMR or CMD with both reduced CFR and elevated IMR(all P>0.05).CTFC was positively correlated with hyperemic mean transit time(r=0.424,P<0.001),IMR(r=0.430,P<0.001),and CFR(r=0.211,P=0.032).The area under the curve(AUC)of CTFC for diagnosing CMD with elevated IMR was 0.721(95％CI:0.623-0.819)with an accuracy of 67％(57％,76％),for diagnosing CMD with reduced CFR was 0.610(95％CI:0.499-0.720)with an accuracy of 60％(50％,70％),for diagnosing CMD with either reduced CFR or elevated IMR was 0.549(95％CI:0.425-0.673)with an accuracy of 47％(37％,57％),and for diagnosing CMD with both reduced CFR and elevated IMR was 0.582(95％CI:0.471-0.693)with an accuracy of 47％(37％,57％).Thus,CSF demonstrated limited diagnostic values across all subtypes of CMD.Conclusions:In ANOCA patients,CSF cannot serve as an effective diagnostic marker for CMD.Therefore,in clinical practice,the slow flow phenomenon should not be directly equated with the presence of coronary microvascular dysfunction in ANOCA patients.

AIM To study the chemical constituents from the branches and leaves of Michelia yunnanensis Franch.ex Finet & Gagnep.and their anti-inflammatory activities.METHODS The methanol extract was isolated and purified by silica gel,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as dihydrodehydrodiconifenyl alcohol(1),8-hydroxypinoresinol(2),lariciresinol(3),isolariciresinol(4),(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(5),thero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxy-propanol(6),evofolin B(7),(E)-p-coumaryl alcohol γ-O-methyl ether(8),ω-hydroxypropioguaiacone(9),sinapaldehyde(10),isoscopoletin(11),6-hydroxy-5,7-dimethoxycoumarin(12),2α,3α-dihydroxy-2-methylbutyrolactone(13),6-hydroxy-3(1-hydroxy-1-methylethyl)-6-methyl-2-cyclohexen-1-one(14),benzofuran-2-carboxaldehyde(15),3,4-dihydroxy-5-methoxybenzaldehyde(16),3,5-dimethoxy-4-hydroxybenzaldehyde(17),3,4-dihydroxybenzaldehyde(18),3,4-dihydroxybenzoic methyl ester(19),vanillic acid(20).The inhibition rate of compound 1 on NO was 45.39％±0.32％.CONCLUSION Compounds 1-16,18-20 are first isolated from this plant.Compound 1 has anti-inflammatory activity.

Objective:To analyze the correlation between blood glucose index and peripheral neuropathy in type 2 diabetes patients under continuous blood glucose monitoring.Methods:A total of 110 patients with type 2 diabetes admitted to the Lu′an Hospital Affiliated to Anhui Medical University from November 2022 to January 2024 were retrospectively observed, and the blood glucose indexes of patients were monitored by continuous glucose meter [glucose time in range (TIR), mean blood glucose (MBG), estimated hemoglobin A 1c (eHbA 1c), blood glucose standard deviation (SD), coefficient of variation (CV), largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), means of daily differences (MODD), etc ]. All patients with type 2 diabetes were grouped according to whether they had peripheral neuropathy or not, and were divided into the developing group and the non-developing group. General data and blood glucose indexes of the two groups were collected and sorted out. Receiver operating characteristic (ROC) curve was used to analyze the value of various blood glucose indicators in predicting peripheral neuropathy in patients with type 2 diabetes. Spearman correlation analysis was also used to evaluate the correlation between blood glucose index and peripheral neuropathy. Results:The disease course, TIR, MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD of the occurrence group were significantly different from those of the non-occurrence group (all P<0.05). By plotting the ROC curve, It was found that the area under the curve (AUC) of TIR, MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD predicting peripheral neuropathy in patients with type 2 diabetes were 0.942, 0.840, 0.705, 0.759, 0.819, 0.813, 0.857 and 0.677, respectively. The AUC of the combined prediction was 0.971(95% CI: 0.946-0.997), which was higher than that of the single indicator (all P<0.05). Spearman correlation assessment showed a negative correlation between TIR and peripheral neuropathy ( r=-0.738, P<0.05). MBG, eHbA 1c, SD, CV, LAGE, MAGE and MODD were positively correlated with peripheral neuropathy ( r=0.554, 0.376, 0.452, 0.490, 0.527, 0.625, 0.272, all P<0.05). Conclusions:Based on continuous blood glucose monitoring, the blood glucose index of type 2 diabetes patients is closely related to peripheral neuropathy, and the above blood glucose index can accurately predict peripheral neuropathy, providing a reference for reducing or preventing the occurrence of peripheral neuropathy.

Objective To explore the influence of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with brain-computer interface rehabilitation robot in patients with upper limb motor dysfunction after stroke.Methods A total of 126 patients with upper limb motor dysfunction after stroke were divided into the combined group(61 cases,low-frequency rTMS combined with brain-computer interface rehabilitation robot on the basis of routine rehabilitation treatment)and the magnetic stimulation group(65 cases,low-frequency rTMS on the basis of routine rehabilitation treatment)according to different treatment methods,and both groups were continuously treated for 3 weeks.The upper limb motor function[upper-extremity Fugl-Meyer scale(UFMA),action research arm test(ARAT)],hand Brunnstrom staging,upper limb surface electromyography indicators[root mean square(RMS)and integrated electromyography(iEMG)of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle],cerebral artery hemodynamics[systolic blood flow velocity(Vs),resistance index(RI),mean blood flow velocity(Vm)]and ratio of fractional anisotropy(FA)of central region of brain lesion and FA of mirror-image region of healthy cerebral hemisphere(rFA)were observed before and after treatment in the two groups.Results Compared with the magnetic stimulation group,the UFMA score,ARAT score,hand Brunnstrom staging,Vs,Vm and rFA were higher after treatment in the combined group(P＜0.05).The RMS and iEMG of biceps brachii,triceps brachii,deltoid anterior bundle and deltoid middle bundle were higher in the combined group compared with those of the magnetic stimulation group(P＜0.05),while the RI was lower(P＜0.05).Conclusion Combined treatment can more effectively improve the upper limb motor function of patients,enhance hand activity ability,promote the recovery of upper limb muscle and nerve function,and regulate the hemodynamics of cerebral arteries.