Objective To investigate the association of baseline cerebral blood flow （CBF） and cerebral metabolic rate of oxygen （CMRO2） with sleep structure disorder after thrombolytic therapy in stroke patients， as well as their value in clinical assessment. Methods A total of 145 patients with stroke were enrolled as subjects， and all of them received thrombolytic therapy in our hospital from January 2023 to June 2025. Before thrombolytic therapy， 3.0 T magnetic resonance imaging was used to obtain relative CBF （rCBF） and relative CMRO2 （rCMRO2）， and rCBF/rCMRO2 ratio was calculated. At week 1 after thrombolysis， overnight polysomnography （PSG） was conducted to obtain parameters such as total sleep time， sleep efficiency， the proportion of each NREM stage， and REM sleep duration. According to the presence or absence of sleep structure disorder， the subjects were divided into disorder group and non-disorder group. The Pearson correlation method was used for correlation analysis. A multivariate logistic regression analysis was used to identify the influencing factors for sleep structure disorder in subjects after thrombolytic therapy. The receiver operating characteristic （ROC） curve was plotted to analyze the performance of rCBF/rCMRO2 ratio in predicting sleep structure disorder in subjects after thrombolytic therapy. Results Compared with the non-disorder group， the disorder group had significantly higher age， infarct volume， NIHSS score on admission， and proportion of patients with infarction in the thalamus （P<0.05）. Compared with the non-disorder group， the disorder group had significantly lower rCBF， rCMRO2， rCBF/rCMRO2 ratio， total sleep time， proportion of NREM 3 sleep， proportion of REM sleep， and sleep efficiency （P<0.05） and significantly higher proportion of NREM 1 sleep and sleep arousal index （P<0.05）. The Pearson correlation analysis showed that rCBF， rCMRO2， and rCBF/rCMRO2 ratio were positively correlated with total sleep time， proportion of NREM 3 sleep， proportion of REM sleep， and sleep efficiency （P<0.001） and were negatively correlated with the proportion of NREM 1 sleep and sleep arousal index （P<0.001）. The Logistic regression analysis showed that age， infarct volume， infarction location （thalamus）， and NIHSS score on admission were risk factors for sleep structure disorder in stroke patients after thrombolytic therapy （P<0.05）， while rCBF， rCMRO2， and rCBF/rCMRO2 ratio were protective factors against sleep structure disorder （P<0.05）. The ROC curve analysis showed that rCBF/rCMRO2 ratio had an area under the ROC curve of 0.901 （95% CI 0.869-0.938） in predicting sleep structure disorder in stroke patients after thrombolytic therapy， with a sensitivity of 95.50% and a specificity of 82.40%. Conclusion Baseline rCBF， rCMRO2， and rCBF/rCMRO2 ratio are closely associated with sleep structure disorder in stroke patients after thrombolytic therapy， among which rCBF/rCMRO2 ratio has excellent performance in predicting sleep structure disorder and can be used as a sensitive indicator for clinical assessment of high-risk patients.
Stroke

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

Objective:To evaluate the clinical outcomes of radical resection and perioperative management strategies in hepatocellular carcinoma (HCC) patients with major vascular invasion and tumor thrombus.Methods:This is a retrospective case series study. From January 2010 to December 2022,clinicopathological data of 387 HCC patients who underwent liver resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. In the cohort,there were 326 males (84.2%) and 61 females (15.8%),with an age ( M(IQR)) of 54(16) years (range: 16 to 82 years). One hundred and nineteen patients (30.7%) had macrovascular invasion without thrombus and 268 patients(69.3%) had macrovascular thrombus. Categorical variables were presented as frequencies (percentages). Survival rates were calculated using life-table analysis,and Kaplan-Meier curves were employed to depict overall survival(OS) and recurrence-free survival (RFS). Independent prognostic factors were identified by univariate and multivariate Cox regression. Results:Among 387 patients,R0 resection was achieved in 359 cases (92.8%),with R1 or R2 resection in 28 cases (7.2%). Excluding in-hospital deaths,the 354 R0-resected patients had a median OS of 19.8 months, with 1-, 3-, and 5-year OS rates were 63.3%, 35.1%, and 22.4%, respectively; median RFS was 5.6 months,and 1-, 3-, and 5-year RFS was 34.0%,18.0%,and 14.4%, respectively. Patients receiving preoperative therapy showed a median OS of 26.0 months,1-, 3-, and 5-year OS rates were 75.5%, 48.4%, and 32.5%, respectively. There was no significant difference in the OS of patients with or without preoperative therapy ( P>0.05). The median OS time of patients who received postoperative adjuvant therapy was 53.0 months, and the 1-, 3-, and 5-year OS rates were 87.9%, 59.2%, and 34.8%, respectively. The median OS time of patients who did not receive postoperative adjuvant therapy was 13.7 months, and 1-, 3-, and 5-year OS rates were 56.7%, 31.7%, and 22.4%, respectively ( P<0.01). The median RFS of patients who received postoperative adjuvant therapy was 11.6 months, and the 1-, 3-, and 5-year RFS rates were 49.6%, 29.8%, and 26.8%, respectively. The median RFS of patients who did not receive postoperative adjuvant therapy was 4.2 months, and the 1-,3-,and 5-year RFS rates were 29.2%, 16.1%, and 12.5%, respectively ( P<0.01). Multivariate analysis identified that maximum tumor diameter,postoperative adjuvant therapy,and treatment after recurrence were the independent predictors of the OS of patients with major vascular invasion and tumor thrombus (all P<0.05),while age,surgical approach,and postoperative adjuvant therapy independently influenced the RFS of patients with major vascular invasion and tumor thrombus(all P<0.05). Conclusions:HCC patients with vascular invasion/thrombus could benefit from surgery-based multimodal therapy after careful evaluation. Postoperative adjuvant therapy significantly reduces recurrence and prolongs patients′ survival.

Biliary tract cancers comprise a spectrum of invasive tumors with poor progno-sis, which are composed of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. Due to the difficulty of early diagnosis of biliary tract cancers, most patients are diagnosed in the late stage with low surgical resection rates. Moreover, the efficacy of traditional chemotherapy regimens, such as gemcitabine plus cisplatin, is limited. In recent years, the rise of immune checkpoint inhibitors and molecular targeted therapy have provided new treatment options for patients with advanced biliary tract cancers. Based on literature reports and team experiences, the authors discuss the latest research progress in the immunotherapy and molecular targeted therapy of biliary tract cancers, and explore future treatment strategies.

Acute kidney injury (AKI) usually requires renal replacement therapy (RRT). Common RRT modes include peritoneal dialysis, continuous renal replacement therapy, intermittent hemodialysis and continuous low-efficiency hemodialysis. In clinical practice, there is still controversy over how to select the appropriate RRT mode for AKI patients and when initiating RRT is more beneficial for AKI patients. This article summarizes previous studies on the impact of RRT mode and initiation timing on the prognosis of AKI patients, with the aim of providing assistance for clinical decision-making.

Acute kidney injury (AKI) usually requires renal replacement therapy (RRT). Common RRT modes include peritoneal dialysis, continuous renal replacement therapy, intermittent hemodialysis and continuous low-efficiency hemodialysis. In clinical practice, there is still controversy over how to select the appropriate RRT mode for AKI patients and when initiating RRT is more beneficial for AKI patients. This article summarizes previous studies on the impact of RRT mode and initiation timing on the prognosis of AKI patients, with the aim of providing assistance for clinical decision-making.

Biliary tract cancers comprise a spectrum of invasive tumors with poor progno-sis, which are composed of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. Due to the difficulty of early diagnosis of biliary tract cancers, most patients are diagnosed in the late stage with low surgical resection rates. Moreover, the efficacy of traditional chemotherapy regimens, such as gemcitabine plus cisplatin, is limited. In recent years, the rise of immune checkpoint inhibitors and molecular targeted therapy have provided new treatment options for patients with advanced biliary tract cancers. Based on literature reports and team experiences, the authors discuss the latest research progress in the immunotherapy and molecular targeted therapy of biliary tract cancers, and explore future treatment strategies.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Objective:To evaluate the clinical outcomes of radical resection and perioperative management strategies in hepatocellular carcinoma (HCC) patients with major vascular invasion and tumor thrombus.Methods:This is a retrospective case series study. From January 2010 to December 2022,clinicopathological data of 387 HCC patients who underwent liver resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. In the cohort,there were 326 males (84.2%) and 61 females (15.8%),with an age ( M(IQR)) of 54(16) years (range: 16 to 82 years). One hundred and nineteen patients (30.7%) had macrovascular invasion without thrombus and 268 patients(69.3%) had macrovascular thrombus. Categorical variables were presented as frequencies (percentages). Survival rates were calculated using life-table analysis,and Kaplan-Meier curves were employed to depict overall survival(OS) and recurrence-free survival (RFS). Independent prognostic factors were identified by univariate and multivariate Cox regression. Results:Among 387 patients,R0 resection was achieved in 359 cases (92.8%),with R1 or R2 resection in 28 cases (7.2%). Excluding in-hospital deaths,the 354 R0-resected patients had a median OS of 19.8 months, with 1-, 3-, and 5-year OS rates were 63.3%, 35.1%, and 22.4%, respectively; median RFS was 5.6 months,and 1-, 3-, and 5-year RFS was 34.0%,18.0%,and 14.4%, respectively. Patients receiving preoperative therapy showed a median OS of 26.0 months,1-, 3-, and 5-year OS rates were 75.5%, 48.4%, and 32.5%, respectively. There was no significant difference in the OS of patients with or without preoperative therapy ( P>0.05). The median OS time of patients who received postoperative adjuvant therapy was 53.0 months, and the 1-, 3-, and 5-year OS rates were 87.9%, 59.2%, and 34.8%, respectively. The median OS time of patients who did not receive postoperative adjuvant therapy was 13.7 months, and 1-, 3-, and 5-year OS rates were 56.7%, 31.7%, and 22.4%, respectively ( P<0.01). The median RFS of patients who received postoperative adjuvant therapy was 11.6 months, and the 1-, 3-, and 5-year RFS rates were 49.6%, 29.8%, and 26.8%, respectively. The median RFS of patients who did not receive postoperative adjuvant therapy was 4.2 months, and the 1-,3-,and 5-year RFS rates were 29.2%, 16.1%, and 12.5%, respectively ( P<0.01). Multivariate analysis identified that maximum tumor diameter,postoperative adjuvant therapy,and treatment after recurrence were the independent predictors of the OS of patients with major vascular invasion and tumor thrombus (all P<0.05),while age,surgical approach,and postoperative adjuvant therapy independently influenced the RFS of patients with major vascular invasion and tumor thrombus(all P<0.05). Conclusions:HCC patients with vascular invasion/thrombus could benefit from surgery-based multimodal therapy after careful evaluation. Postoperative adjuvant therapy significantly reduces recurrence and prolongs patients′ survival.