Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To investigate the influencing factors for early hematoma enlargement(HE)in patients with spontaneous intracerebral hemorrhage(SICH).Methods A total of 311 pa-tients with SICH were selected as research subjects.Based on the occurrence of HE,they were divided into enlargement group and non-enlargement group.Clinical assessment indicators of patients with SICH were collected,and general information between the two groups was compared.The influencing factors for the occurrence of HE in patients with SICH were analyzed.Results Based on the presence of HE at a second CT examination within 6 to 12 hours,311 patients with SICH were divided into en-largement group(n=97)and non-enlargement group(n=214).Univariate analysis revealed signifi-cant differences between the two groups in terms of initial hematoma volume,regularity of hematoma margin,Glasgow Coma Scale(GCS)score,coagulation function,as well as the presence of swirl sign,lobulation sign,black hole sign,blend sign,lymphocyte count and neutrophil count(P＜0.05).Multivariate analysis indicated that GCS score,initial hematoma volume,history of antithrom-botic drug use,abnormal coagulation function and intracranial CT signs were independent influencing factors for HE(P＜0.05).Conclusion The occurrence of HE in patients with SICH is closely re-lated to GCS score,initial hematoma volume,history of antithrombotic drug use,abnormal coagulation function and intracranial CT signs.

Background::This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma (MM) during the induction phase of treatment with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods::We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1, 2013 to December 31, 2018.Results::There were 107 patients with International Staging System (ISS) III and 51 with paraprotein of light chain. Of these, 77 completed nine cycles of the BCD regimen. As the number of treatment cycles increased, the proportions of serum and urine immunofixation electrophoresis (IFE) tests elevated from 40.39% to 62.22% and 16.75% to 37.78%, respectively. More than 90% of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle, but that of urinary M protein was less than 60%. The detection rate of urinary M protein in light chain MM was more than 70% per cycle. Patients with a very good partial response (VGPR) had longer progression-free survival (PFS) than those with uncertain VGPR (32 vs. 26 months, p = 0.0336). Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation, those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly (27 vs. 22 months, p = 0.059). Conclusion::Urinary M protein detection rate is significantly lower than that in serum, leading to an overestimation of efficacy, premature reduction of treatment intensity, and shortened PFS. Precise response assessments are critical to treatment decisions and clinical diagnoses.

Irritable bowel syndrome(IBS)is accompanied by impaired intestinal mucosal barrier,and there is currently no ideal drug therapy.Acupuncture has obvious advantages in protecting intestinal mucosal barrier of IBS,but the molecular biological mechanism needs to be further studied.Based on the overall intestinal homeostasis in the"flora-intestinal epithelial dialogue"study to repair damaged intestinal mucosal barrier has become a hot research in this field.Therefore,based on the frontier basis,this paper discusses the feasibility mechanism of acupuncture in repairing IBS intestinal mucosal barrier injury from the perspective of intestinal flora-short-chain fatty acid-intestinal PPAR γ pathway-mediated intestinal epithelial cell metabolic reprogramming,in order to interpret the scientific connotation of acupuncture in repairing intestinal mucosal barrier injury,and provide a scientific basis for acupuncture therapy to play a greater role in public health care and for the modernization of traditional Chinese medicine.

Background::This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma (MM) during the induction phase of treatment with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods::We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1, 2013 to December 31, 2018.Results::There were 107 patients with International Staging System (ISS) III and 51 with paraprotein of light chain. Of these, 77 completed nine cycles of the BCD regimen. As the number of treatment cycles increased, the proportions of serum and urine immunofixation electrophoresis (IFE) tests elevated from 40.39% to 62.22% and 16.75% to 37.78%, respectively. More than 90% of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle, but that of urinary M protein was less than 60%. The detection rate of urinary M protein in light chain MM was more than 70% per cycle. Patients with a very good partial response (VGPR) had longer progression-free survival (PFS) than those with uncertain VGPR (32 vs. 26 months, p = 0.0336). Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation, those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly (27 vs. 22 months, p = 0.059). Conclusion::Urinary M protein detection rate is significantly lower than that in serum, leading to an overestimation of efficacy, premature reduction of treatment intensity, and shortened PFS. Precise response assessments are critical to treatment decisions and clinical diagnoses.

Cognitive impairment is a kind of senile disease that leads to the decline of personality and behavior ability of the elderly,which seriously affects the quality of daily life of patients.The prevalence rate of the disease increases year by year with the acceleration of the aging process of the society,and its incidence is affected by many risk factors.At this stage,the curative effect for middle and advanced patients is poor.So early identification and intervention to delay the progression of cognitive impairment have become the focus of relevant research.Blood pressure variability can lead to damage of target organs such as heart,brain tissue and kidney,which is closely related to cognitive impairment.In order to expand a new perspective of early intervention in cognitive impairment,this paper reviews the effects of blood pressure variability on different cognitive impairment and its possible pathogenic mechanism.

Irritable bowel syndrome(IBS)is accompanied by impaired intestinal mucosal barrier,and there is currently no ideal drug therapy.Acupuncture has obvious advantages in protecting intestinal mucosal barrier of IBS,but the molecular biological mechanism needs to be further studied.Based on the overall intestinal homeostasis in the"flora-intestinal epithelial dialogue"study to repair damaged intestinal mucosal barrier has become a hot research in this field.Therefore,based on the frontier basis,this paper discusses the feasibility mechanism of acupuncture in repairing IBS intestinal mucosal barrier injury from the perspective of intestinal flora-short-chain fatty acid-intestinal PPAR γ pathway-mediated intestinal epithelial cell metabolic reprogramming,in order to interpret the scientific connotation of acupuncture in repairing intestinal mucosal barrier injury,and provide a scientific basis for acupuncture therapy to play a greater role in public health care and for the modernization of traditional Chinese medicine.

Objective To observe the effect of moxibustion of"Zusanli"and"Ganshu"on the intestinal flora of colorectal cancer cells liver metastasis in nude mice and its possible mechanism was explored.Methods HCT116-GFP colon cancer cells were inoculated by spleen injection,sixty SPF BALB/c male nude mice were divided into model control group,Pre-Mox group,Post-Mox group,Pre-Post-Mox group.Bilateral"Ganshu(BL18)"and"Zusanli(ST36)"acupoints were selected for moxibustion intervention for once a day for 10 minutes each time.the tumor formation rate,liver metastasis rate and the number of tumor of each group were calculated.Furthermore,16S rRNA analysis was used to assess their microbial diversity.Results Moxibustion intervention can significantly reduce the rate of liver metastasis,reduce the number of metastatic foci.Compared with the model control group,Lactobacillus_reuteri and Robinsoniella_peoriensis were significantly lower in Pre-Mox group(P<0.05).Lactobacillus_gasseri decreased significantly,Clostridium_cocleatum and Erysipelatoclostrdum_ramosum multiplex increased significantly in the Post-Mox group(P<0.01).Pre-Post-Mox mice had significantly decreased levels of Lactobacillus_gasseri,and Clostridium_cocleatum,Akkermansia_muciniphila and Clostridium_cocleatum were significantly increased(P<0.05).LEfSe Difference analysis showed that the Pre-Mox group was mainly changed by Coprobacillus;the Post-Mox group was marked by Muribaculaceae and erysipelas;the Pre-Post-Mox group took Verrucomicrobia,Akkermansia_muciniphila and erysipelas as signs.Conclusion Moxibustion could exert an inhibitory effect on CRC liver metastasis,especially the 5-week Pre-PostMox treatment showed the best inhibitory.The potential mechanism might rely on the alteration of microbiota diversity and composition.

Objective To observe the effect of moxibustion of"Zusanli"and"Ganshu"on the intestinal flora of colorectal cancer cells liver metastasis in nude mice and its possible mechanism was explored.Methods HCT116-GFP colon cancer cells were inoculated by spleen injection,sixty SPF BALB/c male nude mice were divided into model control group,Pre-Mox group,Post-Mox group,Pre-Post-Mox group.Bilateral"Ganshu(BL18)"and"Zusanli(ST36)"acupoints were selected for moxibustion intervention for once a day for 10 minutes each time.the tumor formation rate,liver metastasis rate and the number of tumor of each group were calculated.Furthermore,16S rRNA analysis was used to assess their microbial diversity.Results Moxibustion intervention can significantly reduce the rate of liver metastasis,reduce the number of metastatic foci.Compared with the model control group,Lactobacillus_reuteri and Robinsoniella_peoriensis were significantly lower in Pre-Mox group(P<0.05).Lactobacillus_gasseri decreased significantly,Clostridium_cocleatum and Erysipelatoclostrdum_ramosum multiplex increased significantly in the Post-Mox group(P<0.01).Pre-Post-Mox mice had significantly decreased levels of Lactobacillus_gasseri,and Clostridium_cocleatum,Akkermansia_muciniphila and Clostridium_cocleatum were significantly increased(P<0.05).LEfSe Difference analysis showed that the Pre-Mox group was mainly changed by Coprobacillus;the Post-Mox group was marked by Muribaculaceae and erysipelas;the Pre-Post-Mox group took Verrucomicrobia,Akkermansia_muciniphila and erysipelas as signs.Conclusion Moxibustion could exert an inhibitory effect on CRC liver metastasis,especially the 5-week Pre-PostMox treatment showed the best inhibitory.The potential mechanism might rely on the alteration of microbiota diversity and composition.

Objective:To investigate the difference of urinary protein components in pregnant women with pre-eclampsia (PE) with different degrees of proteinuria and the correlation between 24-hour urinary protein quantification and estimated glomerular filtration rate (eGFR).Methods:Clinical data of 101 PE pregnant women who were delivered in Renji Hospital, Shanghai Jiao Tong University School of Medicine from July 2018 to June 2022 were retrospectively analyzed. According to 24-hour urinary protein quantification, they were divided into 3 groups, including 40 cases of mild proteinuria group (24-hour urinary protein quantification ≤2.0 g), 21 cases of moderate proteinuria group (2.0 g<24-hour urinary protein quantification ≤5.0 g), 40 cases of severe proteinuria group (24-hour urinary protein quantification >5.0 g). The general clinical data, urinary protein index and renal function index of PE pregnant women in 3 groups were compared. The eGFR was calculated based on age, serum creatinine (sCr), blood urea nitrogen (BUN) and serum albumin (sAlb). Correlation analysis was conducted between 24-hour urinary protein quantification and each index of eGFR.Results:(1) General clinical data: the median PE onset week (31 weeks) and delivery gestational week [(36.4±3.6) weeks] of PE pregnant women in the mild proteinuria group were later than those in the moderate proteinuria group [median PE onset: 22 weeks, delivery: (32.2±4.2) weeks] and severe proteinuria group [median PE onset: 25 weeks, delivery: (29.6±3.4) weeks]; systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminotransferase levels and the incidence of fetal growth restriction were lower than those in the moderate and severe proteinuria groups; median newborn birth weight (3 150 g) was higher than those in the moderate proteinuria group (1 305 g) and the severe proteinuria group (1 042 g), respectively. The differences were statistically significant (all P<0.05). (2) Urinary protein index: the 24-hour urinary protein quantification, urinary microalbumin (mAlb) and urinary transferrin (TRF) levels of PE pregnant women in the mild proteinuria group, moderate proteinuria group and severe proteinuria group were increased successively, and the differences were statistically significant (all P<0.05). The median urinary α1-microglobulin (α1-MG) level of PE pregnant women in the severe proteinuria group (50 mg/L) was significantly higher than those in the mild proteinuria group (17 mg/L) and moderate proteinuria group (22 mg/L; all P<0.05), but there was no significant difference between the mild proteinuria group and the moderate proteinuria group ( P>0.05). There was no significant difference in the median urinary β2-microglobulin (β2-MG) level among the 3 groups ( P=0.632). (3) Renal function index: sAlb and eGFR of PE pregnant women in the mild proteinuria group, moderate proteinuria group and severe proteinuria group were successively decreased, and BUN was successively increased, respectively, and the differences were statistically significant (all P<0.05). The sCr level of PE pregnant women in the severe proteinuria group was significantly higher than those in the mild proteinuria group and the moderate proteinuria group (all P<0.05), but there was no significant difference between the mild proteinuria group and the moderate proteinuria group ( P>0.05). (4) Correlation analysis: the 24-hour urinary protein quantification of PE pregnant women was significantly negatively correlated with eGFR ( r=-0.645, P<0.001), and was correlated with the variables sAlb ( r=-0.549, P<0.001), sCr ( r=0.582, P<0.001) and BUN ( r=-0.657, P<0.001) in the eGFR calculation formula. The 24-hour urinary protein quantification were significantly negatively correlated with the gestational weeks of PE onset, gestational weeks of termination of pregnancy and newborn birth weight (all P<0.05). Conclusions:The protein composition in the urine of PE pregnant women with different degrees of proteinuria is not different, but the protein level is significantly different. There is a significant negative correlation between the increase of 24-hour urinary protein quantification and the decrease of eGFR.