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.

Objective:To explore and summarize the key points and main treatment measures for successfully treating sever Rickettsia japonica infection. Methods:A 69-year-old female with severe Japanese spotted fever was admitted to Yichang Central People’s Hospital on May 15 in 2024 and was successfully treated. The clinical data of the patient were retrospectively analyzed.Results:The patient was quickly progressed to severe pneumonia，septic shock，dry gangrene of the extremities during the treatment process，and hepatic dysfunction，cardiac dysfunction，renal dysfunction and gastrointestinal hemorrhage were observed. After active anti-infection，anti-shock，continuous renal replacement therapy，and symptomatic supportive treatment，the patient’s condition improved，but the dry gangrene of the limbs was irreversible，ultimately leading to amputation.Conclusion:Timely diagnosis，early and active anti infective treatment，and effective management of various complications are the key to successfully treating cases of Ricketttsia Japonica

Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid decline in renal function within a short period.Its pathogenesis involves multiple processes,including oxidative stress,inflammatory responses,and programmed cell death,while effective pharmacological interventions remain lacking.Current studies have indicated that asiaticoside,a natural active compound,exhibits nephroprotective potential in the intervention of AKI.The potential mechanisms include the activation of antioxidant signaling such as nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 to mitigate oxidative injury,the regulation of key inflammatory pathways including nuclear factor-κB/NOD-like receptor thermal protein domain associated protein 3,and Janus kinase 2/signal transducer and activator of transcription 3 to suppress inflammation and modulate macrophage polarization;it promotes mitophagy by influencing the expression of apoptosis-related proteins and activating the recombinant sirtuin 1-forkhead box-O3-phosphatase and tensin homolog-induced kinase 1-Parkin pathway so as to maintain cellular homeostasis.As a multi-target natural compound,asiaticoside holds promise for providing novel intervention strategies in the clinical treatment of AKI,yet its efficacy and safety still require validation through large-sample clinical trials.

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.

Objective:To explore and summarize the key points and main treatment measures for successfully treating sever Rickettsia japonica infection. Methods:A 69-year-old female with severe Japanese spotted fever was admitted to Yichang Central People’s Hospital on May 15 in 2024 and was successfully treated. The clinical data of the patient were retrospectively analyzed.Results:The patient was quickly progressed to severe pneumonia，septic shock，dry gangrene of the extremities during the treatment process，and hepatic dysfunction，cardiac dysfunction，renal dysfunction and gastrointestinal hemorrhage were observed. After active anti-infection，anti-shock，continuous renal replacement therapy，and symptomatic supportive treatment，the patient’s condition improved，but the dry gangrene of the limbs was irreversible，ultimately leading to amputation.Conclusion:Timely diagnosis，early and active anti infective treatment，and effective management of various complications are the key to successfully treating cases of Ricketttsia Japonica

Objective To construct c-Met CAR-T cells secreting PD-1 antibodies to reduce immune inhibitory effect of tumor cells and enhance the efficacy of CAR-T cell therapy against pancreatic cancer.Methods Kaplan-Meier Plotter,GEPIA,and Timer 2.0 bioinformatics databases were used to analyze c-Met expression in pancreatic cancer and its correlation with survival and immune infiltration status.In clinical samples of pancreatic cancer and pancreatic cancer Aspc-1 cells,c-Met and PD-L1 expressions were detected using immunohistochemistry or flow cytometry.Using gene editing technology,PD-1 secretory antibodies and HIS tags were linked to second-generation c-Met CAR molecules to construct PD-1/c-Met CAR plasmids,which were then packaged into lentiviruses for infection of activated T cells.The positive rate and cell subset distribution of CAR-T cells were analyzed with flow cytometry,and secretory PD-1 antibodies in cell supernatants were detected using Western blotting.The target cell killing efficiency and proliferative activity of the modified CAR-T cells were evaluated after activation,and cytokine secretion was analyzed using ELISA.Results The expression of c-Met was significantly higher in pancreatic cancer than in normal tissues,and its expression level was negatively correlated with the patients'survival and positively correlated with immune cell infiltration.The clinical samples of pancreatic cancer tissues expressed significantly higher levels of c-Met and PD-L1 than the adjacent tissues,and 90.7%and 57.7%of Aspc-1 cells were positive for c-Met and PD-L1,respectively.The constructed PD-1/c-Met CAR-T cells were capable of secreting PD-1 antibodies and showed a significantly higher killing efficiency against tumor cells than c-Met CAR-T cells at an effector-to-target ratio of 20:1,with also a higher proliferative activity after target cell stimulation and higher levels of IL-2 and TNF-α secretin.Conclusion PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.

Objective To construct c-Met CAR-T cells secreting PD-1 antibodies to reduce immune inhibitory effect of tumor cells and enhance the efficacy of CAR-T cell therapy against pancreatic cancer.Methods Kaplan-Meier Plotter,GEPIA,and Timer 2.0 bioinformatics databases were used to analyze c-Met expression in pancreatic cancer and its correlation with survival and immune infiltration status.In clinical samples of pancreatic cancer and pancreatic cancer Aspc-1 cells,c-Met and PD-L1 expressions were detected using immunohistochemistry or flow cytometry.Using gene editing technology,PD-1 secretory antibodies and HIS tags were linked to second-generation c-Met CAR molecules to construct PD-1/c-Met CAR plasmids,which were then packaged into lentiviruses for infection of activated T cells.The positive rate and cell subset distribution of CAR-T cells were analyzed with flow cytometry,and secretory PD-1 antibodies in cell supernatants were detected using Western blotting.The target cell killing efficiency and proliferative activity of the modified CAR-T cells were evaluated after activation,and cytokine secretion was analyzed using ELISA.Results The expression of c-Met was significantly higher in pancreatic cancer than in normal tissues,and its expression level was negatively correlated with the patients'survival and positively correlated with immune cell infiltration.The clinical samples of pancreatic cancer tissues expressed significantly higher levels of c-Met and PD-L1 than the adjacent tissues,and 90.7%and 57.7%of Aspc-1 cells were positive for c-Met and PD-L1,respectively.The constructed PD-1/c-Met CAR-T cells were capable of secreting PD-1 antibodies and showed a significantly higher killing efficiency against tumor cells than c-Met CAR-T cells at an effector-to-target ratio of 20:1,with also a higher proliferative activity after target cell stimulation and higher levels of IL-2 and TNF-α secretin.Conclusion PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.

Objective:To evaluate the risk factors for pulmonary embolism in patients with spinal injury.Methods:Literature on risk factors for pulmonary embolism after spinal injury was searched on CNKI, Wanfang database, VIP Chinese Science, PubMed, Embase, Cochrane Library, Up to Date databases from inception through November 2023. A Meta-analysis was performed with the software of RevMan 5.4 after two researchers screened the literature independently according to the inclusion and exclusion criteria, extracted the data and evaluated their quality. Correlations of gender, age, surgical duration, intervertebral disc fusion, body mass index, comorbidity, medicine prophylaxis, deep venous thrombosis (DVT) history, and length of hospital stay with the incidence of pulmonary embolism in patients with spinal injury were evaluated.Results:A total of 10 studies were enrolled, including 2 prospective cohort studies and 8 cross-sectional studies. The total sample size was 401 698 patients, with 525 in the pulmonary embolism group and 401 173 in the non-pulmonary embolism group. The Meta analysis showed that gender ( OR=1.59, 95% CI 1.20, 1.97), age ( OR=1.58, 95% CI 1.19, 2.10), surgical duration ( OR=2.56, 95% CI 1.84, 3.56), DVT history ( OR=15.84, 95% CI 1.88, 133.25) and length of hospital stay ( OR=1.08, 95% CI 1.07, 1.09) were statistically significantly correlated with the incidence of pulmonary embolism in patients with spinal injury ( P<0.01), while intervertebral fusion, body mass index, comorbidity, and medicine prophylaxis were not correlated with the incidence of pulmonary embolism ( P>0.05). Conclusion:Gender, age, surgical duration, DVT history and length of hospital stay are risk factors for pulmonary embolism in patients with spinal injury.

Objective:To investigate the clinical features and related risk factors of multi-drug resistant organism (MDRO) infection after liver transplantation, so as to guide clinical identification of high-risk patients and reduce the occurrence of MDRO infection.Methods:Of 187 patients undergoing liver transplantation in the First Affiliated Hospital of Nanjing Medical University from February 2019 to September 2020 were enrolled, including 150 males and 37 females, aged (50.6±9.6) years. Data related to MDRO infection were collected, and independent risk factors were identified using univariate analysis and multiple logistic regression analysis.Results:Among the 187 patients, MDRO infection occurred in 39, and 9 patient deaths were directly related to MDRO infection. Lung is the most common infection site, accounting for 82.1% (32/39) of MDRO infection. The most common pathogenic bacteria were Acinetobacter baumannii and Carbapenem-resistant enterobacteriaceae, accounting for 46.8%(36/77) and 41.7%(32/77) of MDRO infection, respectively. Multiple logistic regression analysis showed that postoperative mechanical ventilation ≥ 48 h ( OR=3.430, 95% CI: 1.124-10.467, P=0.030), intensive care unit (ICU) stay ≥7 d ( OR=9.013, 95% CI: 3.054-26.594, P<0.001) were independent risk factors of postoperative MDRO infection. Conclusions:Early removal of endotracheal intubation and discharge from ICU are important to reduce the risk of MDRO infection after liver transplantation.

Objective:To realize a fully automated synthesis of 11C-meta-hydroxyephedrine (mHED) and to perform imaging studies with it. Methods:11C-mHED was prepared by the 11CH 3-triflate method. The crude product was purified by semi-preparative high performance liquid chromatograph (HPLC) to obtain the final product. The radiochemical purity and specific activity were determined by radio-HPLC. The myocardial uptake and excretion process of the agent were monitored by microPET/CT imaging on 5 normal SD rats. The clinical imaging value was evaluated using PET/CT imaging in a patient (male, 42 years old) with myocardial infarction. Results:The automated synthesis of 11C-mHED was realized by a commercial synthesizer. The total synthesis time was about 30 min. The radiochemical yield was (15±2)% (non-decay corrected, n=10) and the radiochemical purity was greater than 98%. The specific activity was about 65 GBq/mmol. MicroPET/CT imaging in normal SD rats showed the myocardial uptake was highest at 10 min after the injection of imaging agent, and then the imaging agent was gradually excreted from the myocardium through the liver and gallbladder. PET/CT imaging of a patient with myocardial infarction showed an imaging agent defect near the apex in the inferior wall of the left ventricle, which was matched with results of ultrasound and electrocardiogram examination. Conclusions:11C-mHED can be successfully prepared automatically, with high radiochemical yield and specific activity. It can also highly concentrate in the myocardium, and the imaging effect with this agent is good in a patient with myocardial infarction.