[Objective] To investigate the differences in metabolomics between apheresis platelets stored at 4℃ and at 22℃ with agitation, aiming to provide a theoretical basis for the cold storage of apheresis platelets. [Methods] Samples were collected at four time points (d1, d5, d10, d15) for platelets stored at 4℃ (experimental group) and two time points (d1, d5) for platelets stored at 22℃ with agitation (control group). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was used to detect changes in platelet metabolome levels under different storage conditions. Platelet functional activity was assessed by thromboelastography (TEG) for maximum amplitude (MA) values and flow cytometry for CD62P activation rates. [Results] Metabolites in the glycolytic pathway, key metabolites in the tricarboxylic acid cycle (citrate, α-ketoglutarate), metabolites in the purine metabolism pathway (adenine, inosine monophosphate, guanine, etc.) and amino acid metabolites significantly decreased by d5 in the control group, whereas they remained stable in the experimental group. The content of fatty acid metabolites, such as prostaglandin G2, 13(S)-HOTrE, and linoleic acid, significantly increased in the control group. Statistically significant differences in MA values were observed between the two groups at d1 and d5 (P<0.05). However, in the experimental group, as the storage time extended, the MA values at d10 and d15 showed no significant difference compared to the control group at d5 (P>0.05). The CD62P activation rate between the two groups was statistically significant (P<0.05). Additionally, the CD62P activation rate of platelets in the 22℃ group increased rapidly from d1, while it rose gradually in the 4 ℃ group. [Conclusion] Platelets stored at 4 ℃ exhibit more stable metabolic activity and slower functional deterioration, which is beneficial for extending the effective storage period of platelets.

Objective:To compare the anticoagulant efficacy and safety between argatroban and heparin in patients with liver failure complicated with hepatic encephalopathy undergoing artificial liver treatment.Methods:A total of 207 patients with liver failure complicated with hepatic encephalopathy who received artificial liver treatment in the intensive care unit (ICU) of Wuxi No.5 People′s Hospital from January 2021 to October 2024 were enrolled, including 105 cases in the argatroban group and 102 cases in the heparin group. Changes in coagulation function, hemoglobin (Hb), platelet (PLT) count, and model for end-stage liver disease (MELD) score before and after artificial liver treatment were compared between the two groups. The formation of deep vein thrombosis in the lower extremities, coagulation in the extracorporeal circulation circuit and plasma separator, bleeding at the deep venous catheter site were compared between the two groups. The 28-day survival outcome of the patient were recorded. Two independent sample t-test, rank sum test, and chi-square test were used for statistical comparisons, and the Kaplan-Meier method and log-rank test were used to analyze the survival rate of patients. Results:There were no statistically significant differences in activated partial thromboplastin (APTT), international normalized ratio (INR), Hb and PLT count before and after artificial liver treatment in the argatroban group ( Z=-1.74, -1.80, -1.26 and -0.52, respectively, all P>0.05), while the MELD score after treatment was lower than that before treatment and the difference was statistically significant ( t=6.49, P<0.001). After artificial liver treatment, the APTT in the argatroban group was 47.10(42.65, 51.90) s, which was shorter than that in the heparin group (56.05(50.02, 63.00) s). The INR, Hb, and PLT count in the argatroban group were 2.00(1.65, 2.54), 98.00(88.00, 112.00) g/L, and 92.00(75.50, 106.00)×10 9/L, respectively, which were all higher than those in the heparin group, which were 1.56(1.22, 1.93) g/L, 90.50(80.00, 104.75) g/L, and 74.00(64.75, 99.50)×10 9/L, respectively. The differences were all statistically significant ( Z=-7.16, -5.28, -3.05 and -3.32, respectively, all P<0.05). There was no statistically significant difference in MELD scores between the two groups ( P=0.250). The incidence of coagulation in the extracorporeal circulation circuit and plasma separator and bleeding at the deep venous catheter site in the argatroban group was 5.71%(6/105) and 1.90%(2/105), respectively, which were both lower than those in the heparin group (14.71%(15/102) and 9.80%(10/102), respectively). The differences were both statistically significant ( χ2=4.59 and 5.91, respectively, both P<0.05). At the end of the 28-day follow-up, the mortality rates in the argatroban group and the heparin group were 22.9%(24/105) and 34.3%(35/102), respectively, and the difference was not statistically significant ( χ2=3.33, P=0.068). There was no statistically significant difference in the 28-day survival rate between the argatroban group and the heparin group ( χ2=2.09, P>0.05). Conclusions:Argatroban has a relatively minor impact on PLT count and Hb when it is used in artificial liver treatment for patients with liver failure complicated with hepatic encephalopathy. The incidence of coagulation in extracorporeal circulation circuits and plasma separators is low, and the risk of bleeding at the deep venous catheters is low. Argatroban is highly safe, which provides a new anticoagulation option for patients with a high risk of bleeding.

Objective:To explore the correlation and predictive value of the blood urea nitrogen to serum albumin ratio (BAR) in the development of sepsis among patients with acute-on-chronic liver failure (ACLF).Methods:A total of 410 patients diagnosed with ACLF who were admitted to Wuxi Fifth People′s Hospital between January 1st, 2020 and December 31st, 2024 were enrolled in this study. Demographic information, laboratory test indicators, and other clinical data were retrospectively analyzed. Participants were stratified into two groups using a 6∶4 allocation ratio, comprising a training set of 246 patients and a validation set of 164 patients, the clinical data of two groups were compared. Logistic regression was employed to evalute the influencing factors of sepsis during hospitalization in ACLF patients. Additionally, the predictive value of different factors for sepsis occurrence was evaluated using receiver-operating characteristic curve analysis. DeLong test was used to compare the area under the curve.Results:The comparison of baseline data between the training set and the validation set revealed no statistically significant differences (all P>0.05). A total of 197 sepsis cases were observed during the study period. Multivariate logistic regression analysis revealed that both BAR and the sequential organ failure assessment (SOFA) score were independent influencing factors for sepsis development in ACLF patients (odds ratio ( OR)=1.274, 95% confidence interval (95% CI) 1.075 to 1.510, P=0.005; OR=1.142, 95% CI 1.038 to 1.256, P=0.006). In the training set, the area under the curve (AUC) of BAR for predicting sepsis in ACLF patients was 0.802, which was superior to that of the SOFA score (AUC=0.706) ( Z=2.16, P=0.031). The validation set showed the predictive ability of BAR with an AUC of 0.726, which was superior to the SOFA score′s performance (AUC=0.606) ( Z=2.28, P=0.023). Conclusions:BAR could independently predict sepsis development in ACLF patients with significant prognostic value. BAR could be used as a clinically useful biomarker for sepsis risk stratification.

Objective:To analyze the efficacy and prognostic factors of fractionated stereotactic radiotherapy (FSRT) for patients with breast cancer brain metastases (BCBM).Methods:Medical records and follow-up data of BCBM patients who underwent FSRT in Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center and Shenzhen People's Hospital from August 2019 to May 2023 were collected. The R Studio platform of the R version 4.2.1 statistical software was applied to analyze patients' baseline characteristics, 1- and 2-year local brain control (LBC), overall survival (OS) and distant brain control (DBC) and corresponding median failure-free survival, draw survival curve using Kaplan-Meier method. Prognostic factors were screened by univariate analysis and multivariate analysis (Cox regression).Results:Cumulatively, 52 patients (163 metastases in total) had a median survival follow-up of 22.1 months, 83% were<60 years old. Molecular typing: 13 cases (25%) were positive for human epidermal growth factor receptor 2 (HER2+) / hormone receptor negative (HR-), 2 cases (4%) were luminal A, 26 cases (50%) were luminal B, and 11 cases (21%) were triple negative. The median number of brain metastases was 2 (range: 1 - 17). Follow-up outcomes: the median OS was 34.0 months, with 1- and 2-year OS rates of 85.6% and 65.4%, respectively; the median LBC was 20.6 months, with 1- and 2-year LBC rates of 79.2% and 45.2%, respectively; and the median DBC was 10.3 months, with 1- and 2-year DBC rates of 46.7% and 28.9%, respectively. During follow-up, 13 patients underwent salvage local therapy (10 FSRT); 5 developed radiation necrosis (1 symptomatic). Prognostic factor analysis: absence of extracranial organ metastases (compared with ≥3) was a protective factor for OS, P<0.05. For LBC, fewer (1 - 2) extracranial organ metastases (compared with ≥3), and single brain metastasis (compared with ≥2) were favorable prognostic factors , while N 3 staging upon initial diagnosis was a poor prognostic factor (all P<0.05). For DBC, brain metastasis after surgery was a good prognostic factor, while complicated with lung metastasis and asymptomatic brain metastasis at the first diagnosis were poor prognostic factors (all P<0.05). Conclusions:FSRT yields relatively good LBC and poor DBC for BCBM patients. A certain percentage of patients require salvage FSRT during follow-up, but OS is maintained acceptable and the radiation necrosis is tolerable. Among the prognostic factors, the absence of extracranial metastatic organs is a good prognostic factor for OS; patients with single brain metastasis, fewer extracranial metastatic organs, and non-N 3 staging upon initial diagnosis can obtain better LBC after FSRT.

Objective:To explore the correlation and predictive value of the blood urea nitrogen to serum albumin ratio (BAR) in the development of sepsis among patients with acute-on-chronic liver failure (ACLF).Methods:A total of 410 patients diagnosed with ACLF who were admitted to Wuxi Fifth People′s Hospital between January 1st, 2020 and December 31st, 2024 were enrolled in this study. Demographic information, laboratory test indicators, and other clinical data were retrospectively analyzed. Participants were stratified into two groups using a 6∶4 allocation ratio, comprising a training set of 246 patients and a validation set of 164 patients, the clinical data of two groups were compared. Logistic regression was employed to evalute the influencing factors of sepsis during hospitalization in ACLF patients. Additionally, the predictive value of different factors for sepsis occurrence was evaluated using receiver-operating characteristic curve analysis. DeLong test was used to compare the area under the curve.Results:The comparison of baseline data between the training set and the validation set revealed no statistically significant differences (all P>0.05). A total of 197 sepsis cases were observed during the study period. Multivariate logistic regression analysis revealed that both BAR and the sequential organ failure assessment (SOFA) score were independent influencing factors for sepsis development in ACLF patients (odds ratio ( OR)=1.274, 95% confidence interval (95% CI) 1.075 to 1.510, P=0.005; OR=1.142, 95% CI 1.038 to 1.256, P=0.006). In the training set, the area under the curve (AUC) of BAR for predicting sepsis in ACLF patients was 0.802, which was superior to that of the SOFA score (AUC=0.706) ( Z=2.16, P=0.031). The validation set showed the predictive ability of BAR with an AUC of 0.726, which was superior to the SOFA score′s performance (AUC=0.606) ( Z=2.28, P=0.023). Conclusions:BAR could independently predict sepsis development in ACLF patients with significant prognostic value. BAR could be used as a clinically useful biomarker for sepsis risk stratification.

Objective:To compare the anticoagulant efficacy and safety between argatroban and heparin in patients with liver failure complicated with hepatic encephalopathy undergoing artificial liver treatment.Methods:A total of 207 patients with liver failure complicated with hepatic encephalopathy who received artificial liver treatment in the intensive care unit (ICU) of Wuxi No.5 People′s Hospital from January 2021 to October 2024 were enrolled, including 105 cases in the argatroban group and 102 cases in the heparin group. Changes in coagulation function, hemoglobin (Hb), platelet (PLT) count, and model for end-stage liver disease (MELD) score before and after artificial liver treatment were compared between the two groups. The formation of deep vein thrombosis in the lower extremities, coagulation in the extracorporeal circulation circuit and plasma separator, bleeding at the deep venous catheter site were compared between the two groups. The 28-day survival outcome of the patient were recorded. Two independent sample t-test, rank sum test, and chi-square test were used for statistical comparisons, and the Kaplan-Meier method and log-rank test were used to analyze the survival rate of patients. Results:There were no statistically significant differences in activated partial thromboplastin (APTT), international normalized ratio (INR), Hb and PLT count before and after artificial liver treatment in the argatroban group ( Z=-1.74, -1.80, -1.26 and -0.52, respectively, all P>0.05), while the MELD score after treatment was lower than that before treatment and the difference was statistically significant ( t=6.49, P<0.001). After artificial liver treatment, the APTT in the argatroban group was 47.10(42.65, 51.90) s, which was shorter than that in the heparin group (56.05(50.02, 63.00) s). The INR, Hb, and PLT count in the argatroban group were 2.00(1.65, 2.54), 98.00(88.00, 112.00) g/L, and 92.00(75.50, 106.00)×10 9/L, respectively, which were all higher than those in the heparin group, which were 1.56(1.22, 1.93) g/L, 90.50(80.00, 104.75) g/L, and 74.00(64.75, 99.50)×10 9/L, respectively. The differences were all statistically significant ( Z=-7.16, -5.28, -3.05 and -3.32, respectively, all P<0.05). There was no statistically significant difference in MELD scores between the two groups ( P=0.250). The incidence of coagulation in the extracorporeal circulation circuit and plasma separator and bleeding at the deep venous catheter site in the argatroban group was 5.71%(6/105) and 1.90%(2/105), respectively, which were both lower than those in the heparin group (14.71%(15/102) and 9.80%(10/102), respectively). The differences were both statistically significant ( χ2=4.59 and 5.91, respectively, both P<0.05). At the end of the 28-day follow-up, the mortality rates in the argatroban group and the heparin group were 22.9%(24/105) and 34.3%(35/102), respectively, and the difference was not statistically significant ( χ2=3.33, P=0.068). There was no statistically significant difference in the 28-day survival rate between the argatroban group and the heparin group ( χ2=2.09, P>0.05). Conclusions:Argatroban has a relatively minor impact on PLT count and Hb when it is used in artificial liver treatment for patients with liver failure complicated with hepatic encephalopathy. The incidence of coagulation in extracorporeal circulation circuits and plasma separators is low, and the risk of bleeding at the deep venous catheters is low. Argatroban is highly safe, which provides a new anticoagulation option for patients with a high risk of bleeding.

Objective:To analyze the efficacy and prognostic factors of fractionated stereotactic radiotherapy (FSRT) for patients with breast cancer brain metastases (BCBM).Methods:Medical records and follow-up data of BCBM patients who underwent FSRT in Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center and Shenzhen People's Hospital from August 2019 to May 2023 were collected. The R Studio platform of the R version 4.2.1 statistical software was applied to analyze patients' baseline characteristics, 1- and 2-year local brain control (LBC), overall survival (OS) and distant brain control (DBC) and corresponding median failure-free survival, draw survival curve using Kaplan-Meier method. Prognostic factors were screened by univariate analysis and multivariate analysis (Cox regression).Results:Cumulatively, 52 patients (163 metastases in total) had a median survival follow-up of 22.1 months, 83% were<60 years old. Molecular typing: 13 cases (25%) were positive for human epidermal growth factor receptor 2 (HER2+) / hormone receptor negative (HR-), 2 cases (4%) were luminal A, 26 cases (50%) were luminal B, and 11 cases (21%) were triple negative. The median number of brain metastases was 2 (range: 1 - 17). Follow-up outcomes: the median OS was 34.0 months, with 1- and 2-year OS rates of 85.6% and 65.4%, respectively; the median LBC was 20.6 months, with 1- and 2-year LBC rates of 79.2% and 45.2%, respectively; and the median DBC was 10.3 months, with 1- and 2-year DBC rates of 46.7% and 28.9%, respectively. During follow-up, 13 patients underwent salvage local therapy (10 FSRT); 5 developed radiation necrosis (1 symptomatic). Prognostic factor analysis: absence of extracranial organ metastases (compared with ≥3) was a protective factor for OS, P<0.05. For LBC, fewer (1 - 2) extracranial organ metastases (compared with ≥3), and single brain metastasis (compared with ≥2) were favorable prognostic factors , while N 3 staging upon initial diagnosis was a poor prognostic factor (all P<0.05). For DBC, brain metastasis after surgery was a good prognostic factor, while complicated with lung metastasis and asymptomatic brain metastasis at the first diagnosis were poor prognostic factors (all P<0.05). Conclusions:FSRT yields relatively good LBC and poor DBC for BCBM patients. A certain percentage of patients require salvage FSRT during follow-up, but OS is maintained acceptable and the radiation necrosis is tolerable. Among the prognostic factors, the absence of extracranial metastatic organs is a good prognostic factor for OS; patients with single brain metastasis, fewer extracranial metastatic organs, and non-N 3 staging upon initial diagnosis can obtain better LBC after FSRT.

Deficient mismatch repair(dMMR)is currently recognized as a biomarker for predicting the efficacy of immune checkpoint inhib-itors(ICIs),and domestic and foreign guidelines recommend first-line immunotherapy for patients with solid dMMR tumors.For rectal can-cer,only 5%of patients are classified as dMMR/microsatellite instability-high(MSI-H),and most have"immune desert type"or mismatch re-pair proficient(pMMR)/microsatellite stabilization(MSS)diseases,which respond poorly to ICIs.Therefore,recently,the synergistic effect of immune drugs and neoadjuvant chemoradiotherapy has been the focus of basic and clinical research.An increasing number of clinical trials of phase Ⅱ/Ⅲ immuno-total neoadjuvant therapy(iTNT)have emerged,and the management of locally advanced rectal cancer(LARC)has begun to enter the non-operative treatment era.Furthermore,an increasing number of studies support the efficacy of neoadjuvant immun-otherapy in patients with dMMR/MSI-H LARC,which exempts such patients from surgery and chemoradiotherapy as follow-up treatment and results in a pivot in the treatment paradigm of a watch-and-wait strategy.Regarding the LARC with pMMR/MSS,the preliminary iTNT findings support ICIs as a shift from an initial posterior-line palliative scheme to a first-line selection strategy and the continuation of large-scale clinical trials.However,no definitive conclusion has been reached regarding the best iTNT application for LARC.Recent studies have shown that short-course radiotherapy and sequential neoadjuvant chemotherapy,combined with immunotherapy,can achieve good short-term outcomes.Finally,identifying other new biomarkers may facilitate the identification of patients with pMMR/MSS who are sensitive to immune drugs(especially for low rectal cancer).In the future,the treatment strategy of LARC should be combined with the stratification of clinical recurrence risk and patient willingness for organ retention to achieve stratified and accurate treatment.This article will review the re-lated research background,basic and clinical research progress and existing problems of iTNT in LARC.

Objective:To analyze the impact of baseline quantification of hepatitis B core antibody (qHBcAb) on prognosis of patients with hepatitis B virus (HBV) related acute-on-chronic liver failure (HBV-ACLF).Methods:A total of 91 HBV-ACLF patients (HBV-ACLF group), who admitted to Wuxi No.5 People′s Hospital from July 1, 2019 to December 30, 2021, were included in this study. Fifty chronic hepatitis B (CHB) patients (CHB group) and 50 chronic HBV carriers (HBV carrier group) were enrolled as controls. Baseline clinical data such as qHBcAb, blood routine examination biochemical, and coagulation indices, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA levels were recorded and analyzed retrospectively. The HBV-ACLF, HBsAg and HBV-DNA data were converted logarithmically. Patients were followed-up for 90 days. Cox regression was used to analyze the correlation between HBV-ACLF and survival outcome; survival rate was estimated by the Kaplan-Meier method; receiver operating characteristic (ROC) curve was used to evaluate the predictive value of baseline qHBcAb for the prognosis in patients with HBV-ACLF.Results:The baseline qHBcAb level in HBV-ACLF patients was (4.83±0.42) IU/ml, which was significantly higher than that in the CHB group [(4.59±0.54) IU/ml] and chronic HBV carrier group [(3.86±0.74) IU/ml] (all P<0.05). At the end of 90 days follow-up, 46 patients (50.55%) survived, and 45 patients (49.45%) died in the HBV-ACLF group. The baseline qHBcAb level was significantly higher in the survival group [(4.93±0.22) IU/ml] than in the death group [(4.70±0.52) IU/ml, P<0.01]. Significant differences were also found in the alpha fetoprotein, international normalized ratio, prothrombin activity, antithrombin Ⅲ activity, platelet, end-stage liver disease model score and hepatic encephalopathy complication between the two groups ( P<0.05). Cox regression analysis showed that the baseline qHBcAb was an independent risk factor affecting the 90-day survival of HBV-ACLF patients [hazard ratio=0.027,95% confidence interval ( CI) 0.001-0.696, P<0.05]. The area under the ROC curve of baseline qHBcAb level for predicting the 90-day survival outcome of HBV-ACLF patients was 0.639 (95% CI 0.525-0.752, P<0.05), with a cut-off value of 4.89 IU/ml. The cumulative survival rate of patients with baseline qHBcAb≥4.89 IU/ml was higher than that of patients with baseline qHBcAb<4.89 IU/ml ( P<0.05). Conclusions:Higher baseline qHBcAb level is associated with favorable outcome of HBV-ACLF patients and baseline qHBcAb may be used as a new biomarker to predict the clinical outcome of HBV-ACLF patients. HBV-ACLF patients with serum qHBcAb lower than 4.89 IU/ml face increased risk of short-term death.

Objective:To explore the therapeutic effect of multi-mode sequential combination of artificial liver in the treatment of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data of HBV-ACLF patients treated with artificial liver in Wuxi Fifth People′s Hospital from January 2018 to June 2021 were retrospectively analyzed. Eighty-six patients were divided into artificial liver multi-mode sequential combination therapy group (sequential combination group) and conventional treatment group. The cytokine level changes and model for end-stage liver disease (MELD) score were analyzed at 14 days of disease duration. The survival outcome and complications of artificial liver were analyzed after 30 days of follow-up. Two independent samples t test and chi-square test were used for statistical analysis. Cox regression analysis was used to analyze the risk factors of death, and Kaplan-Meier method was used to analyze the survival rate of patients. Results:A total of 86 patients were enrolled, including 48 patients in sequential combination group with the average number of artificial liver of 4.68 times/person, and 38 patients in conventional treatment group with the average number of artificial liver of 3.17 times/person. At 14 days of disease duration, interleukin (IL)-6, IL-8, interferon γ-inducible protein (IP)-10 level and MELD score in sequential combination group decreased significantly than those in the conventional treatment group ( t=3.80, 3.62, 4.95 and 1.11, respectively, all P<0.050). After 30 days of follow-up, 63 patients survived and 23 patients died. Cox regression analysis showed that baseline international normalized ratio (hazard ratio ( HR)=0.558, 95% confidence interval ( CI) 0.193 to 0.856, P=0.027), baseline antithrombin Ⅲ activity ( HR=0.876, 95% CI 0.824 to 0.932, P<0.001), artificial liver mode ( HR=0.819, 95% CI 0.236 to 0.992, P=0.005), spontaneous peritonitis ( HR=0.170, 95% CI 0.045 to 0.647, P=0.009) and hepatic encephalopathy ( HR=0.004, 95% CI 0.001 to 0.030, P<0.001) were independent influencing factors for 30-day survival outcome. The cumulative survival rate of sequential combination group was higher than that of conventional treatment group, and the difference was statistically significant ( χ2=5.45, P=0.020). There were no significant differences in the proportions of bleeding, deep vein thrombosis, heart rate and blood pressure instability between the two groups ( χ2=0.63, 1.20 and 0.54, respectively, all P>0.050). The platelet decline of patients in sequential combination group was slighter than that in conventional treatment group, and the difference was statistically significant ( t=-4.17, P=0.002). Conclusions:Multi-mode sequential combination therapy of artificial liver could eliminate cytokines and reduce MELD score more effectively in patients with HBV-ACLF, and prolong the survival time of patients and have little effect on platelet count.